bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for Host Cells as the Major Contributor of Lipids in the Intravacuolar Network of Toxoplasma-Infected Cells
Authors: Caffaro Carolina E. , Boothroyd John C.
Published: June 2011

The intracellular parasite
Toxoplasma gondii
develops inside a parasitophorous vacuole (PV) that derives from the host cell plasma membrane during invasion. Previous electron micrograph images have shown that the membrane of this vacuole undergoes an extraordinary remodeling with an extensive network of thin tubules and vesicles, the intravacuolar network (IVN), which fills the lumen of the PV. While dense granule proteins, secreted during and after invasion, are the main factors for the organization and tubulation of the network, little is known about the source of lipids used for this remodeling. By selectively labeling host cell or parasite membranes, we uncovered evidence that strongly supports the host cell as the primary, if not exclusive, source of lipids for parasite IVN remodeling. Fluorescence recovery after photobleaching (FRAP) microscopy experiments revealed that lipids are surprisingly dynamic within the parasitophorous vacuole and are continuously exchanged or replenished by the host cell. The results presented here suggest a new model for development of the parasitophorous vacuole whereby the host provides a continuous stream of lipids to support the growth and maturation of the PVM and IVN.
Protein Arginine Methylation in Parasitic Protozoa
Authors: Fisk John C. , Read Laurie K.
Published: June 2011

Protozoa constitute the earliest branch of the eukaryotic lineage, and several groups of protozoans are serious parasites of humans and other animals. Better understanding of biochemical pathways that are either in common with or divergent from those of higher eukaryotes is integral in the defense against these parasites. In yeast and humans, the posttranslational methylation of arginine residues in proteins affects myriad cellular processes, including transcription, RNA processing, DNA replication and repair, and signal transduction. The protein arginine methyltransferases (PRMTs) that catalyze these reactions, which are unique to the eukaryotic kingdom of organisms, first become evident in protozoa. In this review, we focus on the current understanding of arginine methylation in multiple species of parasitic protozoa, including
Trichomonas
,
Entamoeba
,
Toxoplasma
,
Plasmodium
, and
Trypanosoma
spp., and discuss how arginine methylation may play important and unique roles in each type of parasite. We mine available genomic and transcriptomic data to inventory the families of PRMTs in different parasites and the changes in their abundance during the life cycle. We further review the limited functional studies on the roles of arginine methylation in parasites, including epigenetic regulation in Apicomplexa and RNA processing in trypanosomes. Interestingly, each of the parasites considered herein has significantly differing sets of PRMTs, and we speculate on the importance of this diversity in aspects of parasite biology, such as differentiation and antigenic variation.
Genome Sequence of Listeria monocytogenes Scott A, a Clinical Isolate from a Food-Borne Listeriosis Outbreak
Authors: Briers Yves , Klumpp Jochen , Schuppler Markus , Loessner Martin J.
Published: June 2011

Listeria monocytogenes
is an opportunistic food-borne pathogen and the causative agent of listeriosis in animals and humans. We present the genome sequence of
Listeria monocytogenes
Scott A, a widely distributed and frequently used serovar 4b clinical isolate from the 1983 listeriosis outbreak in Massachusetts.
Genome Sequence of the 17β-Estradiol-Utilizing Bacterium Sphingomonas Strain KC8
Authors: Hu Anyi , He Jibing , Chu Kung-Hui , Yu Chang-Ping
Published: June 2011

Sphingomonas
strain KC8 is known for its ability to utilize 17
β
-estradiol, a natural estrogen and an environmental endocrine-disrupting compound, as the sole carbon and energy source. Here, we report the draft genome sequence of the strain KC8 (4,074,265 bp, with a GC content of 63.7%) and major findings from its annotation.
Complete Genome Sequence of the Plant Pathogen Ralstonia solanacearum Strain Po82
Authors: Xu Jin , Zheng Hua-jun , Liu Lei , Pan Zhe-chao , Prior Philippe , Tang Biao , Xu Jing-sheng , Zhang Hao , Tian Qian , Zhang Li-qing , Feng Jie
Published: June 2011

Ralstonia solanacearum
strain Po82, a phylotype IIB/sequevar 4 strain, was found to be pathogenic to both solanaceous plants and banana. Here, we report the complete genome sequence of Po82 and its comparison with seven published
R. solanacearum
genomes.
Integration of Rehabilitation and Acupuncture in the Treatment of a Professional Musician with Temporomandibular Joint Dysfunction
Authors: Hunter Emma K
Published: June 2011

This case study describes the use of acupuncture in a professional musician with myogenic temporomandibular dysfunction. The 3-year history of symptoms was associated with persistent episodic tension-type headaches. Acupuncture was used for trigger point release, primarily of the masticatory muscles, in conjunction with exercise therapy. After 8 weekly acupuncture sessions, the patient's pain had completely resloved, headaches had resolved and the Patient-Specific Functional Scale showed significant improvements.
2010 i2b2/VA challenge on concepts, assertions, and relations in clinical text
Authors: Uzuner Özlem , South Brett R , Shen Shuying , DuVall Scott L
Published: June 2011

The 2010 i2b2/VA Workshop on Natural Language Processing Challenges for Clinical Records presented three tasks: a concept extraction task focused on the extraction of medical concepts from patient reports; an assertion classification task focused on assigning assertion types for medical problem concepts; and a relation classification task focused on assigning relation types that hold between medical problems, tests, and treatments. i2b2 and the VA provided an annotated reference standard corpus for the three tasks. Using this reference standard, 22 systems were developed for concept extraction, 21 for assertion classification, and 16 for relation classification.

