bluuebunny/crossref_metadata_2025 huggingface dataset:
Aerobic fitness does not influence the biventricular response to whole body passive heat stress
Authors: Nelson Michael D. , Haykowsky Mark J. , Petersen Stewart R. , DeLorey Darren S. , Stickland Michael K. , Cheng-Baron June , Thompson Richard B.
Published: August 2010

We examined biventricular function during passive heat stress in endurance trained (ET) and untrained (UT) men to evaluate whether aerobic fitness alters the volumetric response. Body temperature was elevated ∼0.8°C above baseline in 20 healthy men (10 ET, 64.4 ± 3.0 ml·kg−1·min−1; and 10 UT, 46.3 ± 6.2 ml·kg−1·min−1) by circulating warm water (50°C) throughout a tube-lined suit. Cardiac magnetic resonance imaging was used to measure biventricular volumes, function, filling velocities, volumetric flow rates, and left ventricular (LV) twist and circumferential strain at baseline (BL) and after 45 min of heat stress. In both groups, passive heat stress reduced biventricular end-diastolic (ET, −19.5 ± 24.0 ml; UT, −25.1 ± 23.8 ml) and end-systolic (ET, −15.9 ± 8.8 ml; UT, −17.6 ± 7.9 ml) volumes and left atrial volume (ET, −19.2 ± 11.6 ml; UT, −15.0 ± 12.7 ml) and significantly increased heart rate (ET, 29.3 ± 9.0 beats/min; UT, 31.7 ± 10.4 beats/min) and cardiac output (ET, 3.8 ± 2.2 l/min; UT, 3.2 ± 1.4 l/min) similarly, while biventricular stroke volume was unchanged. There were no between-group differences in any parameter. Heat stress increased ( P < 0.05), as a percentage of baseline values, biventricular ejection fraction (ET, 3.4 ± 5.3%; UT, 4.4 ± 3.7%), annular systolic tissue velocities (ET, 32.5 ± 34.9%; UT, 44.0 ± 38.1%), and peak LV twist (ET, 51.6 ± 59.7%; UT, 59.7 ± 54.2%) and untwisting rates (ET, 45.5 ± 42.3%; UT, 51.8 ± 55.0%) similarly in both groups. Early LV diastolic tissue and blood velocities, volumetric flow rates, and strain rates (diastole) were unchanged with heat stress in both groups. The present findings indicate that aerobic fitness does not influence the biventricular response to passive heat stress.
Voluntary activation failure contributes more to plantar flexor weakness than antagonist coactivation and muscle atrophy in chronic stroke survivors
Authors: Klein Cliff S. , Brooks Dina , Richardson Denyse , McIlroy William E. , Bayley Mark T.
Published: August 2010

The contributions of nervous system muscle activation and muscle atrophy to poststroke weakness have not been evaluated together in the same subject. Maximal voluntary contraction (MVC) torque, voluntary activation (twitch interpolation), and electromyographic (EMG) amplitude were determined bilaterally in the plantar flexors of seven chronic stroke survivors (40–63 yr, 24–51 mo poststroke). Volumes of the plantar flexor muscles were determined bilaterally with magnetic resonance imaging (MRI). The mean (±SD) contralesional (paretic) MVC torque was less than one-half of the ipsilesional leg: 56.7 ± 57.4 vs. 147 ± 35.7 Nm ( P = 0.006). Contralesional voluntary activation was only 48 ± 36.9%, but was near complete in the ipsilesional leg, 97 ± 1.9% ( P = 0.01). The contralesional MVC EMG amplitude (normalized to the maximum M-wave peak-to-peak amplitude) of the gastrocnemii and soleus were 36.0 ± 28.5 and 36.0 ± 31.0% of the ipsilesional leg. Tibialis anterior (TA) EMG coactivation was not different between the contralesional (23.2 ± 24.0% of TA MVC EMG) and ipsilesional side (12.3 ± 5.7%) ( P = 0.24). However, TA EMG coactivation was excessive (71%) in one subject and accounted for ∼8% of her weakness based on the estimated antagonist torque. Relative (%ipsilesional leg) plantar flexor and gastrocnemii volumes were 88 ± 6% ( P = 0.004) and 76 ± 15% ( P = 0.01), respectively. Interlimb volume differences of the soleus, deep plantar flexors, and peronei were not significant. Preferred walking speed (0.83 ± 0.33 m/s) was related to the contralesional MVC torque ( r2= 0.57, P = 0.05, N = 7), but the two subjects with the greatest weakness walked faster than three others. Our findings suggest that plantar flexor weakness in mobile chronic stroke survivors reflects mostly voluntary activation failure, with smaller contributions from antagonist activity and atrophy.
Phase I Study of the Selective Aurora A Kinase Inhibitor MLN8054 in Patients with Advanced Solid Tumors: Safety, Pharmacokinetics, and Pharmacodynamics
Authors: Macarulla Teresa , Cervantes Andres , Elez Elena , Rodríguez-Braun Edith , Baselga José , Roselló Susana , Sala Gemma , Blasco Inma , Danaee Hadi , Lee Yih , Ecsedy Jeffrey , Shinde Vaishali , Chakravarty Arijit , Bowman Douglas , Liu Hua , Eton Omar , Fingert Howard , Tabernero Josep
Published: August 2010

