bluuebunny/crossref_metadata_2025 huggingface dataset:
Bilateral Subthalamic Deep Brain Stimulation after Bilateral Pallidal Deep Brain Stimulation for Parkinson’s Disease
Authors: Deogaonkar Milind , Monsalve Guillermo A. , Scott Jenera , Ahmed Anwar , Rezai Ali
Published: February 2011

Background/Objective: Globus pallidus internus (GPi) and subthalamic nucleus (STN) have successfully been targeted independently for deep brain stimulator (DBS) placement in medically intractable Parkinson’s disease (PD). Bilateral implantation of STN DBS in a patient with preexisting, functioning GPi DBS to specifically treat motor fluctuations is, to our knowledge, yet unreported. Clinical Presentation: We present a case of PD who had well-placed bilateral GPi DBS that controlled dyskinesia effectively and improved the motor symptoms like rigidity and akinesia. It did not improve her motor fluctuations and failed to reduce her medications. Methods: We implanted bilateral STN DBS, which improved her ‘on’ time, reduced her medications and improved her motor scores. Results/Conclusion: In this report we discuss the rationale, technical issues, programming nuances and outcome in a patient with preexisting bilateral GPi DBS who was implanted with bilateral STN DBS.
Uraemia Progression in Chronic Kidney Disease Stages 3–5 Is Not Constant
Authors: Heaf James Goya , Mortensen Leif Spange
Published: February 2011

Introduction: Chronic kidney disease (CKD) is a progressive disease leading to loss of glomerular filtration rate (ΔGFR, measured in ml/min/1.73 m2/year). ΔGFR is usually assumed to be constant, but the hyperfiltration theory suggests that it accelerates in severe uraemia. A retrospective analysis of estimated GFR (eGFR) calculated from the Modification of Diet in Renal Disease equation was performed to evaluate whether ΔGFR is constant or accelerating. Methods: 1,441 patients attending a nephrology clinic over a 21-year period, with an initial eGFR <60 ml/min/1.73 m2 and an observation period ≧2 years, were included. eGFR was calculated from all creatinine measurements. 420 patients developed end-stage renal disease (ESRD). First- and second-order polynomial regression analysis of eGFR against time was performed for each patient individually. Patients had accelerating uraemia progression if the second-order term coefficient was negative. Results: The initial eGFR was 30.8 ±15.1 ml/min/1.73 m2. The second-order coefficient was median –0.15 ml/min/1.73 m2/year2 (interquartile range –0.92, +0.34). Significantly more patients had an accelerating loss (62%, p < 0.001). Acceleration was mainly seen when eGFR was <30 ml/min. ΔGFR was mean 1.47 ± 4.5 ml/min/1.73 m2/year (male 1.67, female 1.22). ESRD patients lost 5.4 ± 5.4 ml/min/year/1.73 m2 during the last year before ESRD. Accelerating loss was seen for all diagnoses except polycystic disease. Diagnoses with higher ΔGFR were polycystic renal disease (3.3 ml/min/1.73 m2/year), hypertensive nephropathy (2.1 ml/min/1.73 m2/year) and diabetic nephropathy (2.6 ml/min/ 1.73 m2/year). There was no evidence of improvement in overall uraemia progression during the period of observation. Conclusions: Uraemia progression in CKD stages 3–5 is not linear, but shows an accelerating trend. This suggests that hyperfiltration mechanisms play a role in CKD progression. ESRD cannot thus be predicted from previous ΔGFR alone.
The Contemporary Practice of Psychiatric Surgery: Results from a Survey of North American Functional Neurosurgeons
Authors: Lipsman Nir , Mendelsohn Daniel , Taira Takaomi , Bernstein Mark
Published: February 2011

Background: Deep brain stimulation (DBS) for psychiatric indications is becoming increasingly safe and effective. As a result, the treatment of these conditions by neurosurgeons is becoming more widespread and a larger part of the functional neurosurgeons’ practice. Given the troubled history of the field and its current renaissance, it is important to evaluate current practices, to serve as a baseline for future comparison, and to gauge changing cultural attitudes towards invasive neuromodulation. Objectives: The purpose of this study was to obtain a snapshot of the practice of the contemporary functional neurosurgeon engaged in psychiatric surgery. Current practices as well as attitudes towards the direction of the field and its future were also investigated. Methods: We designed an online survey and distributed it electronically to 299 functional neurosurgeons in North America identified by membership in the World Society for Stereotactic and Functional Neurosugery. Subsequent statistical and thematic analysis was performed on the data obtained. Results: Of 299 surveys sent out, 84 were completed (28%). Fifty percent of functional neurosurgeons are currently engaged in some form of psychiatric surgery, with DBS for obsessive-compulsive disorder and depression accounting for most cases. Most surgeons see psychiatric surgery as a growing field, with multidisciplinary teams and a greater engagement with psychiatry necessary for the expansion of the field. Opinions differed substantially on hypothetical scenarios dealing with surgical cognitive enhancement, with some in favour of it, citing patient autonomy and choice, and others drawing a clear distinction between pathologic and non-pathologic states. Conclusions: Surgery for psychiatric indications is a growing field in the contemporary functional neurosurgeon’s practice. Most neurosurgeons see the field continuing to grow and psychiatric surgery becoming a larger part of their daily practice, with the appropriate ethical and psychiatric oversight. Future editions of this survey and their results can be used to trace the development and growth of the field as technology and cultural attitudes continue to evolve.
Hypovitaminosis D Is Associated with Systemic Inflammation and Concentric Myocardial Geometric Pattern in Hemodialysis Patients with Low iPTH Levels
Authors: Bucharles Sérgio , Barberato Silvio H. , Stinghen Andrea E. , Gruber Betina , Meister Henrique , Mehl Andrieli , Piekala Luciana , Dambiski Ana C. , Souza Admar , Olandoski Márcia , Pecoits-Filho Roberto
Published: February 2011