These systems showed that machine learning approaches could be augmented with rule-based systems to determine concepts, assertions, and relations. Depending on the task, the rule-based systems can either provide input for machine learning or post-process the output of machine learning. Ensembles of classifiers, information from unlabeled data, and external knowledge sources can help when the training data are inadequate.
A regionalised strategy for improving motor vehicle-related highway driver deaths using a weighted averages method
Authors: Kim Tad , Rivara Frederick P , Mozingo David W , Lottenberg Lawrence , Harris Zachary B , Casella George , Liu Huazhi , Moldawer Lyle L , Efron Philip A , Ang Darwin N
Published: June 2011

Objective

The state of Florida has some of the most dangerous highways in the USA. In 2006, Florida averaged 1.65 fatalities per 100 million vehicle miles travelled (VMT) compared with the national average of 1.42. A study was undertaken to find a method of identifying counties that contributed to the most driver fatalities after a motor vehicle collision (MVC). By regionalising interventions unique to this subset of counties, the use of resources would have the greatest potential of improving statewide driver death.

Methods

The Florida Highway Safety Motor Vehicle database 2000–2006 was used to calculate driver VMT-weighted deaths by county. A total of 3 468 326 motor vehicle crashes were evaluated. Counties that had driver death rates higher than the state average were sorted by a weighted averages method. Multivariate regression was used to calculate the likelihood of death for various risk factors.

Results

VMT-weighted death rates identified 12 out of 67 counties that contributed up to 50% of overall driver fatalities. These counties were primarily clustered in central and south Florida. The strongest independent risk factors for driver death attributable to MVC in these high-risk counties were alcohol/drug use, rural roads, speed limit ≥45 mph, adverse weather conditions, divided highways, vehicle type, vehicle defects and roadway location.

Conclusions

Using the weighted averages method, a small subset of counties contributing to the majority of statewide driver fatalities was identified. Regionalised interventions on specific risk factors in these counties may have the greatest impact on reducing driver-related MVC fatalities.
What does ‘respect for persons’ require? Attitudes and reported practices of genetics researchers in informing research participants about research
Authors: Miller Fiona Alice , Hayeems Robin Zoe , Li Li , Bytautas Jessica Peace
Published: June 2011

Background

It has been suggested that researchers are obliged to offer summary findings to research participants to demonstrate respect for persons, and that this may increase public trust in, and awareness of, the research enterprise. Yet little research explores researchers' attitudes and practices regarding the range of initiatives that might serve these ends.

Methods

Results of an international survey of 785 eligible authors of genetics research studies in autism or cystic fibrosis are reported.

Results

Of 343 researchers who completed the survey (44% response rate), the majority agreed that their team should (i) inform participants of summary findings (90.7%) and (ii) ensure they gain an awareness of developments in the field (86.9%). Additionally, the majority reported that in practice, their team (i) informs participants of summary findings (69.4%) and (ii) provides other types of relevant non-results information (eg, state of science in the field, opportunities for research participation) (67.9%).

Conclusion

Researchers endorsed the obligation of communicating with research participants by providing summary findings and other research-related information in equal measure. In light of these findings, it is suggested that while the provision of summary results may contribute to efforts to discharge the obligation of respect for persons, it may be neither a necessary nor a sufficient means to this end.
Mario Monicelli'sGrande Guerra: the right of living and the choice of dying
Authors: Gulino Matteo , Frati Giacomo , Vergallo Gianluca Montanari , Frati Paola
Published: June 2011

Monicelli's suicide has reawakened a political and legal dispute about the medical role in end-of-life decisions, allowing us to discuss medical, ethical, legal, religious and political debate in various paradigmatic conscious and unconscious cases of end-of-life decision. We analyse the uncertainty about the ‘a priori’ choice between different specific legislative systems, highlighting the need for a unifying model, dictated by the existing trust in the critical relationship between patient and doctor, whose primary mission should be not only ‘to cure’ but also ‘to care’.
Efficacy of endovascular surgery for ruptured aneurysms with vasospasm of the parent artery
Authors: Kurata Akira , Suzuki Sachio , Iwamoto Kazuhisa , Inukai Madoka , Nakahara Kuniaki , Satou Kimitoshi , Niki June , Sasaki Makoto , Fujii Kiyotaka , Kan Shiichi , Kitahara Takao
Published: June 2011

Introduction

In the presence of vasospasm it is recommended that surgical clipping for a ruptured aneurysm should be delayed until it disappears, but this may be associated with re-rupture of the aneurysm resulting in a poor outcome. The indications for endovascular coil embolization in such cases are discussed.

Methods

Since November 2002, endovascular coil embolization has been used in 18 consecutive patients with ruptured aneurysm with vasospasm of the parent artery ranging from 2 to 28 days (mean 9 days) after the initial subarachnoid hemorrhage. After successful obliteration of the aneurysm, a microcatheter preceded by a guidewire was introduced into the peripheral vessels with vasospasm of the A2 or M2 portions in order to release the vasospasm mechanically.

