bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise training during diabetes attenuates cardiac ryanodine receptor dysregulation
Authors: Shao Chun-Hong , Wehrens Xander H. T. , Wyatt Todd A. , Parbhu Sheeva , Rozanski George J. , Patel Kaushik P. , Bidasee Keshore R.
Published: January 2009

The present study was undertaken to assess the effects of exercise training (ExT) initiated after the onset of diabetes on cardiac ryanodine receptor expression and function. Type 1 diabetes was induced in male Sprague-Dawley rats using streptozotocin (STZ). Three weeks after STZ injection, diabetic rats were divided into two groups. One group underwent ExT for 4 wk while the other group remained sedentary. After 7 wk of sedentary diabetes, cardiac fractional shortening, rate of rise of left ventricular pressure, and myocyte contractile velocity were reduced by 14, 36, 44%, respectively. Spontaneous Ca2+spark frequency increased threefold, and evoked Ca2+release was dyssynchronous with diastolic Ca2+releases. Steady-state type 2 ryanodine receptor (RyR2) protein did not change, but its response to Ca2+was altered. RyR2 also exhibited 1.8- and 1.5-fold increases in phosphorylation at Ser2808and Ser2814. PKA activity was reduced by 75%, but CaMKII activity was increased by 50%. Four weeks of ExT initiated 3 wk after the onset of diabetes blunted decreases in cardiac fractional shortening and rate of left ventricular pressure development, increased the responsiveness of the myocardium to isoproterenol stimulation, attenuated the increase in Ca2+spark frequency, and minimized dyssynchronous and diastolic Ca2+releases. ExT also normalized the responsiveness of RyR2 to Ca2+activation, attenuated increases in RyR2 phosphorylation at Ser2808and Ser2814, and normalized CaMKII and PKA activities. These data are the first to show that ExT during diabetes normalizes RyR2 function and Ca2+release from the sarcoplasmic reticulum, providing insights into mechanisms by which ExT during diabetes improves cardiac function.
Anticipated Impact of Hand‐Hold Position on the Electromagnetic Interaction of Different Antenna Types/Positions and a Human in Cellular Communications
Authors: Al-Mously Salah I. , Abousetta Marai M.
Published: January 2009

This paper is intended to investigate intensely the impact of multipossible hand‐hold positions on the electromagnetic (EM) interaction of handset antennas and a human by using a finite‐difference time‐domain (FDTD) method. Candy‐bar handsets with different external and internal antenna positions operating in the GSM900, GSM1800/DCS, and UMTS/IMT‐2000 bands are hereby simulated with configuration of the most parts in order to achieve the commercially available handset model design. Homogeneous and heterogeneous phantoms both are used to simulate the human head, whereas, a semirealistic model with three different tissues is designed to simulate a human hand holding a set. Both of the antenna performance including the total isotropic sensitivity (TIS) and the specific absorption rate (SAR) in tissues are examined for the different suggested applicable cases, where various positions of antenna, handset and hand are considered in simulations. This simulation study determines that both of the antenna performance and the SAR in tissues significantly alter owing to the positioning of the handset against user′s head at different hand levels; where a maximum alteration is observed due to the exposure of handset with internal antenna, as compared with the handset having external antenna.
Impact of Bimodal Traffic on Latency in Optical Burst Switching Networks
Authors: Chen Yuhua , Verma Pramode K.
Published: January 2009

This paper analyzes the impact of bimodal traffic composition on latency in optical burst switching networks. In particular, it studies the performance degradation to short‐length packets caused by longer packets, both of which are part of a heterogeneous traffic model. The paper defines a customer satisfaction index for each of the classes of traffic, and a composite satisfaction index. The impact of higher overall utilization of the network as well as that of the ratio of the traffic mix on each of the customer satisfaction indices is specifically addressed.
On the q‐Extension of Apostol‐Euler Numbers and Polynomials
Authors: Kim Young-Hee , Kim Wonjoo , Jang Lee-Chae
Published: January 2009

Recently, Choi et al. (2008) have studied the q‐extensions of the
Apostol‐Bernoulli and the Apostol‐Euler polynomials of order n and multiple
Hurwitz zeta function. In this paper, we define Apostol′s type q‐Euler numbers
En,q,ξ and q‐Euler polynomials En,q,ξ(x). We obtain the generating functions
of En,q,ξ
and En,q,ξ(x), respectively. We also have the distribution relation for
Apostol′s type q‐Euler polynomials. Finally, we obtain q‐zeta function associated
with Apostol′s type q‐Euler numbers and Hurwitz_s type q‐zeta function
associated with Apostol′s type q‐Euler polynomials for negative integers.
Strong Convergence Theorem by Monotone Hybrid Algorithm for Equilibrium Problems, Hemirelatively Nonexpansive Mappings, and Maximal Monotone Operators
Authors: Cheng Yun , Tian Ming
Published: January 2009

We introduce a new hybrid iterative algorithm for finding a common element of the set of fixed points of hemirelatively nonexpansive mappings and the set of solutions of an equilibrium problem and for finding a common element of the set of zero points of maximal monotone operators and the set of solutions of an equilibrium problem in a Banach space. Using this theorem, we obtain three new results for finding a solution of an equilibrium problem, a fixed point of a hemirelatively nonexpnasive mapping, and a zero point of maximal monotone operators in a Banach space.
Mobile Findex: Facilitating Information Access in Mobile Web Search with Automatic Result Clustering
Authors: Heimonen Tomi
Published: January 2009