Background: Vitamin D [25(OH)D] deficiency is a cardiovascular risk factor in the hemodialysis (HD) population. The aim of this study was to identify hypovitaminosis D in HD patients without signs of hyperparathyroidism and to analyze its association to inflammation and echocardiographic alterations. Methods: Patients on HD with iPTH <300 pg/ml not receiving vitamin D therapy were recruited. Hypovitaminosis D was defined as 25(OH)D <30 ng/ml. High-sensitivity C-reactive protein, interleukin-6 and serum albumin were used as inflammation markers. Echocardiograms were performed in an interdialytic mid-week day. Results: Sixty-one patients (mean age of 56 ± 15 years, 52% males, 93% Caucasians, 31% diabetic) were included, and 75% presented hypovitaminosis D. Inflammation was more prevalent among those with hypovitaminosis D, and these patients presented higher relative wall thickness (0.48 ± 0.11 vs. 0.42 ± 0.10 mm; p = 0.05) and lower left ventricular diastolic (49.8 ± 6.2 vs. 54.7 ± 5.8 mm; p = 0.013) and systolic (31.9 ± 5.7 vs. 36.8 ± 7.2 mm; p = 0.012) diameters. Conclusions: Hypovitaminosis D is associated with inflammation and concentric geometric pattern of the left ventricle, even in the absence of high iPTH levels. Vitamin D repletion (aiming to reduce cardiovascular complications) should also be considered in HD patients with normal or low iPTH levels.
Association Tests for X-Chromosomal Markers – A Comparison of Different Test Statistics
Authors: Loley Christina , Ziegler Andreas , König Inke R.
Published: February 2011

Objective: Genome-wide association studies have successfully elucidated the genetic background of complex diseases, but X chromosomal data have usually not been analyzed. A reason for this is that there is no consensus approach for the analysis taking into account the specific features of X chromosomal data. This contribution evaluates test statistics proposed for X chromosomal markers regarding type I error frequencies and power. Methods: We performed extensive simulation studies covering a wide range of different settings. Besides characteristics of the general population, we investigated sex-balanced or unbalanced sampling procedures as well as sex-specific effect sizes, allele frequencies and prevalence. Finally, we applied the test statistics to an association data set on Crohn’s disease. Results: Simulation results imply that in addition to standard quality control, sex-specific allele frequencies should be checked to control for type I errors. Furthermore, we observed distinct differences in power between test statistics which are determined by sampling design and sex specificity of effect sizes. Analysis of the Crohn’s disease data detects two previously unknown genetic regions on the X chromosome. Conclusion: Although no test is uniformly most powerful under all settings, recommendations are offered as to which test performs best under certain conditions.
Combination of the Killip and TIMI Classifications for Early Risk Stratification of Patients with Acute ST Elevation Myocardial Infarction
Authors: Rott David , Leibowitz David , Schwartz Roseline , Weiss A. Teddy , Behar Solomon , Hod Hanoch
Published: February 2011

Objective: The Killip classification and the Thrombolysis in Myocardial Infarction (TIMI) score have been proven to be useful tools for the early risk stratification of patients with acute myocardial infarction (MI). The Killip classification is simpler and less time consuming compared to the TIMI score. We sought to evaluate the added value of applying the TIMI score to patients prestratified with the Killip classification. Methods: A total of 1,773 consecutive acute MI patients were hospitalized in 25 coronary care units operating in Israel, and were followed up to 1 year. Results: Higher Killip class was associated with increased 1-year mortality: 6, 24, 42 and 60% in Killip 1–4, respectively. Applying the TIMI score to Killip 1 patients resulted in further stratifying the patients to low-, medium- and high-risk patient groups with 1, 8 and 19% 1-year mortality rates. Conclusions: The Killip classification is a useful tool for early risk stratification of acute MI patients. Applying the TIMI score to patients classified as Killip 1 further stratified them into low-, medium- and high-risk subgroups significantly improving stratification by the Killip classification alone.
Arterial Thromboembolic Events in Patients with Exudative Age-Related Macular Degeneration Treated with Intravitreal Bevacizumab or Ranibizumab
Authors: Carneiro Ângela M. , Barthelmes Daniel , Falcão Manuel S. , Mendonça Luis S. , Fonseca Sofia L. , Gonçalves Rita M. , Faria-Correia Fernando , Falcão-Reis Fernando M.
Published: February 2011

Background/Aims: To compare retrospectively the incidence of arterial thromboembolic events (ATEs) in patients treated with bevacizumab or ranibizumab for exudative age-related macular degeneration. Methods: Charts of 378 patients treated with at least 1 intravitreal injection of ranibizumab or bevacizumab were reviewed to calculate the incidence of ATEs. Only patients under monotherapy were analyzed. Results: ATEs occurred in 15 patients: 12 (12/97) with bevacizumab (12.4%) and 3 (3/219) with ranibizumab (1.4%) – odds ratio 10.16; 95% confidence interval 2.80–36.93; p < 0.0001. ATEs in the bevacizumab and ranibizumab cohorts included stroke, myocardial infarction, angina pectoris, peripheral thromboembolic disease, transient ischemic attack, sudden death and lethal stroke. Conclusion: In this series, bevacizumab raised the risk of ATEs when compared to ranibizumab. In an elderly population with multiple cardiovascular risk factors, the new ATEs may not be attributed exclusively to the intravitreal bevacizumab administration. These findings raise an issue that must be confirmed in randomized clinical trials.
A Nanofibrillar Surface Promotes Superior Growth Characteristics in Cultured Human Retinal Pigment Epithelium
Authors: Thieltges Fabian , Stanzel Boris V. , Liu Zengping , Holz Frank G.
Published: February 2011