Results

Endovascular procedures were performed successfully in all but one of the cases (94%), resulting in complete occlusion in 14 of 17 patients and mild dilation of the vasospasm in all 17 patients without technical complications or re-rupture of the aneurysm. In the one case of failure because of a tortuous artery, surgical clipping was performed after disappearance of the vasospasm. Cerebral infarction occurred in four patients, but only one correlated with the distribution of catheterization and the neurological deficits had completely disappeared 3 months after the onset.

Conclusion

Catheterization of parent vessels in cases of vasospasm is safe for coiling and also mechanically releases vasospasm. Vasospasm of M2 and A2 segments can be treated with microcatheterization only.
Extracellular proton depression of peak and late Na+ current in the canine left ventricle
Authors: Murphy Lisa , Renodin Danielle , Antzelevitch Charles , Di Diego José M. , Cordeiro Jonathan M.
Published: June 2011

Cardiac ischemia reduces excitability in ventricular tissue. Acidosis (one component of ischemia) affects a number of ion currents. We examined the effects of extracellular acidosis (pH 6.6) on peak and late Na+ current ( INa) in canine ventricular cells. Epicardial and endocardial myocytes were isolated, and patch-clamp techniques were used to record INa. Action potential recordings from left ventricular wedges exposed to acidic Tyrode solution showed a widening of the QRS complex, indicating slowing of transmural conduction. In myocytes, exposure to acidic conditions resulted in a 17.3 ± 0.9% reduction in upstroke velocity. Analysis of fast INa showed that current density was similar in epicardial and endocardial cells at normal pH (68.1 ± 7.0 vs. 63.2 ± 7.1 pA/pF, respectively). Extracellular acidosis reduced the fast INa magnitude by 22.7% in epicardial cells and 23.1% in endocardial cells. In addition, a significant slowing of the decay (time constant) of fast INa was observed at pH 6.6. Acidosis did not affect steady-state inactivation of INa or recovery from inactivation. Analysis of late INa during a 500-ms pulse showed that the acidosis significantly reduced late INa at 250 and 500 ms into the pulse. Using action potential clamp techniques, application of an epicardial waveform resulted in a larger late INa compared with when an endocardial waveform was applied to the same cell. Acidosis caused a greater decrease in late INa when an epicardial waveform was applied. These results suggest acidosis reduces both peak and late INa in both cell types and contributes to the depression in cardiac excitability observed under ischemic conditions.
A new model of congestive heart failure in rats
Authors: Chen Jiqiu , Chemaly Elie R. , Liang Li Fan , LaRocca Thomas J. , Yaniz-Galende Elisa , Hajjar Roger J.
Published: June 2011

Current rodent models of ischemia/infarct or pressure-volume overload are not fully representative of human heart failure. We developed a new model of congestive heart failure (CHF) with both ischemic and stress injuries combined with fibrosis in the remote myocardium. Sprague-Dawley male rats were used. Ascending aortic banding (Ab) was performed to induce hypertrophy. Two months post-Ab, ischemia-reperfusion (I/R) injury was induced by ligating the left anterior descending (LAD) artery for 30 min. Permanent LAD ligation served as positive controls. A debanding (DeAb) procedure was performed after Ab or Ab + I/R to restore left ventricular (LV) loading properties. Cardiac function was assessed by echocardiography and in vivo hemodynamic analysis. Myocardial infarction (MI) size and myocardial fibrosis were assessed. LV hypertrophy was observed 4 mo post-Ab; however, systolic function was preserved. LV hypertrophy regressed within 1 mo after DeAb. I/R for 2 mo induced a small to moderate MI with mild impairment of LV function. Permanent LAD ligation for 2 mo induced large MI and significant cardiac dysfunction. Ab for 2 mo followed by I/R for 2 mo (Ab + I/R) resulted in moderate MI with significantly reduced ejection fraction (EF). DeAb post Ab + I/R to reduce afterload could not restore cardiac function. Perivascular fibrosis in remote myocardium after Ab + I/R + DeAb was associated with decreased cardiac function. We conclude that Ab plus I/R injury with aortic DeAb represents a novel model of CHF with increased fibrosis in remote myocardium. This model will allow the investigation of vascular and fibrotic mechanisms in CHF characterized by low EF, dilated LV, moderate infarction, near-normal aortic diameter, and reperfused coronary arteries.
Sex differences and the effects of ovariectomy on the β-adrenergic contractile response
Authors: McIntosh Victoria J. , Chandrasekera P. Charukeshi , Lasley Robert D.
Published: June 2011