Designing an effective mobile search user interface is challenging, as interacting with the results is often complicated by the lack of available screen space and limited interaction methods. We present Mobile Findex, a mobile search user interface that uses automatically computed result clusters to provide the user with an overview of the result set. In addition, it utilizes a focus-plus-context result list presentation combined with an intuitive browsing method to aid the user in the evaluation of results. A user study with 16 participants was carried out to evaluate Mobile Findex. Subjective evaluations show that Mobile Findex was clearly preferred by the participants over the traditional ranked result list in terms of ease of finding relevant results, suitability to tasks, and perceived efficiency. While the use of categories resulted in a lower rate of nonrelevant result selections and better precision in some tasks, an overall significant difference in search performance was not observed.
The Characterization of High‐Fat Diet and Multiple Low‐Dose Streptozotocin Induced Type 2 Diabetes Rat Model
Authors: Zhang Ming , Lv Xiao-Yan , Li Jing , Xu Zhi-Gang , Chen Li
Published: January 2009

Aim. Based on the previously established method, we developed a better and stable animal model of type 2 diabetes mellitus by high‐fat diet combined with multiple low‐dose STZ injections. Meanwhile, this new model was used to evaluate the antidiabetic effect of berberine.Method. Wistar male rats fed with regular chow for 4 weeks received vehicle (control groups), rats fed with high‐fat diet for 4 weeks received different amounts of STZ once or twice by intraperitoneal injection (diabetic model groups), and diabetic rats were treated with berberine (100 mg/kg, berberine treatment group). Intraperitoneal glucose tolerance test and insulin tolerance test were carried out. Moreover, fasting blood glucose, fasting insulin, total cholesterol, and triglyceride were measured to evaluate the dynamic blood sugar and lipid metabolism.Result. The highest successful rate (100%) was observed in rats treated with a single injection of 45 mg/kg STZ, but the plasma insulin level of this particular group was significantly decreased, and ISI has no difference compared to control group. The successful rate of 30 mg/kg STZ twice injection group was significantly high (85%) and the rats in this group presented a typical characteristic of T2DM as insulin resistance, hyperglycemia, and blood lipid disorder. All these symptoms observed in the 30 mg/kg STZ twice injection group were recovered by the treatment of berberine.Conclusion. Together, these results indicated that high‐fat diet combined with multiple low doses of STZ (30 mg/kg at weekly intervals for 2 weeks) proved to be a better way for developing a stable animal model of type 2 diabetes, and this new model may be suitable for pharmaceutical screening.
High‐Pressure Synthesis and Study of NO+NO3− and NO2+NO3− Ionic Solids
Authors: Kuznetsov A. Yu. , Dubrovinsky L. , Kurnosov A. , Lucchese M. M. , Crichton W. , Achete C. A.
Published: January 2009

Nitrosonium‐nitrate and dinitrogen pentoxide ionic crystals were synthesized by laser heating of a condensed oxygen‐rich O2‐N2 mixture compressed to different pressures, up to 40 GPa, in a diamond anvil cell (DAC). High‐pressure/high‐temperature Raman and X‐ray diffraction studies of synthesized samples disclosed a transformation of compound to crystal at temperatures above ambient and pressures below 9 GPa. High‐pressure experiments revealed previously unreported bands in Raman spectra of and ionic crystals. Structural properties of both ionic compounds are analyzed. Obtained experimental results support a hypothesis of a rotational disorder of NO+ complexes in and indicate a rotational disorder of ionic complexes in solid.
Climate Change and Malaria in Canada: A Systems Approach
Authors: Berrang-Ford L. , MacLean J. D. , Gyorkos Theresa W. , Ford J. D. , Ogden N. H.
Published: January 2009

This article examines the potential for changes in imported and autochthonous malaria incidence in Canada as a consequence of climate change. Drawing on a systems framework, we qualitatively characterize and assess the potential direct and indirect impact of climate change on malaria in Canada within the context of other concurrent ecological and social trends. Competent malaria vectors currently exist in southern Canada, including within this range several major urban centres, and conditions here have historically supported endemic malaria transmission. Climate change will increase the occurrence of temperature conditions suitable for malaria transmission in Canada, which, combined with trends in international travel, immigration, drug resistance, and inexperience in both clinical and laboratory diagnosis, may increase malaria incidence in Canada and permit sporadic autochthonous cases. This conclusion challenges the general assumption of negligible malaria risk in Canada with climate change.
Smallpox and Season: Reanalysis of Historical Data
Authors: Nishiura Hiroshi , Kashiwagi Tomoko
Published: January 2009

Seasonal variation in smallpox transmission is one of the most pressing ecological questions and is relevant to bioterrorism preparedness. The present study reanalyzed 7 historical datasets which recorded monthly cases or deaths. In addition to time series analyses of reported data, an estimation and spectral analysis of the effective reproduction number at calendar time , , were made. Meteorological variables were extracted from a report in India from 1890–1921 and compared with smallpox mortality as well as . Annual cycles of smallpox transmission were clearly shown not only in monthly reports but also in the estimates of . Even short-term epidemic data clearly exhibited an annual peak every January. Both mortality and revealed significant negative association () and correlation (), respectively, with humidity. These findings suggest that smallpox transmission greatly varies with season and is most likely enhanced by dry weather.
Effects of Climate Change on Ticks and Tick-Borne Diseases in Europe
Authors: Gray J. S. , Dautel H. , Estrada-Peña A. , Kahl O. , Lindgren E.
Published: January 2009