This phase I trial examined the safety, pharmacokinetics, and pharmacodynamics of MLN8054, an oral, selective, small-molecule inhibitor of Aurora A kinase. Patients with advanced solid tumors received increasing doses of MLN8054 in 28-day cycles until dose-limiting toxicity (DLT) was seen in ≥2 of 3-6 patients in a cohort. For the 10-mg and 20-mg cohorts, treatment was administered once daily on days 1 to 5 and 8 to 12. Patients in later cohorts (25, 35, 45, 55, 60, 70, and 80 mg/day) were treated four times daily on days 1 to 14, with the largest dose at bedtime (QID-14D) to mitigate benzodiazepine-like effects possibly associated with peak plasma concentrations. Patients (n = 43) received a median of 1 cycle (range, 1–10). DLT of somnolence was first noted in the 20-mg cohort. Two DLTs of somnolence (n = 1) and transaminitis (n = 1) were seen at QID-14D 80 mg. Grade 2 oral mucositis (n = 1), predicted to be a mechanistic effect, was observed only at QID-14D 80 mg. MLN8054 exposure levels were roughly linear with dose; terminal half-life was 30 to 40 hours. Pharmacodynamic analyses of skin and tumor mitotic indices, mitotic cell chromosome alignment, and spindle bipolarity provided evidence of Aurora A inhibition. MLN8054 dosing for 10 to 14 days in 28-day cycles was feasible. Somnolence and transaminitis were DLTs. Pharmacodynamic analyses in mitotic cells of both skin and tumor provided proof of mechanism for Aurora A kinase inhibition. A more potent, selective, second-generation Aurora A kinase inhibitor, MLN8237, is in clinical development. Mol Cancer Ther; 9(10); 2844–52. ©2010 AACR.
Induction of IL-6 and IL-8 by House Dust Mite Allergen Der p1 in Cultured Human Nasal Epithelial Cells Is Associated with PAR/PI3K/NFĸB Signaling
Authors: Shi Jianbo , Luo Qing , Chen Fenghong , Chen Dehua , Xu Geng , Li Huabin
Published: August 2010

Objective: The mechanism of action involved in how Dermatophagoides pteronyssinus (Der p) 1 initiates the nasal allergic cascade is poorly understood. Methods: We detected proinflammatory cytokine production (GM-CSF, TNF-α, IL-1β, IL-6, and IL-8) and associated signal molecules in primarily cultured nasal epithelial cells (NECs) from patients with allergic rhinitis (AR) after Der p1 stimulation, using ELISA, RT-PCR, and Western blot. We also evaluated the importance of protease-activated receptors (PAR)/phosphatidylinositol 3 kinase (PI3K)/NFĸB signaling pathways in IL-6 and IL-8 production using glucocorticoids and specific inhibitors, LY294002 and PDTC. Results: We observed significantly elevated IL-6 and IL-8 production (both gene and protein) in NECs after Der p1 stimulation, and demonstrated that the expressions of PAR2, pAkt, and pp65 were upregulated afterDer p1 stimulation, which were associated with IL-6 and IL-8 production in NECs. Conclusion: These findings demonstrate that the PAR/PI3K/NFĸB signaling pathway is involved in the induction of IL-6 and IL-8 in Der-p1-stimulated NECs from AR patients, and may have potential implications for the prevention and treatment of AR and asthma.
Ultraviolet Polarization Vision and Visually Guided Behavior in Fishes
Authors: Hawryshyn Craig W.
Published: August 2010

Teleost fishes are capable of detecting and behaviorally responding to linearly polarized light. Fish exhibit free-swimming spatial orientation to imposed and natural polarized light fields, and the fidelity of this spatial orientation depends heavily on UV and short wavelength content of the polarization field. Fish make fine-scale behavioral discriminations between stimuli that differ in e-vector orientation, independent of brightness. The detection of polarized light by photoreceptors is based on specializations of the disk membrane in the outer segment of cones that permit preferential absorption of axial and transverse polarized light. Differential polarization detectors that have overlapping spectral sensitivity in the UV short wavelength spectrum mediate polarization sensitivity. These differential detectors are based on cone photoreceptors that share spectral sensitivity in the UV short wavelength spectrum: the α-band of UV-sensitive cone mechanism as the vertical detector, and the β-band of mid- and long-wavelength sensitive cone mechanisms as the horizontal detector. Negative feedback of horizontal cells on cones govern opponent interactions between differentially sensitive polarization detectors. Polarization opponency functions to enhance e-vector contrast under conditions that vary in degree of polarization and ambient intensity. Ontogenetic changes in the cone mosaic, resulting from programmed cell death and regeneration of UV-sensitive cones, alter the retinal location of polarization sensitivity. These developmental changes greatly influence behavioral responses to polarized light.
Evolution and Ecology of Retinal Photoreception in Early Vertebrates
Authors: Collin Shaun P.
Published: August 2010

Visual ecology or the relationship between the visual system of an animal and its environment has proven to be a crucial research field for establishing general concepts of adaptation, specialization and evolution. The visual neuroscientist is indeed confronted with a plethora of different visual characteristics, each seemingly optimised for each species’ ecological niche, but often without a clear understanding of the evolutionary constraints at play. However, before we are able to fully understand the influence(s) of ecology and phylogeny on visual system design in vertebrates, it is first necessary to understand the basic bauplan of key representatives of each taxa. This review examines photoreception in hagfishes, lampreys, cartilaginous fishes and lungfishes with an eye to their ecology using a range of neurobiological methods including anatomy, microspectrophotometry and molecular genetics. These early vertebrates represent critical stages in evolution and surprisingly possess a level of visual complexity that is almost unrivalled in other vertebrates.
Increased Levels of Inflammation among Women with Enlarged Waist and Elevated Triglyceride Concentrations
Authors: Esmaillzadeh Ahmad , Azadbakht Leila
Published: August 2010