The presence of sex differences in myocardial β-adrenergic responsiveness is controversial, and limited studies have addressed the mechanism underlying these differences. Studies were performed using isolated perfused hearts from male, intact female and ovariectomized female mice to investigate sex differences and the effects of ovarian hormone withdrawal on β-adrenergic receptor function. Female hearts exhibited blunted contractile responses to the β-adrenergic receptor agonist isoproterenol (ISO) compared with males but not ovariectomized females. There were no sex differences in β1-adrenergic receptor gene or protein expression. To investigate the role of adenylyl cyclase, phosphodiesterase, and the cAMP-signaling cascade in generating sex differences in the β-adrenergic contractile response, dose-response studies were performed in isolated perfused male and female hearts using forskolin, 3-isobutyl-1-methylxanthine (IBMX), and 8-(4-chlorophenylthio)adenosine 3′,5′-cyclic monophosphate (CPT-cAMP). Males showed a modestly enhanced contractile response to forskolin at 300 nM and 5 μM compared with females, but there were no sex differences in the response to IBMX or CPT-cAMP. The role of the A1 adenosine receptor (A1AR) in antagonizing the β-adrenergic contractile response was investigated using both the A1AR agonist 2-chloro- N6-cyclopentyl-adenosine and A1AR knockout (KO) mice. Intact females showed an enhanced A1AR anti-adrenergic effect compared with males and ovariectomized females. The β-adrenergic contractile response was potentiated in both male and female A1ARKO hearts, with sex differences no longer present above 1 nM ISO. The β-adrenergic contractile response is greater in male hearts than females, and minor differences in the action of adenylyl cyclase or the A1AR may contribute to these sex differences.
Prolonged QT interval and lipid alterations beyond β-oxidation in very long-chain acyl-CoA dehydrogenase null mouse hearts
Authors: Gélinas Roselle , Thompson-Legault Julie , Bouchard Bertrand , Daneault Caroline , Mansour Asmaa , Gillis Marc-Antoine , Charron Guy , Gavino Victor , Labarthe François , Des Rosiers Christine
Published: June 2011

Patients with very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency frequently present cardiomyopathy and heartbeat disorders. However, the underlying factors, which may be of cardiac or extra cardiac origins, remain to be elucidated. In this study, we tested for metabolic and functional alterations in the heart from 3- and 7-mo-old VLCAD null mice and their littermate counterparts, using validated experimental paradigms, namely, 1) ex vivo perfusion in working mode, with concomitant evaluation of myocardial contractility and metabolic fluxes using13C-labeled substrates under various conditions; as well as 2) in vivo targeted lipidomics, gene expression analysis as well as electrocardiogram monitoring by telemetry in mice fed various diets. Unexpectedly, when perfused ex vivo, working VLCAD null mouse hearts maintained values similar to those of the controls for functional parameters and for the contribution of exogenous palmitate to β-oxidation (energy production), even at high palmitate concentration (1 mM) and increased energy demand (with 1 μM epinephrine) or after fasting. However, in vivo, these hearts displayed a prolonged rate-corrected QT (QTc) interval under all conditions examined, as well as the following lipid alterations: 1) age- and condition-dependent accumulation of triglycerides, and 2) 20% lower docosahexaenoic acid (an omega-3 polyunsaturated fatty acid) in membrane phospholipids. The latter was independent of liver but affected by feeding a diet enriched in saturated fat (exacerbated) or fish oil (attenuated). Our finding of a longer QTc interval in VLCAD null mice appears to be most relevant given that such condition increases the risk of sudden cardiac death.
Challenges for Quality Primary Education in Papua New Guinea—A Case Study
Authors: Rena Ravinder
Published: June 2011

There is an urgent need to reform the educational system to achieve universal primary education in Papua New Guinea (PNG). Even after 35 years of independence, PNG has been struggling to educate an estimated 2 million elementary- and primary-aged children and faces numerous challenges in providing Education for All (EFA). This study was conducted in four primary schools of Buma Yong area of Lae district of Morobe Province, PNG. The study revealed that the quality of education has been deteriorated over the past few decades. Many schools in PNG do not have classrooms, teachers, and basic facilities. As a result, the children are losing interest in going to school. The children dropped out of school so as to assist their families in the household and agricultural activities. It also reveals that the dropout rate of girls is more than that of the boys due to the gender disparity in the country. The study recommended that budgetary allocations should be increased so as to improve the infrastructural facilities and encourage the children to attend primary school and thus achieve the Millennium Development Goal/Education For All in PNG.
Effect of Thinning and Harvest Type on Storage and Losses of Phosphorous inPinus taedaL. Plantations in Subtropical Argentina
Authors: Martiarena Rodolfo Andrés , Frangi Jorge Luis , Pinazo Martín Alcides , Von Wallis Alejandra , Antonio Fernández Roberto
Published: June 2011

The aim of this study was to evaluate the effect of thinning intensity and different harvest types on ecosystem P conservation in 20-year-oldPinus taedaplantation ecosystems at Misiones province, Argentina. The plantation was established in 1985, thinned at three intensities—0, 33, and 66% of basal area of control plots removed by thinning—and harvested in 2005. The nutrient content at harvest was determined for tree, shrub, and herb layers, the forest floor and upper mineral soil. Two harvest types were simulated: stem only and whole tree. Total P content was 56.8, 46.8, and 38.6 kg· ha−1for 0, 33, and 66% thinning, respectively. Total P exported by harvest was different among treatments, the highest at 0% thinning treatment. Phosphorus stability index values indicated that the P most conservative management option is 66% thinning, harvest of stem only and retention of forest floor, understory, and harvest residues.
Regulation of Cancer Stem Cells by Cytokine Networks: Attacking Cancer's Inflammatory Roots
Authors: Korkaya Hasan , Liu Suling , Wicha Max S.
Published: June 2011