Zoonotic tick-borne diseases are an increasing health burden in Europe and there is speculation that this is partly due to climate change affecting vector biology and disease transmission. Data on the vector tickIxodes ricinussuggest that an extension of its northern and altitude range has been accompanied by an increased prevalence of tick-borne encephalitis. Climate change may also be partly responsible for the change in distribution ofDermacentor reticulatus. Increased winter activity of  I. ricinusis probably due to warmer winters and a retrospective study suggests that hotter summers will change the dynamics and pattern of seasonal activity, resulting in the bulk of the tick population becoming active in the latter part of the year. Climate suitability models predict that eight important tick species are likely to establish more northern permanent populations in a climate-warming scenario. However, the complex ecology and epidemiology of such tick-borne diseases as Lyme borreliosis and tick-borne encephalitis make it difficult to implicate climate change as the main cause of their increasing prevalence. Climate change models are required that take account of the dynamic biological processes involved in vector abundance and pathogen transmission in order to predict future tick-borne disease scenarios.
Asymmetric Composite Nanoparticles with Anisotropic Surface Functionalities
Authors: Wang Yilong , Xu Hong , Qiang Weili , Gu Hongchen , Shi Donglu
Published: January 2009

Asymmetric inorganic/organic composite nanoparticles with anisotropic surface
functionalities represent a new approach for creating smart materials, requiring the selective
introduction of chemical groups to dual components of composite, respectively. Here, we
report the synthesis of snowman‐like asymmetric silica/polystyrene heterostructure with
anisotropic functionalities via a chemical method, creating nanostructure possibly offering
two‐sided biologic accessibility through the chemical groups. Carboxyl group was introduced
to polystyrene component of the snowman‐like composites by miniemulsion polymerization
of monomer on local surface of silica particles. Moreover, amino group was then grafted to
remained silica surface through facile surface modification of the composite nanoparticles.
The asymmetric shape of these composites was confirmed by TEM characterization.
Moreover, characteristics of anisotropic surface functionalities were indicated by Zeta
potential measurement and confocal laser microscopy after being labeled with fluorescent
dyes. This structure could find potential use as carriers for biological applications.
Endoscopic Management of Upper Tract Urothelial Carcinoma
Authors: Moore K. , Khastgir J. , Ghei M.
Published: January 2009

Nephroureterectomy is currently the gold standard for management of upper urinary tract urothelial carcinoma despite it results. This review article in the loss of a renal unit. The ultimate aim of endoscopic management of this condition is cancer control whilst preserving renal function and the integrity of the urinary tract. Endoscopic treatments of upper tract TCC include the antegrade percutaneous and retrograde ureteroscopic approaches. This review article summarizes the endoscopic management of upper tract urothelial carcinoma, surveillance of the disease after endoscopic management and adjuvant therapy. The main message regarding endoscopic management of upper tract urothelial cancer is that patients must be carefully selected. Patient selection is based on tumour size, grade, and multifocality. Single low-grade tumours, less than 1.5 cm in size, generally have a good outcome with endoscopic treatment provided that they have regular ureteroscopic surveillance. Ureteroscopic treatment of high-grade tumours is essentially palliative. It is essential that patients are motivated and compliant as lifetime follow-up is necessary. However, until large randomized trials with long-term follow-up are performed, endoscopic management cannot be considered a standard treatment and should be limited to poor performance status patients.
Time‐Resolved Observation of Deposition Process of Ultrananocrystalline Diamond/Hydrogenated Amorphous Carbon Composite Films in Pulsed Laser Deposition
Authors: Hanada Kenji , Nishiyama Takashi , Yoshitake Tsuyoshi , Nagayama Kunihito
Published: January 2009

Optical emission spectroscopy was used to study pulsed laser ablation of graphite in a hydrogen atmosphere wherein ultrananocrystalline diamond (UNCD)/hydrogenated amorphous carbon (a‐C:H) composite films were grown on heated substrates. Time‐resolved photographs of a plume that expanded from a laser‐irradiation spot toward a substrate were taken using a high‐speed ICCD camera equipped with narrow‐bandpass filters. While the emissions from C atoms and C2 dimers lasted above the laser‐irradiation spot on the target, the emission from C+ ions lasted above the substrate surface for approximately 7 microseconds, although the emission lifetime of species is generally approximately 10 nanoseconds. This implies that C+ ions actively collided with each other above the substrate surface for such a long time. We believe that the keys to UNCD growth in PLD are the supply of highly energetic carbon species at a high density to the substrate and existence of atomic hydrogen during the growth.
Inactivating Mutations of Luteinizing Hormone β-Subunit or Luteinizing Hormone Receptor Cause Oligo-Amenorrhea and Infertility in Women
Authors: Arnhold Ivo Jorge , Lofrano-Porto Adriana , Latronico Ana Claudia
Published: January 2009