Background: To evaluate the influence of surface topography on the proliferation of the retinal pigment epithelium (RPE) by comparing nanofibrillar and smooth substrates. Methods: Electrospun polyamide nanofibers (EPN) are an engineered surface mimicking native basement membranes. Commonly used plastic (polystyrene, PS) and glass substrates have a smooth topography. All were analyzed by scanning electron microscopy. RPE cultures were established from fetal and adult donors. Growth curves were established on the above substrates. Cell cycle and growth fractions were analyzed with 5-ethynyl-2′-deoxyuridine (EdU) and 4′,6-diamidino-2-phenylindole (DAPI). Results: At a magnification of ×5,000, EPN showed randomly overlapping fibers and pores. The surface of glass was slightly studded yet regular, in contrast to ideally smooth PS. Polygonal cells grew on nanofibers in a colony-like distribution, while randomly spread spindle-shaped cell morphologies were seen on smooth surfaces. This was observed at all donor ages. Initial proliferation rates were higher on EPN, and similar final cell densities were reached in all age groups, compared to an age-related decline on PS. EdU/DAPI revealed faster cell cycles on EPN. Growth fractions were higher and maintained longer on EPN. Observed substrate differences in growth behavior were statistically significant. Conclusion: Surface topography appears to induce distinct RPE proliferation characteristics.
Detection of Spinal Muscular Atrophy Carriers in a Sample of the Brazilian Population
Authors: Bueno K.C. , Gouvea S.P. , Genari A.B. , Funayama C.A. , Zanette D.L. , Silva, Jr. W.A. , Oliveira A.B. , Scola R.H. , Werneck L.C. , Marques, Jr. W.
Published: February 2011

Background: Spinal muscular atrophy is a common autosomal recessive neuromuscular disorder caused by mutations in the SMN1 gene. Identification of spinal muscular atrophy carriers has important implications for individuals with a family history of the disorder and for genetic counseling. The aim of this study was to determine the frequency of carriers in a sample of the nonconsanguineous Brazilian population by denaturing high-performance liquid chromatography (DHPLC). Methods: To validate the method, we initially determined the relative quantification of DHPLC in 28 affected patients (DHPLC values: 0.00) and 65 parents (DHPLC values: 0.49–0.69). Following quantification, we studied 150 unrelated nonconsanguineous healthy individuals from the general population. Results: Four of the 150 healthy individuals tested (with no family history of a neuromuscular disorder) presented a DHPLC value in the range of heterozygous carriers (0.6–0.68). Conclusions: Based on these results, we estimated there is a carrier frequency of 2.7% in the nonconsanguineous Brazilian population, which is very similar to other areas of the world where consanguineous marriage is not common. This should be considered in the process of genetic counseling and risk calculations.
CT Perfusion ASPECTS in the Evaluation of Acute Ischemic Stroke: Thrombolytic Therapy Perspective
Authors: Sillanpaa Niko , Saarinen Jukka T. , Rusanen Harri , Hakomaki Jari , Lahteela Arto , Numminen Heikki , Elovaara Irina , Dastidar Prasun , Soimakallio Seppo
Published: February 2011

Background and Purpose: Advances in the management of acute ischemic stroke and medical imaging are creating pressure to replace the rigid one-third middle cerebral artery (MCA) and non-contrast-enhanced CT (NCCT) Alberta Stroke Program Early CT Score (ASPECTS) thresholds used for the selection of patients eligible for intravenous thrombolytic therapy. The identification of potentially salvageable ischemic brain tissue lies at the core of this issue. In this study, the role of CT perfusion ASPECTS in the detection of reversible ischemia was analyzed. Materials and Methods: We retrospectively reviewed the clinical and imaging data of 92 consecutive patients who received intravenous thrombolytic therapy for acute (duration <3 h) ischemic stroke. Most of the patients underwent admission multimodal CT, and all patients had follow-up NCCT at 24 h. ASPECTS was assigned to all modalities and correlated with clinical and imaging parameters. Receiver-operating characteristic curve analysis was performed to determine optimal thresholds for different parameters to predict clinical outcome. Results: A perfusion defect could be detected in 50% of the patients. ASPECTS correlated inversely with the clinical outcome in the following order: follow-up NCCT > cerebral blood volume (CBV) > mean transit time (MTT) > admission NCCT. The follow-up NCCT and the CBV displayed a statistically significant difference from the admission NCCT, while the MTT did not reach statistical significance. The threshold that best differentiated between good and bad clinical outcome on admission was CBV ASPECTS ≧7. In patients with CT perfusion ASPECTS mismatch, MTT and CBV ASPECTS essentially provided the lower and upper limits for the follow-up NCCT ASPECTS, thus defining the spectrum of possible outcomes. Furthermore, CT perfusion ASPECTS mismatch strongly correlated (r = 0.83) with the mismatch between the tissue at risk and the final infarct, i.e. the amount of salvaged tissue. This finding suggests that the CT perfusion ASPECTS mismatch adequately identifies the amount of potentially salvageable ischemic brain tissue. Conclusions: Parameters derived from the use of CT perfusion ASPECTS can detect reversible ischemia and are correlated with clinical outcome.
Dementia Risk Score Predicts Cognitive Impairment after a Period of 15 Years in a Nondemented Population
Authors: Reijmer Yael D. , van den Berg Esther , van Sonsbeek Sanne , Dekker Jaqueline M. , Nijpels Giel , Stehouwer Coen D.A. , Kappelle Jaap L. , Biessels G.J.
Published: February 2011