There is substantial evidence that many human cancers are driven by a subpopulation of cells that display stem cell properties. These cancer stem cells (CSC) may also contribute to metastasis and treatment resistance. Furthermore, just as normal stem cells are regulated by their microenvironment, or niche, CSCs interact with and in turn are regulated by cells in the tumor microenvironment. These interactions involve inflammatory cytokines, such as interleukin (IL)-1, IL-6, and IL-8, which in turn activate Stat3/NF-κB pathways in both tumor and stromal cells. Activation of these pathways stimulates further cytokine production, generating positive feedback loops that in turn drive CSC self-renewal. These cytokine loops and the pathways they regulate resemble those activated during chronic inflammation and wound healing, and may contribute to the known link between inflammation and cancer. Inhibitors of these cytokines and their receptors have been developed as anti-inflammatory agents. By blocking signals from the tumor microenvironment, these agents have the potential to target CSCs. Future clinical trials using these compounds will be needed to determine whether targeting the CSC population has clinical benefit. Clin Cancer Res; 17(19); 6125–9. ©2011 AACR.
mTOR Kinase Inhibition Causes Feedback-Dependent Biphasic Regulation of AKT Signaling
Authors: Rodrik-Outmezguine Vanessa S. , Chandarlapaty Sarat , Pagano Nen C. , Poulikakos Poulikos I. , Scaltriti Maurizio , Moskatel Elizabeth , Baselga José , Guichard Sylvie , Rosen Neal
Published: June 2011

mTOR kinase inhibitors block mTORC1 and mTORC2 and thus do not cause the mTORC2 activation of AKT observed with rapamycin. We now show, however, that these drugs have a biphasic effect on AKT. Inhibition of mTORC2 leads to AKT serine 473 (S473) dephosphorylation and a rapid but transient inhibition of AKT T308 phosphorylation and AKT signaling. However, inhibition of mTOR kinase also relieves feedback inhibition of receptor tyrosine kinases (RTK), leading to subsequent phosphoinositide 3-kinase activation and rephosphorylation of AKT T308 sufficient to reactivate AKT activity and signaling. Thus, catalytic inhibition of mTOR kinase leads to a new steady state characterized by profound suppression of mTORC1 and accumulation of activated AKT phosphorylated on T308, but not S473. Combined inhibition of mTOR kinase and the induced RTKs fully abolishes AKT signaling and results in substantial cell death and tumor regression in vivo. These findings reveal the adaptive capabilities of oncogenic signaling networks and the limitations of monotherapy for inhibiting feedback-regulated pathways.

Significance: The results of this study show the adaptive capabilities of oncogenic signaling networks, as AKT signaling becomes reactivated through a feedback-induced AKT species phosphorylated on T308 but lacking S473. The addition of RTK inhibitors can prevent this reactivation of AKT signaling and cause profound cell death and tumor regression in vivo, highlighting the possible need for combinatorial approaches to block feedback-regulated pathways. Cancer Discovery; 1(3); 248–59. © 2011 AACR.

Read the Commentary on this article by Keniry and Parsons, p. 203

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Management of Vagal Paragangliomas Including Application of Internal Carotid Artery Stenting
Authors: Shin Seung-Ho , Piazza Paolo , De Donato Giuseppe , Sivalingam Shailendra , Lauda Lorenzo , Vitullo Francesca , Sanna Mario
Published: June 2011

Background: The primary treatment of vagal paraganglioma (VP) includes ‘wait and scan’, surgery and radiotherapy. Objectives: To present the clinical findings, surgical treatment including application of internal carotid artery (ICA) stenting to facilitate surgery, and complications, as well as to review the literature and to discuss the decision-making process in the management of VP cases based on our experience and the literature. Design: A retrospective case review of 22 cases with VP. Setting: Quaternary neurotologic and skull base referral center. Material and Methods: The retrospective chart review identified 22 patients presenting with VP. Our indication for surgery was VP in younger patients, irrespective of the existence of vocal cord paralysis. Preoperative endovascular management of the ICA included permanent balloon occlusion (PBO) and stenting. The transcervical approach and the infratemporal fossa approach type A (ITFA) were used. Results: Fifteen cases had multicentric paragangliomas, 5 cases bilateral tumors, 3 cases a genetic mutation, and 2 cases a positive family history. The most common symptoms were hoarseness, tinnitus and hearing loss. The surgical approaches commonly employed for excision were the transcervical approach (9 cases) and the ITFA (12 cases), whereas 1 case did not have surgery. Three cases had PBO and 7 had intracarotid stent insertion. Gross total removal was achieved in 19 cases, and 1 case had a recurrence. Eighteen cases had no dysphagia or were well compensated after surgery. There were no significant complications noted in our series. Conclusions: In younger patients with VP, surgery should be recommended. The proper preoperative endovascular intervention and surgical approach facilitates gross total tumor removal. In the management of bilateral or familial paragangliomas, careful and appropriate decision making is essential.
A Computer Model of Normal Conduction in the Human Atria
Authors: David M. Harrild, Craig S. Henriquez ;
Published: June 2011