Women harbouring inactivating mutations in luteinizing hormone (LH) beta subunit (LHB) or LH receptor (LHCGR) genes have similar clinical manifestations characterized by female external genitalia, spontaneous breast and pubic hair development at puberty, and normal or late menarche followed by oligo-amenorrhea and infertility. Oestradiol and progesterone levels are normal for the early to midfollicular phase, but do not reach ovulatory or luteal phase levels, confirming lack of ovulation. Notably, serum LH levels are low in patients with LHB mutations and high in those with LHCGR mutations, whereas follicle-stimulating hormone levels are normal or only slightly increased. Pelvic ultrasound has demonstrated a small or normal uterus and normal or enlarged ovaries with cysts. Women with LHB mutations may be treated with hCG (human chorionic gonadotropin) or LH, whereas those with mutations in LHCGR are resistant. Lhb and Lhcgr knockout female mice are close phenocopies of the respective human mutations, and confirm that early follicular development, low levels of oestrogen production and theca cell development are independent of LH action, which is necessary for ovulation. Although inactivating mutations in LHB and LHCGR are rare in comparison to other genetic and non-genetic causes of hypogonadism, they should be considered in the differential diagnosis of oligo-amenorrhea and infertility.
Expression and Activity of 11β-Hydroxysteroid Dehydrogenase Type 1 Enzyme in Subcutaneous and Visceral Adipose Tissue of Prepubertal Children
Authors: Mericq Verónica , Medina Pablo , Bouwman Carolien , Johnson M. Cecilia , Godoy Jorge , López Teresa , Iñiguez Germán
Published: January 2009

Background: Glucocorticoid excess promotes visceral obesity and cardiovascular disease. Ligand availability to the glucocorticoid receptor is controlled by isoforms of 11β-hydroxysteroid dehydrogenase (11β-HSD) which converts endogenous cortisone to active cortisol. Aim: To evaluate the expression and activity of 11β-HSD1 in subcutaneous adipose tissue (SC) and visceral adipose tissue (VAT) in prepubertal children with normal weight. Methods: Fourteen patients (11 female/3 male) with a mean age of 6.9 ± 0.9 years and a body mass index (BMI) of 17.4 ± 0.61 underwent elective open abdominal surgery. Results: Expression of 11β-HSD1 mRNA in SC and VAT was similar (0.8 ± 0.15 vs. 0.61 ± 0.12 AU). The activity of this enzyme in SC was significantly lower compared to VAT (1.42 ± 0.39 vs. 2.79 ± 0.61 ng cortisol/g tissue/24 h, p < 0.05). In addition, we observed a significant direct correlation with the expression of 11β-HSD1 in VAT adipose tissue with the patient’s BMI (r = 0.825, p = 0.002). Conclusions: This correlation together with the increased activity of this enzyme in visceral adipose tissue might contribute to decreased hepatic insulin sensitivity due to increased portal cortisol when BMI increases. These observations appear to be particularly important in children born with low birth weight who develop rapid early weight gain.
Fos Expression in the Rat Vestibular Nucleus Complex after Plugging the Three Semicircular Canals
Authors: Chen Bin , Yu Dongzhen , Chen Zhengnong , Yin Shankai
Published: January 2009

Hypothesis: Differential compensation after unilateral semicircular canal plugging (UCP) and unilateral labyrinthectomy (UL) may involve different expression patterns of fos mRNA and Fos protein in the vestibular nucleus complex. Background: The expression of Fos protein in the vestibular nuclei underwent spatiotemporal changes related to the compensation process following surgical UL and chemical UL. These changes were temporally related to the appearance and development of vestibular compensation in the rat. Methods: Spatiotemporal changes in both fos mRNA and protein levels in the rat brain after UCP were observed. The Fos expression pattern after UCP was compared to that after UL. Results: Greater fos mRNA and Fos protein expressions were detected in bilateral medial vestibular nuclei (MVNs) after UL than after UCP. The changes were relatively long-lived after UL compared to those following UCP. Conclusion: Differences in the expression pattern of fos mRNA and Fos protein in bilateral MVNs between UCP and UL may explain differences in compensation after UCP and UL.
A Normative Study of Early Prelingual Auditory Development
Authors: Zheng Yun , Soli Sigfrid D. , Wang Kai , Meng Juan , Meng Zhaoli , Xu Ke , Tao Yong
Published: January 2009

The normal trajectory of early prelingual auditory development from birth to 24 months of age was characterized in a sample of 120 normal-hearing infants and toddlers of Mandarin-Chinese-speaking parents. The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) was administered to parents as a structured interview during routine pediatric health examinations. Developmental trajectories for the overall IT-MAIS score, as well as for scores on the subscales that assess behavioral evidence of spontaneous detection of and responsiveness to sound and of spontaneous recognition and discrimination of sound, were represented by logarithmic regression functions. On average, these regression functions characterized over 80% of the age-related variance in each scale. The developmental trajectories revealed that by 16 months the average infant exhibited spontaneous detection of and responsiveness to sound at all times, while spontaneous recognition and discrimination of sound was seen at all times after 26 months. The trajectory for the overall IT-MAIS scale, which combines the two subscales, reached ceiling at 22 months. The overall trajectory for Chinese infants closely matches the trajectory for normal-hearing infants of Arabic- and Hebrew-speaking parents in Israel. The Chinese IT-MAIS also exhibits similar internal consistency and item reliability to the German, Polish, and British English IT-MAIS scales. These similarities seen across culturally and linguistically diverse populations suggest the early prelingual auditory development follows the same, or a very similar course, in all infants.
Investigation of the Effect of Various Fluoride Compounds and Preparations Thereof on Erosive Tissue Loss in Enamel in vitro
Authors: Schlueter N. , Duran A. , Klimek J. , Ganss C.
Published: January 2009