Background: We have evaluated the association between hypertriglyceridemic waist (HW) phenotype, markers of systemic inflammation and endothelial dysfunction in women. Methods and Results: Anthropometric and biochemical measurements were assessed in a cross-sectional study of 507 Iranian women aged 40–60 years. HW phenotype was defined as serum triacylglycerol (TG) concentration ≧150 mg/dl and a concurrent waist circumference ≧89 cm. Individuals with HW phenotype had higher anthropometric measures, were older and less physically active. After controlling for potential confounding variables, those with the HW phenotype had higher circulating levels of C-reactive protein (2.7 ± 2.3 vs. 1.3 ± 2.2 mg/l; p = 0.003), tumor necrosis factor-α (5.5 ± 2.1 vs. 2.9 ± 2.2 mg/l; p = 0.01), IL-6 (2.6 ± 1.5 vs. 1.1 ± 1.6 ng/l; p = 0.01) and E-selectin (62.4 ± 15.4 vs. 37.1 ± 16.9 ng/l; p = 0.001) compared with those with normal WC and normal serum TG levels. Further, adjustment for body mass index attenuated the associations, but all were still statistically significant. No significant difference was seen in circulating levels of serum amyloid A, secreted intercellular cell adhesion molecule 1 and secreted vascular cell adhesion molecule 1 comparing different phenotypes. Conclusion: This study provides evidence showing a positive association between HW phenotype and markers of systemic inflammation and endothelial dysfunction.
Treatment of Growth-Restricted Human Fetuses with Amino Acids and Glucose Supplementation through a Chronic Fetal Intravascular Perinatal Port System
Authors: Tchirikov M. , Kharkevich O. , Steetskamp J. , Beluga M. , Strohner M.
Published: August 2010

Objective: Intrauterine growth restriction (IUGR) carries an increased risk of mortality and morbidity. The accepted procedure to treat IUGR fetuses is premature delivery, which may increase neonatal mortality and morbidity and retards neonatal brain development. Material and Methods: We report here on intravascular supplementation with amino acids and glucose of an IUGR human fetus at 33 weeks of gestation with oligohydramnios and placental insufficiency using the port system (Norfolk Medical Products, Skokie, Ill., USA). The catheter was implanted into the umbilical vein (UV) by cordocentesis, and was then connected to a subcutaneously implanted port system. The treatment course included daily infusions of amino acid solution and 10% glucose into the UV. Results: Daily intravascular fetal nutrition significantly improved both fetal condition and fetal weight gain. No complications were seen. The patient was delivered by cesarean section in the 38th week of gestation. The female newborn weighed 2,130 g and was 47 cm long. Blood sampling from the UV after delivery showed no deviations of amino acids in comparison to standardized curves. In one-year follow-up the child’s development and weight gain was like that of children without IUGR in the anamnesis. Conclusion: This is the first report of the successful use of a subcutaneously implanted intravascular perinatal port system in IUGR human fetuses for long-term administration of nutriments into the UV of a fetus.
Association between Pulse Wave Velocity and Nerve Conduction Study in Diabetic Patients
Authors: Suh Bum Chun , Chung Pil-Wook , Moon Heui-Soo , Kim Yong Bum , Yoon Won Tae , Shim Dong Suk , Kim Sang Bum
Published: August 2010

Background/Aims: Brachial-ankle pulse wave velocity (baPWV) is a marker of vascular stiffness and is reported to be associated with diabetic neuropathy; however, the relationship between baPWV and nerve conduction study (NCS) has yet to be examined. Methods: Between January 2006 and December 2008, we investigated this relationship in diabetic patients. To this end, we reviewed the medical records of 100 diabetic patients for whom both baPWV and NCS had been examined. Results: The mean age of patients was 55.4 ± 10.6 years, and the mean duration of diabetes mellitus was 6.3 ± 7.3 years. A statistically significant inverse correlation between baPWV and NCS was observed, especially in the lower extremity sensory NCS [superficial peroneal sensory nerve action potential (SNAP), r = –0.466, p <0.05; sural SNAP, r = –0.384, p <0.01]. A multiple linear regression analysis also demonstrated a significant association between baPWV and some parameters of NCS (SNAP of sural nerve, and nerve conduction velocity of peroneal and sural nerves). Conclusion: These results indicate that the degree of systemic arterial stiffness is associated with peripheral nerve status in diabetic patients, but it is unclear what this signifies and further study is needed.
Increased Activation of the Supragenual Anterior Cingulate Cortex during Visual Emotional Processing in Male Subjects with High Degrees of Alexithymia: An Event-Related fMRI Study
Authors: Heinzel Alexander , Schäfer Ralf , Müller Hans-Wilhelm , Schieffer Andre , Ingenhag Ariane , Eickhoff Simon B. , Northoff Georg , Franz Matthias , Hautzel Hubertus
Published: August 2010

Background: One of the most prominent neurobiological models of alexithymia assumes an altered function of the anterior cingulate cortex (ACC) as the crucial neural correlate of alexithymia. So far functional imaging studies have yielded inconclusive results. Therefore, we tested this hypothesis in healthy alexithymics and nonalexithymics in an event-related fMRI study. Methods:Thirty high- and 30 low-alexithymic right-handed male subjects (selected by the 20-item Toronto Alexithymia Scale, TAS-20) were investigated with event-related fMRI using a picture viewing paradigm. The stimuli consisted of happy, fearful and neutral facial expressions (Ekman-Friesen) as well as positive, negative and neutral pictures from the International Affective Picture System. Results: Contrasting the high-alexithymic with the low-alexithymic group we observed increased activation of the supragenual ACC for different emotional valences as well as for different emotional stimuli. Moreover, there was a positive correlation of the ACC with the individual TAS-20 scores but no correlations with the individual Beck Depression Inventory scores. Additionally, there was no difference in activity of the amygdala. Conclusions: We demonstrated that the supragenual ACC is constantly activated more strongly in alexithymic subjects and that this activation is related to the symptoms of alexithymia and not to associated symptoms such as depression. Therefore, our findings support the hypothesis of an altered function of the ACC in alexithymia.
Does Association with Volume Status and Inflammation Account for the Increased Death Risk from High Peritoneal Protein Clearance in Peritoneal Dialysis?
Authors: Dong Jie , Xu Ying , Li Yanjun , Yang Zhikai
Published: August 2010