Abstract
—Although considerable progress has been made in understanding the process of wavefront propagation and arrhythmogenesis in human atria, technical concerns and issues of patient safety have limited experimental investigations. The present work describes a finite volume–based computer model of human atrial activation and current flow to complement these studies. Unlike previous representations, the model is three-dimensional, incorporating both the left and right atria and the major muscle bundles of the atria, including the crista terminalis, pectinate muscles, limbus of the fossa ovalis, and Bachmann’s bundle. The bundles are represented as anisotropic structures with fiber directions aligned with the bundle axes. Conductivities are assigned to the model to give realistic local conduction velocities within the bundles and bulk tissue. Results from simulations demonstrate the role of the bundles in a normal sinus rhythm and also reveal the patterns of activation in the septum, where experimental mapping has been extremely challenging. To validate the model, the simulated normal activation sequence and conduction velocities at various locations are compared with experimental observations and data. The model is also used to investigate paced activation, and a mechanism of the relative lengthening of left versus right stimulation is presented. Owing to both the realistic geometry and the bundle structures, the model can be used for further analysis of the normal activation sequence and to examine abnormal conduction, including flutter. The full text of this article is available at http://www.circresaha.org.
Acute and Chronic Effects of Epicardial Radiofrequency Applications Delivered on Epicardial Coronary Arteries
Authors: Viles-Gonzalez Juan F. , de Castro Miranda Reynaldo , Scanavacca Mauricio , Sosa Eduardo , d'Avila Andre
Published: June 2011

Background—

Epicardial coronary injury is by far the most feared complication of epicardial ablation. Little information is available regarding the chronic effects of delivering radiofrequency in the vicinity of large coronary vessels, and the long-term impact of this approach for mapping and ablation on epicardial vessel integrity is poorly understood. Therefore, the aim of this study was to characterize the acute and chronic histopathologic changes produced by in vivo epicardial pulses of radiofrequency ablation on coronary artery of porcine hearts.

Methods and Results—

Seven pigs underwent a left thoracotomy. The catheter was sutured adjacent to the left anterior descending artery and left circumflex artery, and 20 pulses of radiofrequency energy were applied. Radiofrequency lesions located no more than 1 mm of the vessel were used for this analysis. Three animals were euthanized 20 days (acute phase) after the procedure and 4 animals after 70 days (chronic phase). The following parameters were obtained in each vessel analyzed: (1) internal and external perimeter; (2) vessel wall thickness; (3) tunica media thickness, and (4) tunica intima thickness. The presence of adipose tissue around the coronary arteries, the distance between the artery and the epicardium, and the anatomic relationship of the artery with the coronary vein was also documented for each section. Sixteen of 20 (80%) sections analyzed, showed intimal thickening with a mean of 0.18±0.14 mm compared with 0.13±0.16 mm in the acute phase (
P
=0.331). The mean tunica media thickness was 0.25±0.10 mm in the chronic phase animals compared with 0.18±0.03 mm in the acute phase animals (
P
=0.021). A clear protective effect of pericardial fat and coronary veins was also present. A positive correlation between depth of radiofrequency lesion and the degree of vessel injury expressed as intimal and media thickening (
P
=0.001) was present. A negative correlation was identified (
r
=−0.83;
P
=0.002) between intimal thickening and distance between epicardium and coronary artery.

Conclusions—

In this porcine model of in vivo epicardial radiofrequency ablation in proximity to coronary arteries leads to acute and chronic histopathologic changes characterized by tunica intima and media thickening, with replacement of smooth muscle cells with extracellular matrix, but no significant stenosis was observed up to 70 days after the ablation. The absence of acute coronary occlusion or injury does not preclude subsequent significant arterial damage, which frequently occurs when epicardial radiofrequency applications are delivered in close vicinity to the vessels.
Multi-Analyte Profiling Reveals Matrix Metalloproteinase-9 and Monocyte Chemotactic Protein-1 as Plasma Biomarkers of Cardiac Aging
Authors: Chiao Ying Ann , Dai Qiuxia , Zhang Jianhua , Lin Jing , Lopez Elizabeth F. , Ahuja Seema S. , Chou Youn-Min , Lindsey Merry L. , Jin Yu-Fang
Published: June 2011

Background—

We have previously shown that cardiac sarcopenia occurs with age in C57/BL6J mice. However, underlying mechanisms and plasma biomarkers of cardiac aging have not been identified. Accordingly, the objective of this study was to identify and evaluate plasma biomarkers that reflect cardiac aging phenotypes.

Methods and Results—

Plasma from adult (7.5±0.5 months old, n=27) and senescent (31.7±0.5 months old, n=25) C57/BL6J mice was collected, and levels of 69 markers were measured by multi-analyte profiling. Of these, 26 analytes were significantly increased and 3 were significantly decreased in the senescent group compared with the adult group. The majority of analytes that increased in the senescent group were inflammatory markers associated with macrophage functions, including matrix metalloproteinase-9 (MMP-9) and monocyte chemotactic protein-1 (MCP-1/CCL-2). Immunoblotting (n=12/group) showed higher MMP-9 and MCP-1 levels in the left ventricle (LV) of senescent mice (
P
<0.05), and their expression levels in the LV correlated with plasma levels (ρ=0.50 for MMP-9 and ρ =0.62 for MCP1,
P
<0.05). Further, increased plasma MCP-1 and MMP-9 levels correlated with the increase in end-diastolic dimensions that occurs with senescence. Immunohistochemistry (n=3/group) for Mac-3, a macrophage marker, showed increased macrophage densities in the senescent LV, and dual-labeling immunohistochemistry of Mac-3 and MMP-9 revealed robust colocalization of MMP-9 to the macrophages in the senescent LV sections, indicating that the macrophage is a major contributor of MMP-9 in the senescent LV.