Background/Aim: Cardiovascular risk factors play an important role in the development of cognitive impairment and dementia. We examined whether a previously designed dementia risk score based on midlife vascular risk profiles also predicts cognitive impairment 15 years later. Methods: 322 individuals without dementia from the population-based Hoorn study (aged 50–64 years) underwent a medical examination at baseline and a detailed cognitive assessment 15 years later. The relation between the risk score and late-life cognitive impairment in each of 6 domains was analyzed with logistic regression analysis. Results: The risk score was significantly related to impairment on the domains information-processing speed (p = 0.04), visuoconstruction (p = 0.04) and abstract reasoning (p = 0.02). Participants with a risk score of 9 points or more had a markedly increased risk of late-life impairment in the domains information-processing speed (OR 3.07, 95% CI 1.37–6.90; p = 0.007) and abstract reasoning (OR 3.97, 95% CI 1.07–14.71; p = 0.04). Conclusion: A previously designed risk score for dementia also predicts late-life cognitive impairment. Because such impairment can lead to complaints and functional consequences, also in individuals who do not progress to dementia, identification of individuals at risk is important and can help to target preventive strategies.
Cyclophilin A Promotes Cardiac Hypertrophy in Apolipoprotein E–Deficient Mice
Authors: Satoh Kimio , Nigro Patrizia , Zeidan Asad , Soe Nwe Nwe , Jaffré Fabrice , Oikawa Masayoshi , O'Dell Michael R. , Cui Zhaoqiang , Menon Prashanthi , Lu Yan , Mohan Amy , Yan Chen , Blaxall Burns C. , Berk Bradford C.
Published: February 2011

Objective—

Cyclophilin A (CyPA, encoded by
Ppia
) is a proinflammatory protein secreted in response to oxidative stress in mice and humans. We recently demonstrated that CyPA increased angiotensin II (Ang II)–induced reactive oxygen species (ROS) production in the aortas of apolipoprotein E (
Apoe
)
−/−
mice. In this study, we sought to evaluate the role of CyPA in Ang II–induced cardiac hypertrophy.

Methods and Results—

Cardiac hypertrophy was not significantly different between
Ppia
+/+
and
Ppia
−/−
mice infused with Ang II (1000 ng/min per kg for 4 weeks). Therefore, we investigated the effect of CyPA under conditions of high ROS and inflammation using the
Apoe
−/−
mice. In contrast to
Apoe
−/−
mice,
Apoe
−/−
Ppia
−/−
mice exhibited significantly less Ang II–induced cardiac hypertrophy. Bone marrow cell transplantation showed that CyPA in cells intrinsic to the heart plays an important role in the cardiac hypertrophic response. Ang II–induced ROS production, cardiac fibroblast proliferation, and cardiac fibroblast migration were markedly decreased in
Apoe
−/−
Ppia
−/−
cardiac fibroblasts. Furthermore, CyPA directly induced the hypertrophy of cultured neonatal cardiac myocytes.

Conclusion—

CyPA is required for Ang II–mediated cardiac hypertrophy by directly potentiating ROS production, stimulating the proliferation and migration of cardiac fibroblasts, and promoting cardiac myocyte hypertrophy.
Lipid-Free Apolipoprotein A-I and Discoidal Reconstituted High-Density Lipoproteins Differentially Inhibit Glucose-Induced Oxidative Stress in Human Macrophages
Authors: Tabet Fatiha , Lambert Gilles , Cuesta Torres Luisa F. , Hou Liming , Sotirchos Irene , Touyz Rhian M. , Jenkins Alicia J. , Barter Philip J. , Rye Kerry-Anne
Published: February 2011

Objective—

The goal of this study was to investigate the mechanisms by which apolipoprotein (apo) A-I, in the lipid-free form or as a constituent of discoidal reconstituted high-density lipoproteins ([A-I]rHDL), inhibits high-glucose–induced redox signaling in human monocyte-derived macrophages (HMDM).

Methods and Results—

HMDM were incubated under normal (5.8 mmol/L) or high-glucose (25 mmol/L) conditions with native high-density lipoproteins (HDL) lipid-free apoA-I from normal subjects and from subjects with type 2 diabetes (T2D) or (A-I)rHDL. Superoxide (O
2
−
) production was measured using dihydroethidium fluorescence. NADPH oxidase activity was assessed using lucigenin-derived chemiluminescence and a cyotochrome
c
assay. p47phox translocation to the plasma membrane, Nox2, superoxide dismutase 1 (SOD1), and SOD2 mRNA and protein levels were determined by real-time polymerase chain reaction and Western blotting. Native HDL induced a time-dependent inhibition of O
2
−
generation in HMDM incubated with 25 mmol/L glucose. Lipid-free apoA-I and (A-I)rHDL increased SOD1 and SOD2 levels and attenuated 25 mmol/L glucose-mediated increases in cellular O
2
−
, NADPH oxidase activity, p47 translocation, and Nox2 expression. Lipid-free apoA-I mediated its effects on Nox2, SOD1, and SOD2 via ABCA1. (A-I)rHDL-mediated effects were via ABCG1 and scavenger receptor BI. Lipid-free apoA-I from subjects with T2D inhibited reactive oxygen species generation less efficiently than normal apoA-I.