Metal fluoride preparations are promising in view of protection against dental erosion. The aim of this study was to screen the effect fluoride preparations containing various polyvalent metal cations had on erosion progression under increasingly severe erosive conditions in human enamel in vitro. Specimens were subjected to a cyclic de- and remineralisation procedure. Demineralisation (experiment E1 and E2a: 6 × 2 min/day, experiment E2b: 6 × 5 min/day) was performed with 0.05 M citric acid (pH 2.3). Fluoridation directly followed demineralisation and was reduced stepwise (E1: 6 × 2 min/day, E2a and E2b: 2 × 2 min/day). The test solutions were: ZnF2 (E1), AmF/NaF/CuSO4 (E1), TiF4/AmF/Zn lactate (E1), TiF4 (E1, E2a), TiF4/AmF (E2a), TiF4/AmF/NaF (E2a), TiF4/AmF/ZnF2 (E1, E2a, E2b), AmF/NaF/SnCl2 (2,800 mg/l Sn2+; E1, E2a, E2b), AmF/NaF/SnCl2-1 (700 mg/l Sn2+; E2a, E2b), all 1,500 ppm F–, pH 4.5, and AmF/SnF2 (positive control, pH 4.2, 250 ppm F–; E1, E2a, E2b). In the negative control group, specimens were not fluoridated. Tissue loss was determined by profilometry after the last experimental day. Under mild conditions (E1), tin- and titanium-containing solutions were of marked efficacy and could nearly completely inhibit erosive tissue loss (reduction between 94.2 and 97.5%). With increasingly severe conditions (E2a, E2b), titanium lost its efficacy. Only the highly concentrated tin preparation (2,800 mg/l Sn2+) was able to reduce erosive tissue loss by 93.1%, even under severe conditions (E2b), with less frequent application of the experimental preparations. It should be considered for approaches for a symptomatic therapy of dental erosion.
Ménière’s Disease Is a Viral Neuropathy
Authors: Gacek Richard R.
Published: January 2009

Morphological and clinical evidence supports a viral neuropathy in Ménière’s disease (MD). Quantitative examination of 11 sectioned temporal bones (TBs) from 8 patients with a history of MD revealed a significant loss of vestibular ganglion cells in both the endolymph hydropic (EH) and non-EH ears. Transmission electron microscopy of vestibular ganglion cells excised from a patient with MD revealed viral particles enclosed in transport vesicles. Antiviral treatment controlled vertigo in 73 of 86 patients with vestibular neuronitis (85%) and 32 of 35 patients with MD (91%).
Indoxyl Sulfate Inhibits Nitric Oxide Production and Cell Viability by Inducing Oxidative Stress in Vascular Endothelial Cells
Authors: Tumur Zohra , Niwa Toshimitsu
Published: January 2009

Background/Aim: Cardiovascular disease is a major cause of mortality in chronic kidney disease patients. Oxidative stress and nitric oxide (NO) deficiency play an important role in vascular endothelial cell dysfunction in chronic kidney disease. To determine if the uremic toxin indoxyl sulfate (IS) induces oxidative stress and inhibits NO production and cell viability in human umbilical vein endothelial cells (HUVEC). Methods: The production of reactive oxygen species (ROS), superoxide, NO and peroxynitrite was measured using a fluorescence microplate reader. The expression of NADPH oxidases (Nox4, Nox2) was analyzed by quantitative reverse transcription-polymerase chain reaction. Cell viability was examined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate assay. Results: IS induced ROS generation in HUVEC. An inhibitor of NADPH oxidase showed an inhibitory effect on IS-induced ROS production. However, the inhibitors of xanthine oxidase, mitochondrial electron transport and NO synthase did not show any significant effect on IS-induced ROS production. Antioxidants such as vitamin E, N-acetyl-L-cysteine and vitamin C inhibited IS-induced ROS production. IS induced the expression of Nox4 mRNA and the production of superoxide and peroxynitrite in HUVEC. IS inhibited NO production in HUVEC. IS inhibited cell viability, and antioxidants preserve the inhibitory effect of IS on cell viability. Conclusions: IS inhibits NO production and cell viability by inducing ROS through induction of Nox4 in HUVEC.
Association of Serum Total Iron-Binding Capacity and Its Changes Over Time with Nutritional and Clinical Outcomes in Hemodialysis Patients
Authors: Bross Rachelle , Zitterkoph Jennifer , Pithia Juhi , Benner Deborah , Rambod Mehdi , Kovesdy Csaba P. , Kopple Joel D. , Kalantar-Zadeh Kamyar
Published: January 2009

Serum transferrin, estimated by total iron-binding capacity (TIBC), may be a marker of protein-energy wasting (PEW) in maintenance hemodialysis (MHD) patients. We hypothesized that low TIBC or its fall over time is associated with poor clinical outcomes. In 807 MHD patients in a prospective 5-year cohort, associations of TIBC and its changes over time with outcomes were examined after adjustment for case-mix and markers of iron stores and malnutrition-inflammation including serum interleukin-6, iron and ferritin. Patients with serum TIBC ≥250 mg/dl had higher body mass index, triceps and biceps skinfolds and mid-arm muscle circumference and higher serum levels of iron but lower ferritin and inflammatory markers. Some SF-36 quality of life (QoL) components were worse in the lowest and/or highest TIBC groups. Mortality was incrementally higher in lower TIBC levels (p-trend <0.001). Adjusted death hazard ratio was 1.75 (95% CI: 1.00–3.05, p = 0.05) for TIBC <150 compared to TIBC of 200–250 mg/dl. A fall in TIBC >20 mg/dl over 6 months was associated with a death hazard ratio of 1.57 (95% CI: 1.04–2.36, p = 0.03) compared to the stable TIBC group. Hence, low baseline serum TIBC is associated with iron deficiency, PEW, inflammation, poor QoL and mortality, and its decline over time is independently associated with increased death risk.
Fibrinogen-γ C-Terminal Fragments Induce Endothelial Barrier Dysfunction and Microvascular Leak via Integrin-Mediated and RhoA-Dependent Mechanism
Authors: Guo Mingzhang , Daines Dayle , Tang Jing , Shen Qiang , Perrin Rachel M. , Takada Yoshikazu , Yuan Sarah Y. , Wu Mack H.
Published: January 2009

Objectives—

The purposes of this study were to characterize the direct effect of the C-terminal fragment of fibrinogen γ chain (γC) on microvascular endothelial permeability and to examine its molecular mechanism of action.