Objective: To determine if the association between high peritoneal protein clearance (PrC) and increased all-cause mortality is explained by inflammation and volume overload in continuous ambulatory peritoneal dialysis patients. Subjects and Methods: A total of 216 incident patients were enrolled. Demographics, biochemistry, inflammatory and volume status, peritoneal transport rate, fluid and solute removal were collected at baseline. Results: The median PrC was 57.2 ml/day. A high PrC was associated with more severe inflammation and volume overload. Using a multivariate regression model, for every 1-ml/day increase in PrC, the adjusted HR was 1.06 (1.00–1.12; p = 0.046) for all-cause death adjusted for age, diabetes, hemoglobin and D/Pcr. The predictability of PrC for all-cause death remained the same or mildly changed after additionally adjusted for inflammatory and volume overload markers with HR of 1.07 (1.00–1.14; p = 0.043) and 1.05 (0.99–1.12; p = 0.08), respectively. Conclusions: Peritoneal PrC, although correlated with volume overload and inflammation, is largely an independent predictor of mortality.
Clinical Outcomes in Elderly Patients with Metastatic Colorectal Cancer Receiving Bevacizumab and Chemotherapy: Results from the BRiTE Observational Cohort Study
Authors: Kozloff Mark F. , Berlin Jordan , Flynn Patrick J. , Kabbinavar Fairooz , Ashby Mark , Dong Wei , Sing Amy P. , Grothey Axel
Published: August 2010

Background: Elderly patients are underrepresented in clinical trials and frequently undertreated with standard therapy. The BRiTE observational cohort study assessed the safety and effectiveness of bevacizumab-based first-line therapy for metastatic colorectal cancer among a large cohort of elderly patients (896 patients ≧65 years, among 1,953 total patients). Methods: Treatment patterns, safety, progression-free survival (PFS), overall survival (OS) and survival beyond first progression (SBP) were analyzed by age cohorts. OS and SBP were further analyzed using Cox proportional hazards regression. Results: Median PFS (months) was similar across age cohorts (<65 years, 9.8; 65 to <75, 9.6; 75 to <80, 10.0; ≧80, 8.6). Median OS (months) decreased with age (<65 years, 26.0; 65 to <75, 21.1; 75 to <80, 20.3; ≧80, 16.2). SBP declined with age; however, a Cox model adjusting for baseline and postbaseline covariates that were imbalanced among age cohorts showed a reduced independent effect of age on SBP (months) (<65 years, 12.0; 65 to <75, 11.4; 75 to <80, 11.3; ≧80, 10.0) compared with unadjusted analyses. Use of bevacizumab in subsequent postprogression regimens decreased with age. Incidence of targeted adverse events did not increase with age, except for arterial thromboembolic events (ATEs), for which Eastern Cooperative Oncology Group performance status, anticoagulation and arterial disease history were stronger prognostic factors than age. Conclusions: Elderly patients receiving bevacizumab with first-line chemotherapy showed treatment benefit, although there was reduced median survival with increasing age. There was no increased toxicity among elderly patients, except for risk of ATEs.
Increased Adiposity Does Not Exacerbate Impaired Vasodilation in Rats Exposed to Eucapnic Intermittent Hypoxia
Authors: Sweazea Karen L. , Kanagy Nancy L. , Walker Benjimen R.
Published: August 2010

Background: Although there often is a clinical co-incidence of increased adiposity and obstructive sleep apnea, each factor is independently associated with elevated oxidative stress. Objective: We hypothesized that overweight rats exposed to simulated sleep apnea would develop exacerbated oxidative stress leading to impaired endothelium-dependent vasodilation. Methods: Rats were fed either a chow or high-fat diet (HFD; 60% kcal from fat) for 6 weeks. During the final 14 days of each diet, animals were exposed to either air or eucapnic intermittent hypoxia (E-IH) to simulate sleep apnea. Results: Rats exposed to either E-IH or HFD alone showed increases of 161 and 176%, respectively, in oxidative stress (measured as thiobarbituric acid-reactive substances) compared to chow + air controls. However, oxidative stress was lower following combined HFD + E-IH treatment (132% of chow + air controls) compared to each individual treatment. All three treatment groups, chow + E-IH, HFD + air and HFD + E-IH, had increased blood pressure (144.5 ± 4.4, 148.2 ± 5.6, and 136.2 ± 2.0 mm Hg, respectively, vs. chow + air: 123 ± 2.0 mm Hg) and attenuated acetylcholine (ACh)-mediated vasodilation (78.3, 72.7, and 78.2% of the chow + air response at the highest dose of ACh) compared to chow + air controls. Combined HFD and E-IH treatment did not further impair vasodilation compared to chow + E-IH alone. Vasodilatory responses were normalized by the antioxidant EUK-134 in each treatment group. Conclusions: Increased adiposity and simulated sleep apnea impair endothelium- dependent vasodilation through enhanced generation of reactive oxygen species (ROS). However, the combined treatment does not exacerbate either ROS generation or vascular dysfunction observed with HFD or E-IH alone.
Dyadic Interrelations in Lifespan Development and Aging: How Does 1 + 1 Make a Couple? – Introduction
Authors: Hoppmann Christiane , Gerstorf Denis , Luszcz Mary
Published: August 2010