Conclusion—

Native HDL, lipid-free apoA-I and (A-I)rHDL inhibit high-glucose–induced redox signaling in HMDM. The antioxidant properties of apoA-I are attenuated in T2D.
C/EBP Homologous Protein Deficiency Attenuates Myocardial Reperfusion Injury by Inhibiting Myocardial Apoptosis and Inflammation
Authors: Miyazaki Yuji , Kaikita Koichi , Endo Motoyoshi , Horio Eiji , Miura Mitsutoshi , Tsujita Kenichi , Hokimoto Seiji , Yamamuro Megumi , Iwawaki Takao , Gotoh Tomomi , Ogawa Hisao , Oike Yuichi
Published: February 2011

Objective—

To investigate whether and how the endoplasmic reticulum (ER) stress–induced, CCAAT/enhancer-binding protein-homologous protein (CHOP)-mediated pathway regulates myocardial ischemia/reperfusion injury.

Methods and Results—

Wild-type and
chop
-deficient mice underwent 50 minutes of left coronary artery occlusion followed by reperfusion. Expression of
chop
and spliced
x-box binding protein-
1 (
sxbp1
) mRNA was rapidly and significantly increased in reperfused myocardium of wild-type mice.
chop
-deficient mice exhibited markedly reduced injury size after reperfusion compared with wild-type mice, accompanied by a decreasing number of terminal deoxynucleotidyl transferase dUTP nick-end labeling–positive cardiomyocytes. Interestingly, myocardial inflammation, as assessed by expression of inflammatory cytokines and chemokines and numbers of infiltrated inflammatory cells, was also attenuated in
chop
-deficient mice. Moreover, expression of
interleukin-6
mRNA in response to lipopolysaccharide was enhanced by simultaneous stimulation with thapsigargin, a potent ER stressor, in wild-type cardiomyocytes but not in
chop
-deficient cardiomyocytes. Finally, we found that superoxide was produced in reperfused myocardium and that intravenous administration of edaravone, a free radical scavenger, immediately before reperfusion significantly suppressed the superoxide overproduction and subsequent expression of
sxbp1
and
chop
mRNA, followed by reduced injury size in wild-type mice.

Conclusion—

The ER stress–induced, CHOP-mediated pathway, which is activated in part by superoxide overproduction after reperfusion, exacerbates myocardial ischemia/reperfusion injury by inducing cardiomyocyte apoptosis and myocardial inflammation.
Proteomics
Authors: Prokopi Marianna , Mayr Manuel
Published: February 2011

The concept of using stem cells for cardiovascular repair holds great potential, but uncertainties in preclinical experiments must be addressed before their therapeutic application. Contemporary proteomic techniques can help to characterize cell preparations more thoroughly and identify some of the potential causes that may lead to a high failure rate in clinical trials. The first part of this review discusses the broader application of proteomics to stem cell research by providing an overview of the main proteomic technologies and how they might help the translation of stem cell therapy. The second part focuses on the controversy about endothelial progenitor cells (EPCs) and raises cautionary flags for marker assignment and assessment of cell purity. A proteomics-led approach in early outgrowth EPCs has already raised the awareness that markers used to define their endothelial potential may arise from an uptake of platelet proteins. A platelet microparticle–related transfer of endothelial characteristics to mononuclear cells can result in a misinterpretation of the assay. The necessity to perform counterstaining for platelet markers in this setting is not fully appreciated. Similarly, the presence of platelets and platelet microparticles is not taken into consideration when functional improvements are directly attributed to EPCs, whereas saline solutions or plain medium serve as controls. Thus, proteomics shed new light on the caveats of a common stem cell assay in cardiovascular research, which might explain some of the inconsistencies in the field.
Glucocorticoid Insensitivity at the Hypoxic Blood–Brain Barrier Can Be Reversed by Inhibition of the Proteasome
Authors: Kleinschnitz Christoph , Blecharz Kinga , Kahles Timo , Schwarz Tobias , Kraft Peter , Göbel Kerstin , Meuth Sven G. , Burek Malgorzata , Thum Thomas , Stoll Guido , Förster Carola
Published: February 2011

Background and Purpose—

Glucocorticoids potently stabilize the blood–brain barrier and ameliorate tissue edema in certain neoplastic and inflammatory disorders of the central nervous system, but they are largely ineffective in patients with acute ischemic stroke. The reasons for this discrepancy are unresolved.

Methods—

To address the molecular basis for the paradox unresponsiveness of the blood–brain barrier during hypoxia, we used murine brain microvascular endothelial cells exposed to O
2
/glucose deprivation as an in vitro model. In an in vivo approach, mice were subjected to transient middle cerebral artery occlusion to induce brain infarctions. Blood–brain barrier damage and edema formation were chosen as surrogate markers of glucocorticoid sensitivity in the presence or absence of proteasome inhibitors.

Results—

O
2
/glucose deprivation reduced the expression of tight junction proteins and transendothelial resistance in murine brain microvascular endothelial cells in vitro. Dexamethasone treatment failed to reverse these effects during hypoxia. Proteasome-dependent degradation of the glucocorticoid receptor impaired glucocorticoid receptor transactivation thereby preventing physiological glucocorticoid activity. Inhibition of the proteasome, however, fully restored the blood–brain barrier stabilizing properties of glucocorticoid during O
2
/glucose deprivation. Importantly, mice treated with the proteasome inhibitor Bortezomib in combination with steroids several hours after stroke developed significantly less brain edema and functional deficits, whereas respective monotherapies were ineffective.