Methods and Results—

Intravital microscopy was performed to measure albumin extravasation in intact mesenteric microvasculature, followed by quantification of hydraulic conductivity in single perfused microvessels. Transendothelial electric resistance was measured in microvascular endothelial cells in combination with immunoblotting and immunocytochemistry. The results show that γC induced time- and concentration-dependent increases in protein transvascular flux and water permeability and decreases in endothelial barrier function, coupled with Rho GTPase activation, myosin light chain phosphorylation, and stress fiber formation. Depletion of RhoA via siRNA knockdown or pharmacological inhibition of RhoA signaling attenuated γC-induced barrier dysfunction. Imaging analyses demonstrated binding of γC to endothelial cells; the interaction was inhibited during blockage of the αvβ3 integrin. Furthermore, in vivo experiments showed that the microvascular leak response to γC was attenuated in integrin β3
−/−
animals.

Conclusion—

Fibrinogen-γ C terminus directly interacts with the microvascular endothelium causing fluid and protein leak. The endothelial response to γC involves an integrin receptor-mediated RhoA-dependent signaling pathway that leads to paracellular hyperpermeability.
Caspase-8 Is Involved in Neovascularization-Promoting Progenitor Cell Functions
Authors: Scharner Dörte , Rössig Lothar , Carmona Guillaume , Chavakis Emmanouil , Urbich Carmen , Fischer Ariane , Kang Tae-Bong , Wallach David , Chiang Yungping Jeffrey , Deribe Yonathan Lissanu , Dikic Ivan , Zeiher Andreas M. , Dimmeler Stefanie
Published: January 2009

Objective—

Endothelial progenitor cells (EPCs) comprise a heterogeneous population of cells, which improve therapeutic neovascularization after ischemia. The neovascularization-promoting potential of progenitor cells depends on survival and retention of the infused cells to the tissue. Caspases mediate apoptosis but are also involved in other critical biological processes. Therefore, we aimed to address the role of caspases in proangiogenic cells.

Methods and Results—

The caspase-8 inhibitor zIETD abrogated the ex vivo formation of EPCs, inhibited EPC adhesion and migration, and reduced their capacity to improve neovascularization in vivo. Consistently, cells isolated from caspase-8-deficient mice exhibited a reduced capacity for enhancing neovascularization when transplanted into mice after hindlimb ischemia. Because inhibition of Caspase-8 reduced the adhesion and homing functions of EPCs, we further determined the surface expression of integrins and receptors involved in cell recruitment to ischemic tissues. Pharmacological inhibition of caspase-8 and genetic depletion of caspase-8 reduced the expression of the fibronectin receptor subunits α5 and β1 and the SDF-1 receptor CXCR4. Moreover, we identified the E3 ubiquitin ligase Cbl-b, which negatively regulates integrin and receptor-mediated signaling, as a potential Caspase-8 substrate.

Conclusion—

In summary, our data demonstrate a novel apoptosis-unrelated role of caspase-8 in proangiogenic cells.
Free Cholesterol Accumulation in Macrophage Membranes Activates Toll-Like Receptors and p38 Mitogen-Activated Protein Kinase and Induces Cathepsin K
Authors: Sun Yu , Ishibashi Minako , Seimon Tracie , Lee Mingsum , Sharma Sudarshana M. , Fitzgerald Katherine A. , Samokhin Andriy O. , Wang Yibin , Sayers Scott , Aikawa Masanori , Jerome W. Gray , Ostrowski Michael C. , Bromme Dieter , Libby Peter , Tabas Ira A. , Welch Carrie L. , Tall Alan R.
Published: January 2009

The molecular events linking lipid accumulation in atherosclerotic plaques to complications such as aneurysm formation and plaque disruption are poorly understood. BALB/c-
Apoe
−/−
mice bearing a null mutation in the
Npc1
gene display prominent medial erosion and atherothrombosis, whereas their macrophages accumulate free cholesterol in late endosomes and show increased cathepsin K (
Ctsk
) expression. We now show increased cathepsin K immunostaining and increased cysteinyl proteinase activity using near infrared fluorescence imaging over proximal aortas of
Apoe
−/−
,
Npc1
−/−
mice. In mechanistic studies, cholesterol loading of macrophage plasma membranes (cyclodextrin–cholesterol) or endosomal system (AcLDL+U18666A or
Npc1
null mutation) activated Toll-like receptor (TLR) signaling, leading to sustained phosphorylation of p38 mitogen-activated protein kinase and induction of p38 targets, including
Ctsk
,
S100a8
,
Mmp8
, and
Mmp14
. Studies in macrophages from knockout mice showed major roles for TLR4, following plasma membrane cholesterol loading, and for TLR3, after late endosomal loading. TLR signaling via p38 led to phosphorylation and activation of the transcription factor
Microphthalmia
transcription factor, acting at E-box elements in the
Ctsk
promoter. These studies suggest that free cholesterol enrichment of either plasma or endosomal membranes in macrophages leads to activation of signaling via various TLRs, prolonged p38 mitogen-activated protein kinase activation, and induction of
Mmps
,
Ctsk
, and
S100a8
, potentially contributing to plaque complications.
Proinflammatory Phenotype of Perivascular Adipocytes
Authors: Chatterjee Tapan K. , Stoll Lynn L. , Denning Gerene M. , Harrelson Allan , Blomkalns Andra L. , Idelman Gila , Rothenberg Florence G. , Neltner Bonnie , Romig-Martin Sara A. , Dickson Eric W. , Rudich Steven , Weintraub Neal L.
Published: January 2009