Lifespan development and aging do not take place in a vacuum. It is increasingly recognized that others, who may be very familiar such as marital partners, often play a key role in shaping the developmental trajectories of their spouses. Further, this shaping seems at least partially dependent on the prolonged interactions that result in a high level of familiarity that is conducive to affecting the feelings, actions and reactions of the other member of the dyad. The studies comprising this special series on dyadic relationships tackle a number of specific mechanisms by targeting 2 domains of functioning that are central to successful aging, namely aspects of cognitive functioning and subjective well-being. The 4 papers adopt a range of methodologies, from an experimental session to short- and longer-term longitudinal observational studies. The authors of these articles offer novel insights into the theoretical underpinnings of spousal interrelations as well as how to approach such issues analytically. The closing discussion article draws out some of the underlying themes and highlights the important promises, but also the distinct challenges, of research on couples and dyads. Key avenues for future research are outlined, especially adapting principles of an epidemiological approach to understanding cognitive aging, broadly defined. These promise to extend our understanding of dyadic interrelations in lifespan development and aging.
Bone Morphogenic Protein-4 Impairs Endothelial Function Through Oxidative Stress–Dependent Cyclooxygenase-2 Upregulation
Authors: Wong Wing Tak , Tian Xiao Yu , Chen Yangchao , Leung Fung Ping , Liu Limei , Lee Hung Kay , Ng Chi Fai , Xu Aimin , Yao Xiaoqiang , Vanhoutte Paul M. , Tipoe George L. , Huang Yu
Published: August 2010

Rationale:

Bone morphogenic protein (BMP)4 can stimulate superoxide production and exert proinflammatory effects on the endothelium. The underlying mechanisms of how BMP4 mediates endothelial dysfunction and hypertension remain elusive.

Objective:

To elucidate the cellular pathways by which BMP4-induced endothelial dysfunction is mediated through oxidative stress–dependent upregulation of cyclooxygenase (COX)-2.

Methods and Results:

Impaired endothelium-dependent relaxations, exaggerated endothelium-dependent contractions, and reactive oxygen species (ROS) production were observed in BMP4-treated mouse aortae, which were prevented by the BMP4 antagonist noggin. Pharmacological inhibition with thromboxane prostanoid receptor antagonist or COX-2 but not COX-1 inhibitor prevented BMP4-induced endothelial dysfunction, which was further confirmed with the use of
COX-1
−/−
or
COX-2
−/−
mice. Noggin and knockdown of BMP receptor 1A abolished endothelium-dependent contractions and COX-2 upregulation in BMP4-treated aortae. Apocynin and tempol treatment were effective in restoring endothelium-dependent relaxations, preventing endothelium-dependent contractions and eliminating ROS overproduction and COX-2 overexpression in BMP4-treated aortae. BMP4 increased p38 mitogen-activated protein kinase (MAPK) activity through a ROS-sensitive mechanism and p38 MAPK inhibitor prevented BMP4-induced endothelial dysfunction. COX-2 inhibition blocked the effect of BMP4 without affecting BMP4-induced ROS overproduction and COX-2 upregulation. Importantly, renal arteries from hypertensive rats and humans showed higher levels of COX-2 and BMP4 accompanied by endothelial dysfunction.

Conclusions:

We show for the first time that ROS serve as a pathological link between BMP4 stimulation and the downstream COX-2 upregulation in endothelial cells, leading to endothelial dysfunction through ROS-dependent p38 MAPK activation. This BMP4/ROS/COX-2 cascade is important in the maintenance of endothelial dysfunction in hypertension.
Carotid Bruits and Cerebrovascular Disease Risk
Authors: Pickett Christopher A. , Jackson Jeffrey L. , Hemann Brian A. , Atwood J. Edwin
Published: August 2010

Background and Purpose—

Current guidelines recommend against routine auscultation of carotid arteries, believing that carotid bruits are poor predictors of either underlying carotid stenosis or stroke risk in asymptomatic patients. We investigated whether the presence of a carotid bruit is associated with increased risk for transient ischemic attack, stroke, or death by stroke (stroke death).

Methods—

We searched Medline (1966 to December 2009) and EMBASE (1974 to December 2009) with the terms “carotid” and “bruit.” Bibliographies of all retrieved articles were also searched. Articles were included if they prospectively reported the incidence of transient ischemic attack, stroke, or stroke death in asymptomatic adults. Two authors independently reviewed and extracted data.

Results—

We included 28 prospective cohort articles that followed a total of 17 913 patients for 67 708 patient-years. Among studies that directly compared patients with and without bruits, the rate ratio for transient ischemic attack was 4.00 (95% CI, 1.8 to 9.0,
P
<0.0005, n=5 studies), stroke was 2.5 (95% CI, 1.8 to 3.5,
P
<0.0005, n=6 studies), and stroke death was 2.7 (95% CI, 1.33 to 5.53,
P
=0.002, n=3 studies). Among the larger pool of studies that provided data on rates, transient ischemic attack rates were 2.6 per 100 patient-years (95% CI, 2.0 to 3.2,
P
<0.0005, n=24 studies) for those with bruits compared with 0.9 per 100 patient-years (95% CI, 0.2 to 1.6,
P
=0.02, n=5 studies) for those without carotid bruits. Stroke rates were 1.6 per 100 patient-years (95% CI, 1.3 to 1.9,
P
<0.0005, n=26 studies) for those with bruits compared with 1.3 per 100 patient-years (95% CI, 0.8 to 1.7,
P
<0.0005, n=6) without carotid bruits, and death rates were 0.32 (95% CI, 0.20 to 0.44,
P
<0.005, n=13 studies) for those with bruits compared with 0.35 (95% CI, 0.00 to 0.81,
P
=0.17, n=3 studies) for those without carotid bruits.