Conclusions—

Our results suggest that MCP-1 and MMP-9 are potential plasma markers for cardiac aging and that augmented MCP-1 and MMP-9 levels and macrophage content in the LV could provide an underlying inflammatory mechanism of cardiac aging.
Paraoxonase-1 Q192R Polymorphism and Antiplatelet Effects of Clopidogrel in Patients Undergoing Elective Coronary Stent Placement
Authors: Trenk Dietmar , Hochholzer Willibald , Fromm Martin F. , Zolk Oliver , Valina Christian M. , Stratz Christian , Neumann Franz-Josef
Published: June 2011

Background—

Recently published data indicate that the paraoxonase-1 (
PON1
) Q192R genotype—and not as previously shown activity of cytochrome P450 (CYP) 2C19—is the major determinant of metabolic bioactivation of clopidogrel and thereby variability of antiplatelet effect of clopidogrel. We sought to investigate whether the
PON1
Q192R gene polymorphism affects platelet reactivity in patients undergoing elective coronary stent placement.

Methods and Results—

The study included 760 consecutive patients undergoing elective coronary stent placement after loading with clopidogrel 600 mg. Platelet function was assessed by adenosine diphosphate-induced (ADP 5 and 20 μmol/L) platelet aggregation and by flow-cytometric analysis of platelet surface protein expression before clopidogrel, at the time of coronary stent placement, and before discharge after coronary stent placement.
PON1
Q192R genotype [NM_000446.5:c.575A>G single nucleotide polymorphism (rs662)] was analyzed by TaqMan polymerase chain reaction. Residual platelet aggregation (ADP 5 μmol/L) at predischarge was 8.0% (3.0% to 17.0%) [median (interquartile range)] in
PON1
QQ192 patients (n=384), 8.0% (3.0% to 15.0%) in
PON1
QR192 (n=304), and 11.0% (3.0% to 18.0%) in
PON1
RR192 (n=72;
P
=0.603). By multivariable linear regression, residual platelet aggregation was not associated with
PON1
QQ192/QR192 (partial η
2
<0.001,
P
=0.728) but with
CYP2C19*2
loss-of-function allele (partial η
2
=0.045,
P
<0.001) as well as any
CYP2C19*17
gain-of-function allele (partial η
2
=0.012,
P
=0.004). All other platelet assays also showed no significant association between
PON1
Q192R genotype and antiplatelet effect of clopidogrel. The 1-year incidence of death and myocardial infarction did not differ between
PON1
Q192R genotypes.

Conclusions—

On-treatment platelet reactivity in patients undergoing coronary stent placement after loading with clopidogrel 600 mg was not associated with
PON1
Q192R genotype.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00457236.
A Nation of Cities: The Federal Government and the Shape of the American Metropolis
Authors: Jackson Kenneth T.
Published: June 2011

In the almost sixty-five years since the end of World War II, governments at the federal, state, and local levels have played a major role in reducing the economic viability of cities in the United States. The 2008 election represents a possible turning point in federal policy. This article suggests that loosening restrictions on immigration, encouraging higher urban densities, reducing dependence on foreign oil, restoring infrastructure to a state of good repair, increasing the affordable housing stock, improving public safety, and reimagining new roles for Rust Belt cities should be at the top of a new agenda for urban America.
How Should Suburbs Help Their Central Cities? Growth- and Welfare-Enhancing Intrametropolitan Fiscal Distributions
Authors: Haughwout Andrew F. , Inman Robert P.
Published: June 2011

Cities are the location of the great majority of economic activity in the United States and produce a disproportionate share of output. It is thus critical for the economy’s long-term growth that cities operate efficiently. In this article, the authors review the basic determinants of output growth, with a focus on productivity growth in cities. The authors then explore the effects of a particular distortion in politically fragmented metropolitan areas. After documenting the interdependence of the suburbs and central city of a metropolitan area, the authors develop a model that embodies many of the empirically verified aspects, including agglomeration economies and public goods. After calibrating the model to outcomes for Philadelphia, the authors use it to simulate various policy changes. The authors conclude that, under the model, some kinds of fiscal redistributions can provide benefits in both cities and suburbs.
Cities Today: A New Frontier for Major Developments
Authors: Sassen Saskia
Published: June 2011

The article examines several major structural trends contributing to the shift from the Keynesian routinized city to the strategic city that begins to emerge in the 1980s. Among the trends examined is the growth of the firm-to-firm economy, which includes corporate and industrial services as well as “urban manufacturing.” These kinds of services tend to be produced in cities, even when the firms being served are nonurban, such as mines, steel plants, or large factories. A second key, and counterintuitive, trend is the ongoing importance of spatial centrality for our most advanced economic sectors. The more globalized and digitized a sector becomes, the more its firms suffer from incomplete knowledge about their markets. Urban centrality enables the making of what the author calls urban knowledge capital: a collective production that is more than the sum of the knowledge of the professionals and the firms present in a city.
Transport Infrastructure and Global Competitiveness: Balancing Mobility and Livability
Authors: Cervero Robert
Published: June 2011