Conclusions—

We for the first time show that inhibition of the proteasome can overcome glucocorticoid resistance at the hypoxic blood–brain barrier. Hence, combined treatment strategies may help to combat stroke-induced brain edema formation in the future and prevent secondary clinical deterioration.
The Prognostic Effects of Poststroke Cognitive Impairment No Dementia and Domain-Specific Cognitive Impairments in Nondisabled Ischemic Stroke Patients
Authors: Narasimhalu Kaavya , Ang Sandy , De Silva Deidre Anne , Wong Meng-Cheong , Chang Hui-Meng , Chia Kee-Seng , Auchus Alexander P. , Chen Christopher P.
Published: February 2011

Background and Purpose—

There is some evidence that poststroke dementia, cognitive impairment no dementia (CIND), and mild cognitive impairment predict for poor outcomes such as dementia, death, and institutionalization. However, few studies have examined the prognostic value of CIND, CIND severity, and domain impairments in a poststroke cohort.

Methods—

A cohort of ischemic stroke patients with baseline cognitive assessments 3 months poststroke were followed up annually for outcomes of dependency, vascular events, and death for up to 5 years. Univariate and multivariate Cox proportional regression was performed to determine the ability CIND, CIND severity, and domain impairments to predict dependency, vascular outcomes, and death.

Results—

Four-hundred nineteen patients without dementia (mean age 60±11 years, 32% female) were followed for a mean of 3.2 years. Older age, diabetes, more severe strokes, CIND-mild, and CIND-moderate were independently predictive of dependency. There were no independent predictors of recurrent vascular events. Older age, diabetes, and CIND-moderate were independently predictive of death. In analyses of individual cognitive domains, impairments in visuomotor speed were independently predictive of dependency.

Conclusions—

In poststroke patients, CIND predicts dependency and death, while CIND severity discriminates patients with poor survival. Impairments in visuomotor speed independently predict dependency.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique Identifier: NCT00161070.
Sulfonylurea Use Before Stroke Does Not Influence Outcome
Authors: Favilla Christopher G. , Mullen Michael T. , Ali Myzoon , Higgins Peter , Kasner Scott E.
Published: February 2011

Background and Purpose—

Sulfonylureas block nonselective cation channels and lower serum glucose and are neuroprotective in animal models of ischemic stroke. Human data on sulfonylureas in acute stroke are sparse and conflicting. We aimed to measure the potential neuroprotective effect of prestroke sulfonylurea use in diabetic patients.

Methods—

We analyzed data from a prospective cohort of individuals with diabetes mellitus (DM) enrolled in nonreperfusion ischemic stroke trials within Virtual International Stroke Trials Archive (VISTA) comprising 1050 patients, 298 with sulfonylurea use before stroke onset. The primary outcome measures were baseline National Institutes of Health Stroke Scale score and 90-day modified Rankin Scale score.

Results—

Compared with patients on no DM medications, those with sulfonylurea use before stroke onset presented with less severe stroke (OR, 0.69; 95% CI, 0.53 to 0.89) but had similar modified Rankin Scale scores at 90 days (OR, 0.95; 95% CI, 0.74 to 1.23). Compared with those on other DM agents, there was no difference in initial stroke severity (OR, 1.04; 95% CI, 0.73 to 1.48) nor modified Rankin Scale score at 90 days (OR, 1.00; 95% CI, 0.71 to 1.40). Compared with those using any DM medication, patients not on any treatment experienced higher initial National Institutes of Health Stroke Scale scores (OR, 1.48; 95% CI, 1.18 to 1.86) and were marginally more likely to have poor outcomes (modified Rankin Scale score >2) at 90 days (OR, 1.31; 95% CI, 0.97 to 1.77).

Conclusions—

Sulfonylurea use before stroke onset did not affect stroke severity or long-term functional outcome compared with other DM treatments. This finding casts doubt on the use of sulfonylureas for prophylactic neuroprotection. Furthermore, patients not using any medication for DM appear to have more severe strokes and worse outcomes.
Primary Motor Cortex in Stroke
Authors: Cirstea Carmen M. , Brooks William M. , Craciunas Sorin C. , Popescu Elena A. , Choi In-Young , Lee Phil , Bani-Ahmed Ali , Yeh Hung-Wen , Savage Cary R. , Cohen Leonardo G. , Nudo Randolph J.
Published: February 2011

Background and Purpose—

Our goal was to investigate whether certain metabolites, specific to neurons, glial cells, or the neuronal–glial neurotransmission system, in primary motor cortices (M1), are altered and correlated with clinical motor severity in chronic stroke.

Methods—

Fourteen survivors of a single ischemic stroke located outside the M1 and 14 age-matched healthy control subjects were included. At >6 months after stroke, N-acetylaspartate,
myo
-inositol, and glutamate/glutamine were measured using proton magnetic resonance spectroscopic imaging (in-plane resolution=5×5 mm
2
) in radiologically normal-appearing gray matter of the hand representation area, identified by functional MRI, in each M1. Metabolite concentrations and analyses of metabolite correlations within M1 were determined. Relationships between metabolite concentrations and arm motor impairment were also evaluated.

Results—

The stroke survivors showed lower N-acetylaspartate and higher
myo
-inositol across ipsilesional and contralesional M1 compared with control subjects. Significant correlations between N-acetylaspartate and glutamate/glutamine were found in either M1. Ipsilesional N-acetylaspartate and glutamate/glutamine were positively correlated with arm motor impairment and contralesional N-acetylaspartate with time after stroke.