Conclusion—

The presence of a carotid bruit may increase the risk of cerebrovascular disease.
Cerebral Emboli Detected by Transcranial Doppler During Cardiopulmonary Bypass Are Not Correlated With Postoperative Cognitive Deficits
Authors: Rodriguez Rosendo A. , Rubens Fraser D. , Wozny Denise , Nathan Howard J.
Published: August 2010

Background and Purpose—

High-intensity transient signals (HITS) are the transcranial Doppler representation of both air and solid cerebral emboli. We studied the frequency of HITS associated with different surgical maneuvers during cardiopulmonary bypass for coronary artery bypass graft surgery and their association with postoperative cognitive dysfunction (POCD).

Methods—

We combined 356 patients undergoing coronary artery bypass graft from 2 clinical trials who had both neuropsychological testing (before, 1 week and 3 months after surgery) and transcranial Doppler during cardiopulmonary bypass. HITS were grouped into periods that included: cannulation, cardiopulmonary bypass onset, aortic crossclamp-on, aortic crossclamp-off, side clamp-on, side clamp-off, and decannulation. POCD was defined by a decreased combined Z-score of at least 2.0 or reduction in Z-scores of at least 2.0 in 20% of the individual tests.

Results—

Incidence of POCD was 47.3% and 6.3% at 1 week and 3 months after surgery. There was no association between cardiopulmonary bypass counts of HITS and POCD at 1 week (
P
=0.617) and 3 months (
P
=0.110). No differences in HITS counts were identified at any of the surgical periods between patients with and without POCD. Factors affecting HITS counts were surgical period (
P
<0.0001), blood flow velocity (
P
=0.012), cardiopulmonary bypass duration (
P
=0.040), and clinical study (
P
=0.048).

Conclusions—

Although cerebral microemboli have been implicated in the pathogenesis of POCD, in this study that included low-risk patients undergoing coronary artery bypass surgery, there was no demonstrable correlation between the counts of HITS and POCD.
Effect of Weekend Compared With Weekday Stroke Admission on Thrombolytic Use, In-Hospital Mortality, Discharge Disposition, Hospital Charges, and Length of Stay in the Nationwide Inpatient Sample Database, 2002 to 2007
Authors: Hoh Brian L. , Chi Yueh-Yun , Waters Michael F. , Mocco J , Barker Fred G.
Published: August 2010

Background and Purpose—

A stroke “weekend effect” on mortality has been demonstrated in other countries with a possible slight effect in the United States. We studied patients with stroke in the Nationwide Inpatient Sample database for a weekend effect on thrombolytic use, in-hospital mortality, discharge disposition, hospital charges, and length of stay.

Methods—

The Nationwide Inpatient Sample 2002 to 2007 was searched for all emergency room admissions for International Classification of Diseases, 9th Revision codes corresponding to ischemic stroke. Generalized estimated equations for generalized linear models were performed, adjusting for gender, age, race, season, median income level, payer, comorbidity score, hospital region, hospital location, teaching status, bed size, and hospital annual stroke case volume to compare weekend versus weekday stroke admission incidence of thrombolytic use, in-hospital mortality, discharge disposition, hospital charges, and length of stay. The same analysis was performed using the International Classification of Diseases, 9th Revision codes for ischemic stroke AND transient cerebral ischemia to check internal validity for coding irregularities that may occur in differentiating stroke from transient ischemic attack.

Results—

There were 599 087 emergency room admissions for ischemic stroke: 159 906 weekend admissions and 439 181 weekday admissions. Generalized estimated equation for generalized linear model analysis was performed and demonstrated weekend compared with weekday patients with stroke were slightly more likely to receive thrombolytics (OR=1.114; 95% CI=1.039 to 1.194;
P
=0.003); incur slightly higher total hospital charges (effect ratio=1.011; 95% CI=1.006 to 1.017;
P
<0.001); and have slightly longer lengths of stay (effect ratio=1.021; 95% CI=1.015 to 1.027;
P
<0.001). There was no difference in in-hospital mortality or discharge disposition.

Conclusions—

There is a slight stroke weekend effect on thrombolytic use, total hospital charges, and length of stay, but no difference in in-hospital mortality or discharge disposition.
Persistent Hyperglycemia >155 mg/dL in Acute Ischemic Stroke Patients: How Well Are We Correcting It?
Authors: Fuentes Blanca , Ortega-Casarrubios Maria Angeles , SanJosé Belén , Castillo José , Leira Rogelio , Serena Joaquín , Vivancos José , Dávalos Antonio , Gil-Nuñez Antonio , Egido José , Díez-Tejedor Exuperio ,   Stroke Project of the Cerebrovascular Diseases Study Group Spanish Society of Neurology
Published: August 2010

Background and Purpose—

We aimed to analyze the frequency of persistent hyperglycemia (PH), its implications for outcome, and to document the inpatient management of hyperglycemia.

Methods—

Post hoc analysis of the GLIAS (Glycemia in Acute Stroke) study, a multicenter, prospective, and observational cohort study of 476 acute ischemic stroke patients. Capillary finger-prick glucose was determined on admission and during the first 48 hours. We defined PH was defined as at least 2 values ≥155 mg/dL. Outcome (modified Rankin Scale) was evaluated at 3 months.