Adipose tissue depots originate from distinct precursor cells, are functionally diverse, and modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on disease of the blood vessel wall, remain to be determined. We show that human coronary perivascular adipocytes exhibit a reduced state of adipocytic differentiation as compared with adipocytes derived from subcutaneous and visceral (perirenal) adipose depots. Secretion of antiinflammatory adiponectin is markedly reduced, whereas that of proinflammatory cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1, is markedly increased in perivascular adipocytes. These depot-specific differences in adipocyte function are demonstrable in both freshly isolated adipose tissues and in vitro–differentiated adipocytes. Murine aortic arch perivascular adipose tissues likewise express lower levels of adipocyte-associated genes as compared with subcutaneous and visceral adipose tissues. Moreover, 2 weeks of high-fat feeding caused further reductions in adipocyte-associated gene expression, while upregulating proinflammatory gene expression, in perivascular adipose tissues. These changes were observed in the absence of macrophage recruitment to the perivascular adipose depot. We conclude that perivascular adipocytes exhibit reduced differentiation and a heightened proinflammatory state, properties that are intrinsic to the adipocytes residing in this depot. Dysfunction of perivascular adipose tissue induced by fat feeding suggests that this unique adipose depot is capable of linking metabolic signals to inflammation in the blood vessel wall.
Exploring the Reliability of the Modified Rankin Scale
Authors: Quinn Terence J. , Dawson Jesse , Walters Matthew R. , Lees Kennedy R.
Published: January 2009

Background and Purpose—

The modified Rankin Scale (mRS) is the most prevalent outcome measure in stroke trials. Use of the mRS may be hampered by variability in grading. Previous estimates of the properties of the mRS have used diverse methodologies and may not apply to contemporary trial populations. We used a mock clinical trial design to explore inter- and intraobserver variability of the mRS.

Methods—

Consenting patients with stroke attending for outpatient review had the mRS performed by 2 independent assessors with pairs of assessors selected from a team of 3 research nurses and 4 stroke physicians. Before formal assessment, interviewers estimated disability based only on initial patient observation. Each patient was then randomized to undergo the mRS using standard assessment or a prespecified structured interview. The second interviewer in the pair reassessed the patient using the same method blinded to the colleague’s score. For each patient assessed, one rater was randomly assigned to video record their interview. After 3 months, this interviewer reviewed and regraded their original video assessment.

Results—

Across 100 paired assessments, interobserver agreement was moderate (
k
=0.57). Intraobserver variability was good (
k
=0.72) but less than would be expected from previous literature. Forty-nine assessments were performed using the structured interview approach with no significant difference between structured and standard mRS. Researchers were unable to reliably predict mRS from initial limited patient assessment (
k
=0.16).

Conclusions—

Despite availability of training and structured interview, there remains substantial interobserver variability in mRS grades awarded even by experienced researchers. Additional methods to improve mRS reliability are required.
A Meta-Analysis of Candidate Gene Polymorphisms and Ischemic Stroke in 6 Study Populations
Authors: Wang Xingyu , Cheng Suzanne , Brophy Victoria H. , Erlich Henry A. , Mannhalter Christine , Berger Klaus , Lalouschek Wolfgang , Browner Warren S. , Shi Yu , Ringelstein E. Bernd , Kessler Christof , Luedemann Jan , Lindpaintner Klaus , Liu Lisheng , Ridker Paul M. , Zee Robert Y.L. , Cook Nancy R.
Published: January 2009

Background and Purpose—

Ischemic stroke is a multifactorial disease with a strong genetic component. Pathways, including lipid metabolism, systemic chronic inflammation, coagulation, blood pressure regulation, and cellular adhesion, have been implicated in stroke pathophysiology, and candidate gene polymorphisms in these pathways have been proposed as genetic risk factors.

Methods—

We genotyped 105 simple deletions and single nucleotide polymorphisms from 64 candidate genes in 3550 patients and 6560 control subjects from 6 case–control association studies conducted in the United States, Europe, and China. Genotyping was performed using the same immobilized probe typing system and meta-analyses were based on summary logistic regressions for each study. The primary analyses were fixed-effects meta-analyses adjusting for age and sex with additive, dominant, and recessive models of inheritance.

Results—

Although 7 polymorphisms showed a nominal additive association, none remained statistically significant after adjustment for multiple comparisons. In contrast, after stratification for hypertension, 2 lymphotoxin-alpha polymorphisms, which are in strong linkage disequilibrium, were significantly associated among nonhypertensive individuals:
LTA
252A>G (additive model; OR, 1.41 with 95% CI, 1.20 to 1.65;
P
=0.00002) and
LTA
26Thr>Asn (OR, 1.19 with 95% CI, 1.06 to 1.34;
P
=0.003).
LTA
252A>G remained significant after adjustment for multiple testing using either the false discovery rate or by permutation testing. The 2 single nucleotide polymorphisms showed no association in hypertensive subjects (eg,
LTA
252A>G, OR, 0.93; 95% CI, 0.84 to 1.03;
P
=0.17).