In the United States, public infrastructure has been a necessary, though not sufficient, catalyst to economic growth and expansion, particularly in urban areas. However, infrastructure investments, and particularly highway construction, absent much in the way of proactive planning and farsighted land-use management, have for the most part also been sprawl-inducing. This article argues for carving a new relationship between public infrastructure and cities that balances the goals of economic productivity and community place-making. Often considered to be in conflict, they need not be. Experiences in San Francisco and Seoul show that the replacement of elevated freeways with greenways, boulevards, and public transit can improve neighborhood quality and increase land values. In Hong Kong, the aggressive application of value-capture strategies such as air-rights leasing with enhanced urban design increased economic rates of return.
Ethno-Racial Composition and College Preference: Revisiting the Perpetuation of Segregation Hypothesis
Authors: Butler Donnell
Published: June 2011

Braddock’s perpetuation hypothesis argues that racial segregation is self-perpetuated over the life cycle and across institutional settings. Studies examining the relationship between segregation and college choice consistently show that black students who attend segregated schools are more likely to choose predominantly black colleges over predominantly white colleges. This study extends previous research by considering not only blacks but also Hispanics, Asians, and whites. Consistent with Braddock’s claim, results show a positive association between the ethno-racial composition of schools and first college preference for all demographic groups considered. However, this association disappears for blacks and Hispanics after controlling for the ethno-racial composition of the nearest two- and four-year colleges. These findings indicate that geographic context better explains the perpetuation of segregation than same-group preferences.
Minority Higher Education Pipeline: Consequences of Changes in College Admissions Policy in Texas
Authors: Harris Angel , Tienda Marta
Published: June 2011

The authors uses administrative data for the two most selective Texas public institutions to examine the application, admission, and enrollment consequences of rescinding affirmative action and implementing the top 10 percent admission regime. The authors simulate the gains and losses associated with each policy regime and those from assigning minorities the corresponding rates for white students. Challenging popular claims that the Top Ten Percent Law restored diversification of Texas’s public flagships, analyses that consider both changes in the size of high school graduation cohorts and institutional carrying capacity show that the uniform admission regime did not restore Hispanic and black representation at the University of Texas at Austin and Texas A&M even after four years. Simulations of gains and losses for Hispanics and blacks at each stage of the college pipeline across admission regimes confirm that affirmative action is the most efficient policy to diversify college campuses, even in highly segregated states like Texas.
Race and Gender Differences in College Major Choice
Authors: Dickson Lisa
Published: June 2011

College major choice varies substantially by gender, race, and ethnicity among college graduates. This study investigates whether these differences are present at the start of the college career and whether they can be explained by variation in academic preparation. It estimates a multinomial logit to evaluate whether students of similar academic backgrounds make similar college major choices at the start of their college career. The results demonstrate that significant differences by gender, race, and ethnicity persist in initial college major choice even after controlling for the Scholastic Aptitude Test (SAT) score of the student and the high school class rank of the student. Gender differences in major choice are much larger than racial and ethnic disparities. Furthermore, women are significantly more likely to switch away from an initial major in engineering than are white men.
Differences in College Major Choice by Citizenship Status
Authors: Nores Milagros
Published: June 2011

Studies about college majors largely ignore non-citizen or immigrant populations. Using the administrative data from two public universities in Texas, the author examine students’ major choices by citizen status. In the context of legislation providing in-state tuition access for undocumented students (H.B. 1403, effective 2001), the author tests the effects of the policy on students’ choices of major. Foreign-born populations have a higher propensity to select majors in Science, Engineering and Math (SEM) and a lower propensity to enroll in social sciences than citizens. Domestic students exhibit variable propensities to opt for SEMs, depending on their race. There is evidence of behavioral changes pre— to post—H.B. 1403, with foreign-born populations shifting away from high-return majors.
Race and Ethnic Differences in College Achievement: Does High School Attended Matter?
Authors: Fletcher Jason , Tienda Marta
Published: June 2011

Using ten years of enrollment data at four Texas public universities, the authors examine whether, to what extent, and in what ways high school attended contributes to racial and ethnic differences in college achievement. As with previous studies, the authors show that controlling for class rank and test scores shrinks, but does not eliminate, sizable racial differences in college achievement. Fixed-effects models that take into account differences across high schools that minority and nonminority youth attend largely eliminate, and often reverse, black-white and Hispanic-white gaps in several college outcomes. The results, which are quite robust across universities of varying selectivity, illustrate how high school quality foments race and ethnic inequality in college performance.
Why Are Men Falling Behind? Gender Gaps in College Performance and Persistence
Authors: Conger Dylan , Long Mark C.
Published: June 2011

This article examines the male disadvantage in grade point average, credits earned, and persistence in college. Using data on enrollees in Florida and Texas four-year colleges to decompose gender differentials in the first semester, changes in the differentials between semesters, and persistence through college, we find that males earn lower GPAs and credits in their first semester of college largely because they arrive with lower high school grades. After the first semester, males fall further behind their female counterparts in grades and credits. Females’ better high school grades explain some of the widened gender disparity in performance but differences in college course-taking and majors also explain gender gaps in credits, grades, persistence, and graduation.