Results—

PH developed in 117 patients (24.7%). PH was associated with poorer outcome (modified Rankin Scale score >2: 56.2% vs 28.1%;
P
<0.01) and higher mortality (26.7% vs 5.9%;
P
<0.01) than those with glycemia <155 mg/dL. PH ≥155 mg/dL was associated with a 4-fold increase in the odds of poor outcome at 3 months (odds ratio, 4.7; 95% confidence interval, 2.2–10.2) after adjustment for age, gender, hypertension, diabetes, stroke severity, admission glycemia, and infarct volume. Only 20% of patients with hyperglycemia ≥155 mg/dL received insulin on admission, with a progressive increase in the use of insulin during the following 48 hours. However, 114 (39.1%) out of 291 patients who received corrective treatment for hyperglycemia still had levels ≥155 mg/dL.

Conclusions—

PH ≥155 mg/dL is a common observation in acute ischemic stroke patients that is associated with poorer outcome and higher mortality. Almost 40% of patients maintained levels ≥155 mg/dL despite corrective treatment.
J-Shaped Association Between Serum Glucose and Functional Outcome in Acute Ischemic Stroke
Authors: Ntaios George , Egli Marc , Faouzi Mohamed , Michel Patrik
Published: August 2010

Background and Purpose—

Hyperglycemia after stroke is associated with larger infarct volume and poorer functional outcome. In an animal stroke model, the association between serum glucose and infarct volume is described by a U-shaped curve with a nadir ≈7 mmol/L. However, a similar curve in human studies was never reported. The objective of the present study is to investigate the association between serum glucose levels and functional outcome in patients with acute ischemic stroke.

Methods—

We analyzed 1446 consecutive patients with acute ischemic stroke. Serum glucose was measured on admission at the emergency department together with multiple other metabolic, clinical, and radiological parameters. National Institutes of Health Stroke Scale (NIHSS) score was recorded at 24 hours, and Rankin score was recorded at 3 and 12 months. The association between serum glucose and favorable outcome (Rankin score ≤2) was explored in univariate and multivariate analysis. The model was further analyzed in a robust regression model based on fractional polynomial (−2–2) functions.

Results—

Serum glucose is independently correlated with functional outcome at 12 months (OR, 1.15;
P
=0.01). Other predictors of outcome include admission NIHSS score (OR, 1.18;
P
<0001), age (OR, 1.06;
P
<0.001), prestroke Rankin score (OR, 20.8;
P
=0.004), and leukoaraiosis (OR, 2.21;
P
=0.016). Using these factors in multiple logistic regression analysis, the area under the receiver-operator characteristic curve is 0.869. The association between serum glucose and Rankin score at 12 months is described by a J-shaped curve with a nadir of 5 mmol/L. Glucose values between 3.7 and 7.3 mmol/L are associated with favorable outcome. A similar curve was generated for the association of glucose and 24-hour NIHSS score, for which glucose values between 4.0 and 7.2 mmol/L are associated with a NIHSS score <7.

Discussion—

Both hypoglycemia and hyperglycemia are dangerous in acute ischemic stroke as shown by a J-shaped association between serum glucose and 24-hour and 12-month outcome. Initial serum glucose values between 3.7 and 7.3 mmol/L are associated with favorable outcome.
Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L)
Authors: Hemmen Thomas M. , Raman Rema , Guluma Kama Z. , Meyer Brett C. , Gomes Joao A. , Cruz-Flores Salvador , Wijman Christine A. , Rapp Karen S. , Grotta James C. , Lyden Patrick D.
Published: August 2010

Background and Purpose—

Induced hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke.

Methods—

Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) was a randomized, multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke. Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours. Patients presenting within 3 hours of symptom onset received standard dose intravenous alteplase and were randomized to undergo 24 hours of endovascular cooling to 33°C followed by 12 hours of controlled rewarming or normothermia treatment. Patients presenting between 3 and 6 hours were randomized twice: to receive tissue plasminogen activator or not and to receive hypothermia or not.

Results–

In total, 59 patients were enrolled. One patient was enrolled but not treated when pneumonia was discovered just before treatment. All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator. Overall, 28 patients randomized to receive hypothermia (HY) and 30 to normothermia (NT). Baseline demographics and risk factors were similar between groups. Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0; 32 (55%) were male. Cooling was achieved in all patients except 2 in whom there were technical difficulties. The median time to target temperature after catheter placement was 67 minutes (Quartile 1 57.3 to Quartile 3 99.4). At 3 months, 18% of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24% in the normothermia groups (nonsignificant). Symptomatic intracranial hemorrhage occurred in 4 patients (68); all were treated with tissue plasminogen activator <3 hours (1 received hypothermia). Six patients in the hypothermia and 5 in the normothermia groups died within 90 days (nonsignificant). Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups (
P
=0.001). The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score (
P
=0.32).

Conclusion—

This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis. Pneumonia was more frequent after hypothermia, but further studies are needed to determine its effect on patient outcome and whether it can be prevented. A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke.
Teacher Pension Incentives, Retirement Behavior, and Potential for Reform in Arkansas
Authors: Costrell Robert M. , McGee Josh B.
Published: August 2010

The authors analyze the Arkansas teacher pension plan and empirically gauge the behavioral response to incentives embedded in that plan and to possible reforms. The pattern of pension wealth accrual creates sharp incentives to work until eligible for early or normal retirement, often in one's early fifties, and to separate shortly thereafter. We estimate the effect of pension wealth accrual on teacher separation decisions using a new longitudinal data set of Arkansas teachers and find a significant impact. We then simulate the response to eliminating early retirement and raising the service requirement for normal retirement. We also simulate a shift to a constant accrual retirement plan. The response to both reforms is complex, as some would leave earlier and others stay longer. A constant accrual plan smoothes the pattern of retirement behavior as individuals tailor decisions to their own preferences instead of those built into the pension formula.
Distribution of Benefits in Teacher Retirement Systems and Their Implications for Mobility
Authors: Costrell Robert M. , Podgursky Michael
Published: August 2010