Conclusions—

These observations may indicate an important role of LTA-mediated inflammatory processes in the pathogenesis of ischemic stroke.
Corticospinal Tract Pre-Wallerian Degeneration
Authors: Domi Trish , deVeber Gabrielle , Shroff Manohar , Kouzmitcheva Elizabeth , MacGregor Daune L. , Kirton Adam
Published: January 2009

Background and Purpose—

In neonatal arterial ischemic stroke, pre-Wallerian degeneration in descending corticospinal tracts (DCST) on diffusion MRI (DWI) predicts poor outcome. This signal has not been studied in older children.

Methods—

A consecutive arterial ischemic stroke cohort (1 month to 18 years) with acute DWI and >12 months of follow-up were enrolled (SickKids Children’s Stroke Program). DCST-DWI variables were quantified with a validated software technique and correlations to the Pediatric Stroke Outcome Measure were sought.

Results—

Abnormal DCST-DWI signal was detected in 20 of 29 children (69%), with 85% having motor deficits on Pediatric Stroke Outcome Measure. DCST variables correlated with hemiparesis included: (1) any abnormal signal within the course of the DCST; (2) midbrain location; (3) percentage of peduncle; (4) vertical length; and (5) relative volume affected (all
P
<0.003). Unexpectedly, abnormal DWI signal was detected in the contralesional DCST in 7 children, all with severe hemiparesis. DCST signal abnormality increased over time, outlasted infarct DWI changes, and was difficult to appreciate on visual inspection.

Conclusions—

DCST-DWI signal is an acute predictor of motor outcome in childhood stroke and can help guide management. Previously unrecognized contralesional DCST signal predicts severe hemiparesis.
Impaired Cerebral Vasomotor Activity in Spontaneous Intracerebral Hemorrhage
Authors: Diedler Jennifer , Sykora Marek , Rupp André , Poli Sven , Karpel-Massler Georg , Sakowitz Oliver , Steiner Thorsten
Published: January 2009

Background and Purpose—

Impairment of cerebrovascular autoregulation may promote secondary brain injury in acute brain insults. Until now, only limited data are available on autoregulation in patients with spontaneous intracerebral hemorrhage. In the current study, we aimed to investigate cerebrovascular reactivity and its significance for outcome in spontaneous intracerebral hemorrhage.

Methods—

We continuously recorded mean arterial pressure, intracranial pressure, and cerebral perfusion pressure for mean 95 hours in 20 patients with spontaneous intracerebral hemorrhage. The moving correlation coefficient between mean arterial pressure and intracranial pressure (pressure reactivity index), an index of cerebral vasoreactivity, was calculated from the available artifact-free monitoring time (mean, 50.4 hours).

Results—

In the univariate analysis pressure reactivity index (
r
=0.66;
P
=0.002), hemorrhage volume (
r
=0.62;
P
=0.007), cerebral perfusion pressure (
r
=−0.71;
P
=0.001), mean arterial pressure (
r
=−0.61;
P
=0.005), and hematoma growth (
r
=0.53;
P
=0.02) significantly correlated with National Institutes of Health Stroke Scale Score at discharge. In a multivariate stepwise linear regression model, pressure reactivity index remained the only independent predictor of outcome (β=0.659;
P
=0.004). In the subgroup of patients with pressure reactivity index greater than a functional threshold of >0.2, the correlation between mean cerebral perfusion pressure and outcome remained significant (
r
=−0.73;
P
=0.0102), whereas National Institutes of Health Stroke Scale Score at discharge did not correlate with cerebral perfusion pressure in patients with pressure reactivity index <0.2 (
r
=−0.05;
P
=0.9078).

Conclusions—

We found evidence for impaired cerebral vasomotor activity as measured by pressure reactivity index in patients with spontaneous intracerebral hemorrhage. We suggest that impaired cerebrovascular reactivity contributes to poor outcome in intracerebral hemorrhage patients. This effect may be mediated by fluctuations in cerebral perfusion.
The Struggle Will Not Continue
Authors: Costner Kelley L. , Daniels Kevin , Clark Marco T.
Published: January 2009

This study assesses community college faculty attitudes toward teaching African American students. A modified Teaching African American Students Survey was used to obtain community college faculty’s responses to 21 items pertaining to their willingness to teach African American students, their openness to using culture as a resource in the classroom, and their recognition of African Americans as a distinct cultural group. Results of this study revealed two significant findings. First, community college faculty were willing to teach African American students. Second, although the faculty indicated a willingness to teach African American students, they were not willing to utilize culture as a resource in the classroom.
Deadly Combat over Natural Resources
Authors: Lujala Paivi
Published: January 2009

This article empirically examines how natural resources affect the severity of armed civil conflict. It finds that drug cultivation in the conflict area is associated with less severe conflicts but that gemstone mining and oil and gas in the conflict zone production increase the severity of conflicts. Most severe are secessionist conflicts in regions with hydrocarbon production. Interestingly, oil and gas production outside the conflict zones is related to less severe conflicts. Measured at the country level, none of the resource variables has an effect on conflict severity. These results have four implications. First, availability of natural resources affects the severity of armed civil conflict. Second, the location of resources is crucial to their impact on conflict. Third, the type of resource matters. Above all, it seems that natural resources affect conflict severity by altering incentives for both the rebel group and the state.