Conclusions—

Our preliminary data demonstrated significant alterations of neuronal–glial interactions in spared M1 with the ipsilesional alterations related to stroke severity and contralesional alterations to stroke duration. Thus, MR spectroscopy might be a sensitive method to quantify relevant metabolite changes after stroke and consequently increase our knowledge of the factors leading from these changes in spared motor cortex to motor impairment after stroke.
Excess Mortality and Cardiovascular Events in Patients Surviving Subarachnoid Hemorrhage
Authors: Nieuwkamp Dennis J. , Algra Ale , Blomqvist Paul , Adami Johanna , Buskens Erik , Koffijberg Hendrik , Rinkel Gabriël J.E.
Published: February 2011

Background and Purpose—

Survivors of aneurysmal subarachnoid hemorrhage (SAH) may have an increased risk of cardiovascular events because of shared risk factors. We compared incidences of vascular diseases, vascular death, and all-cause death after SAH with those in the general population.

Methods—

From the Swedish Hospital Discharge and Cause of Death registries, we identified patients with SAH between January 1987 and January 2003. Conditional on survival of 3 months after SAH, we calculated standardized mortality and incidence ratios with corresponding 95% CIs for vascular death, all-cause death, and fatal or nonfatal vascular diseases. Cumulative risks were estimated with survival analysis.

Results—

Of 17 705 patients with SAH (mean age, 59.7 years; 59.5% women), 11 374 survived at least 3 months after SAH. During follow-up (mean, 6.8 years), 2152 (18.9%) died. The risk of death was 12.9% within 5 years, 23.6% within 10 years, and 35.4% within 15 years after SAH. The overall standardized mortality ratio was 1.57 (95% CI, 1.44 to 1.70) for vascular death and 1.61 (95% CI, 1.52 to 1.70) for all-cause death. The standardized mortality ratios were particularly high in younger individuals, ranging from 2.1 to 3.7 for vascular death and from 2.1 to 2.6 for all-cause death for patients between 50 and 65 years of age. The standardized incidence ratio for fatal or nonfatal vascular diseases was 1.51 (95% CI, 1.45 to 1.56).

Conclusions—

Mortality and risk of vascular diseases are increased in survivors of SAH. Prevention of new vascular diseases after SAH by management of risk factors seems important.
Multimodal CT-Assisted Thrombolysis in Patients With Acute Stroke
Authors: Obach Víctor , Oleaga Laura , Urra Xabier , Macho Juan , Amaro Sergio , Capurro Sebastian , Gomez-Choco Manuel , San Román Luís , Cervera Alvaro , Blasco Jordi , Vargas Martha , Torres Ferrán , Chamorro Ángel
Published: February 2011

Background and Purpose—

The value of multimodal CT to assist thrombolysis has received little attention in stroke.

Methods—

We assessed prospectively the impact derived from the routine application of CT perfusion and CTA in patients with acute stroke treated consecutively with alteplase. The safety and efficacy of thrombolytic therapy were compared in 106 patients assisted with CT/CTA/CT perfusion (multimodal CT group) and 262 patients assisted without full multimodal brain imaging (control group) during a 5-year period (2005–2009).

Results—

Good outcome (modified Rankin scale score ≤2) at 3 months was increased in the multimodal group compared with controls (adjusted OR, 2.88; 95% CI, 1.50–5.52). Multimodal-assisted thrombolysis yielded superior benefits in patients treated beyond 3 hours (adjusted OR, 4.48; 95% CI, 1.68–11.98) than treated within 3 hours (adjusted OR, 1.31; 95% CI, 0.80–2.16; interaction test
P
=0.043). Mortality (14% and 15%) and symptomatic hemorrhage (5% and 7%) were similar in both groups.

Conclusions—

Multimodal CT use in routine clinical practice may heighten the overall efficacy of thrombolytic therapy in acute ischemic stroke. The benefits seem greater in patients treated >3 hours after stroke onset, but further randomized clinical trials are needed to confirm these findings.
Production Networks and Trade Patterns in East Asia: Regionalization or Globalization?
Authors: Athukorala Prema-chandra
Published: February 2011

This paper examines the implications of global production sharing for economic integration in East Asia with emphasis on the behavior of trade flows in the wake of the 2008 global financial crisis. Although trade in parts and components and final assembly within production networks (“network trade”) has generally grown faster than total world trade in manufacturing, the degree of dependence of East Asia on this new form of international specialization is proportionately larger than elsewhere in the world. Network trade has certainly strengthened economic interdependence among countries in the region with the People's Republic of China playing a pivotal role as the premier center of final assembly. However, contrary to popular belief, this has not lessened the dependence of the export dynamism of these countries on the global economy. This inference is basically consistent with the behavior of trade flows following the onset of the global financial crisis.
Malaysia Today: Lagging Economy and Ailing Higher Education System
Authors: Lim Teck Ghee
Published: February 2011

The Malaysian economy has lost economic dynamism since 2000. As education is inextricably linked with the generation of employment and the growth of income, we examine some of the major developments and outcomes in the country's higher education system and raise questions about its effectiveness in helping to generate economic growth. We find the general performance of the Malaysian higher education sector to be dismal, and we attribute this negative outcome to the use of the higher education sector by the Malaysian government as a major policy instrument to force socioeconomic restructuring along racial lines in the last 40 years.
The Size and Distribution of Hidden Household Income in China
Authors: Wang Xiaolu , Woo Wing Thye
Published: February 2011

Official Chinese data on urban household income are seriously flawed because of significant underreporting of income by respondents and non-participation by the high income groups in official household surveys. We collected urban household income and expenditure data in a way that increased their reliability and the coverage of the wealthy. We utilized the well-known relationship between Engel's coefficient and income level through two different approaches to deduce the true level of household income for each of the seven Chinese income categories (lowest income, low income, lower middle income, middle income, upper middle income, high income, and highest income). We found that the ratio of our estimated income to official income increased from 1.12 for the lowest income group to 3.19 for the highest income group. Total household disposable income in 2008 is RMB 14.0 trillion according to the official data but RMB 23.2 trillion according to our estimate; and 63 percent of the unreported income went to the wealthiest 10 percent of urban households. The income of the wealthiest 10 percent of Chinese households is really 65 times that of the poorest 10 percent instead of the 23 times reported in the official data. The Gini coefficient is clearly much higher than the usually reported figure of 0.47.