While it is generally understood that defined benefit pension systems concentrate benefits on career teachers and impose costs on mobile teachers, there has been very little analysis of the magnitude of these effects. The authors develop a measure of implicit redistribution of pension wealth among teachers at varying ages of separation. Compared with a neutral system, we find that often about half of an entering cohort's net pension wealth is redistributed to teachers who separate in their fifties from those who separate earlier, and we also identify some variation across six state systems. This implies large costs for interstate mobility. We estimate that teachers who split a thirty-year career between two pension plans often lose over half their net pension wealth compared with teachers who complete a career in a single system. Plan options that permit purchases of service years mitigate few or none of these losses. It is difficult to explain these patterns of costs and benefits on efficiency grounds. More likely explanations include the relative influence of senior versus junior educators in interest group politics and a coordination problem between states.
Khaleeji-Capital: Class-Formation and Regional Integration in the Middle-East Gulf
Authors: Hanieh Adam
Published: August 2010

The countries of the Gulf Cooperation Council (Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates) are most typically understood from the perspective of their position as the world’s key oil- and gas-producing states. This essay explores the largely-overlooked processes of class-formation in the GCC, and argues that very profound tendencies of capital-internationalisation are occurring alongside Gulf regional integration. The circuits of capital are increasingly cast at the pan-Gulf scale, and a capitalist class – described as khaleeji-capital – is emerging around the accumulation-opportunities presented within the new regional space. The formation of khaleeji-capital represents the development of a class increasingly aligned with the interests of imperialism and has important ramifications for understanding the region’s political economy.
Response to William Beik and David Parker
Authors: Heller Henry
Published: August 2010

This debate with William Beik and David Parker concerns whether a capitalist bourgeoisie developed in the ancien régime. Parker asserts that, in 1789, this class at best was new and unfledged. Beik claims that it is unhistorical to speak of its existence. Addressing their arguments, I re-iterate that the existence of a capitalist bourgeoisie was of long standing. It emerged from the sixteenth century onwards, buoyed by primitive accumulation and strengthened itself even in the face of the so-called offensive of rent under seventeenth-century absolutism.
William Morris and Edward Burne-Jones: Interlacings, Caroline Arscott, New Haven: Yale University Press, 2008./The Poetry of Chartism: Aesthetics, Politics, History, Mike Sanders, Cambridge: Cambridge University Press, 2009.
Authors: Edwards Steve
Published: August 2010

New books by Caroline Arscott and Mike Sanders return to the vexed problem of Marxism and aesthetics. For some time, there has been an intense suspicion of aesthetic thought in Marxist circles, where it is perceived as an ideology perpetrating a false resolution of contradictions. Arscott and Sanders understand aesthetics to be at the heart of the communist imagination: Arscott offers a detailed investigation of how the body is inhabited in the art of William Morris and Edward Burne-Jones; Sanders considers the figure of the poet in Chartism as a spur to radicalism. Engaging with these books, this review calls for a Marxist reconsideration of aesthetic thought and artistic practice.
Topographies of Class: Modern Architecture and Mass Society in Weimar Berlin, Sabine Hake, Ann Arbor: University of Michigan Press, 2008
Authors: Hatherley Owen
Published: August 2010

The Weimar-Republic, and the modernist architecture and planning that was born there, is still a contested place, from whence liberals, reactionaries and Marxists can all trace their lineage. Sabine Hake’s Topographies of Class attempts to clarify this contestation, through an interdisciplinary study of the modernist geography of the interwar-capital, Berlin. The book offers many new insights into the Weimar-era city, countering a tendency on the Left to reject the twentieth-century city in favour of the romanticised ‘capitals of the nineteenth century’, with their insurgent proletariat and their lushly ornamented boulevards. Topographies of Class is a reminder that, irrespective of the era’s rejection of ornament and romanticism, it was a site of class-struggle as intense as that of the Paris of the 1870s. However, Hake’s study is dominated by a conception of class as an ‘identity’, akin to the identity-politics of race or gender, leading to an argument centred on the suppression or expression of ‘class-difference’ rather than class-struggle. In the process, her reading of the city’s modernism becomes overly one-sided, as a period of tension between labour and capital is read, under the influence of Manfredo Tafuri and Italian post-Marxist architectural theory, as being governed almost solely by the logic of Fordist capital.
Heresy Hunting in the New Millennium
Authors: Burke Tony
Published: August 2010

The popularity of Dan Brown’s The Da Vinci Code has led to a surge of attacks on Christian Apocryphal literature by conservative New Testament scholars (e.g., Ben Witherington III, Craig Evans, Darrell L. Bock). The work of these scholars is transparently polemical—for example, Evans states that his book, Fabricating Jesus, was written “to defend the original witnesses to the life, death and resurrection of Jesus” (p. 17). And their methods are not new; indeed they use the same rhetorical strategies employed by such early heresiologists as Irenaeus, including the use of sarcasm and invective to describe their opponents, the intentional misrepresentation of the heretics’/scholars’ views and the content of the primary texts, the excerpting of material from the texts in order to expose their absurdities, and the demonization of their opponents by associating them with the powers of darkness. This article illustrates the parallels between modern critics and the ancient heresy hunters but focuses particularly on how the two groups use and abuse the apocryphal texts. Perhaps we can learn from the contemporary debate something about the reception of the Christian Apocrypha in antiquity.