In one of the estimations, we had to drop the 76 wealthiest households (1.8 percent of our sample) from the analysis because there were no super-rich in the official data for us to match characteristics with. We therefore still understate the income of the highest income households. As the amount of unreported income indicates the degree of corruption, it is troubling that it grew 91 percent in 2005–08 compared to the 71 percent growth in gross national income. Serious institutional reforms must be enacted if corruption is not to derail economic development and social harmony.
Military Morality Transformed: Weapons and Soldiers on the Nineteenth-Century Battlefield
Authors: Phillips Gervase
Published: February 2011

The increased lethality of nineteenth-century “arms of precision” caused military formations to disperse in combat, transforming the ordinary soldier from a near automaton, drilled to deliver random fire under close supervision, into a moral agent who exercised a degree of choice about where, when, and how to fire his weapon. The emerging autonomy of the soldier became a central theme in contemporary tactical debates, which struggled to reconcile the desire for discipline with the individual initiative necessary on the battlefield. This tactical conundrum offers revealing insights about human aggression and mass violence. Its dark legacy was the propagation of military values into civilian society, thus paving the way for the political soldiers of the twentieth century.
Taking Modernity's Wager: Tocqueville, Social Capital, and the American Civil War
Authors: Neem Johann N.
Published: February 2011

Alexis de Tocqueville watched with horror as American society and politics changed in the two decades following the publication of Democracy in America. During the 1840s and 1850s, the factors that Tocqueville had earlier identified as sustaining the republic—its land and location, its laws, and its mores—had begun to undermine it. Recent work on civil society, the public sphere, and social capital is congruent with a Tocquevillian analysis of the causes of the Civil War. The associational networks that had once functioned as bridging social capital fractured under the stress of slavery, becoming sources of divisive regional, bonding social capital.
The Influence of Debate Viewing Context on Political Cynicism and Strategic Interpretations
Authors: Jomini Stroud Natalie , Stephens Maegan , Pye Danee
Published: February 2011

In 2008, Nielsen Media Research reported that between 50 million and 70 million people watched each of the presidential and vice presidential debates. Although the debates are some of the most-watched political moments, the influence of the context of debate viewing has received little attention. This study focuses on the reactions of younger Americans to watching the debates in different contexts. In particular, the authors consider the influence of three contexts on political cynicism and reactions to the debates: playing bingo, taking notes on an issue grid, and simply viewing a debate. After viewing a debate in these contexts, participants were asked to create a hypothetical headline about the debate and to answer questions about cynicism. Although there were no significant differences between conditions in terms of writing headlines containing a strategic or cynical interpretation of the debate, the language participants used documents a propensity to view the debates through a strategic lens. Furthermore, the results suggest that including an activity can help to reduce participants’ focus on the debate winner and that debate viewing is helpful for reducing cynicism.
Reading Comprehension Strategy Instruction and Attribution Retraining for Secondary Students With Learning and Other Mild Disabilities
Authors: Berkeley Sheri , Mastropieri Margo A. , Scruggs Thomas E.
Published: February 2011

A pre-post experimental design with 6-week delayed posttest was implemented to investigate the effects of reading comprehension strategy (RCS) instruction with and without attribution retraining (AR) on reading outcomes for seventh, eighth, and ninth graders with learning and other mild disabilities. Students were randomly assigned to one of three treatments: RCS+AR, RCS, or a Read Naturally (Ihnot, 1992) comparison condition. Results indicated that compared to the comparison group, both strategy instruction groups performed better on a summarization measure of comprehension after treatment producing large effect sizes. Both groups also performed better after a 6-week delay; however, only the RCS+AR group maintained a large effect size. In addition, RCS+AR students displayed higher attributions for reading success at post- and delayed posttesting. Implications for practice and future research are discussed.
Print communalism
Authors: Udupa Sahana
Published: February 2011

The emergence of a modern public sphere is attributed, in part, to the expansion of the print media, with newspapers playing a key role in the formation of an ‘imagined community’, usually imagined as a national unity. However, the role of the press in the non-Brahmin movement in princely Mysore shows that rather than shaping the formation of a homogenous and expandable rational public, newspapers identified themselves with and promoted the causes of particular caste groups. This article examines the social and political conditions under which this distinct form of journalism evolved. By doing so, it engages with and extends the post-colonial critique of Habermas’ idea of the ‘public sphere’ and modern notions of civil society.
‘Committed, Opportunists and Drifters’
Authors: Chitralekha
Published: February 2011

Who are the Naxalites today? What drives them to take on a life that, even given the adversity of their prior life conditions, seems very bleak? What are the real tenets of the ideology that make it possible for them to kill? Why are they prepared to die for it? This article is an attempt to bring out the standpoint of foot soldiers of the Naxalite movement. It categorises a sample of forty Naxalite armed cadre met with across Jharkhand and parts of Bihar in 2003 into three motivational profiles: Committed, Opportunists and Drifters. The Drifters make up most of the Naxalite armed cadre and reflect their changing spirit.