bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular Autonomic Neuropathy in Context of Other Complications of Type 2 Diabetes Mellitus
Authors: Moţăţăianu Anca , Bălaşa Rodica , Voidăzan Septimiu , Bajkó Zoltán
Published: December 2013

The aim of this study was to investigate the relationship between cardiac autonomic neuropathy (CAN) and other micro- and macrovascular complications and risk factors for type 2 diabetes. We included, in this study, 149 patients with type 2 diabetes. We evaluated their cardiovascular risk factors, demographic data, and any major micro- and macrovascular complications of their diabetes. Assessments of CAN were based upon Ewing’s battery.Results. CAN was present in 38.9% of patients. In the CAN group, the duration of diabetes, BMI, systolic blood pressure, lipid levels, and HBA1c were all significantly higher than those in the other group. A significant association was found between CAN and retinopathy, peripheral neuropathy, ABI, and IMT. Multivariate logistic regression demonstrated that, in type 2 diabetes, the odds of CAN (OR (95% confidence intervals)) increase with the age of the patients (1.68 (1,4129–2.0025)), the average diabetes duration (0.57 (0.47–0.67)), cholesterol (1.009 (1.00-1.01)), HbA1c levels (1.88 (1.31–2.72)), peripheral neuropathy (15.47 (5.16–46.38)), BMI (1.12 (1.05–1.21)), and smoking (2.21 (1.08–4.53)).Conclusions. This study shows that CAN in type 2 diabetes is significantly associated with other macro- and microvascular complications and that there are important modifiable risk factors for its development.
The Protection of Salidroside of the Heart against Acute Exhaustive Injury and Molecular Mechanism in Rat
Authors: Wang Yunru , Xu Peng , Wang Yang , Liu Haiyan , Zhou Yuwen , Cao Xuebin
Published: December 2013

Objective. To investigate the protection of salidroside of the heart against acute exhaustive injury and its mechanism of antioxidative stress and MAPKs signal transduction.Method. Adult male SD rats were divided into four groups randomly. Cardiomyocytes ultrastructure was observed by optical microscopy and transmission electron microscopy. The contents of CK, CK-MB, LDH, MDA, and SOD were determined by ELISA method, and the phosphorylation degrees of ERK and p38 MAPK were assayed by Western blotting. Cardiac function of isolated rat heart ischemia/reperfusion was detected by Langendorff technique.Results. Salidroside reduced the myocardium ultrastructure injury caused by exhaustive swimming, decreased the contents of CK, CK-MB, and LDH, improved the LVDP, ±LV dp/dtmaxunder the basic condition, reduced the content of MDA and the phosphorylation degree of p38 MAPK, and increased the content of SOD and the phosphorylation degree of ERK in acute exhaustive rats.Conclusion. Salidroside has the protection of the heart against acute exhaustive injury. The cardioprotection is mainly mediated by antioxidative stress and MAPKs signal transduction through reducing the content of MDA, increasing the content of SOD, and increasing p-ERK and decreasing p-p38 protein expressions in rat myocardium, which might be the mechanisms of the cardioprotective effect of salidroside.
Locked Superior Dislocation of the Acromioclavicular Joint
Authors: Elamin Salma Eltoum , Sinha Apurv , Webb Mark
Published: December 2013

Acromioclavicular (AC) joint injuries account for approximately 3–5% of shoulder girdle injuries (Rockwood et al., 1998). Depending on severity of injury and direction of displacement these are classified using Rockwood classification system for AC joint dislocation. We present an unusual case presenting with locked superior dislocation of the AC joint highlighting the presentation and subsequent successful surgical management of such case. To our knowledge this has not been reported previously in literature.
The Tractor and Semitrailer Routing Considering Carbon Dioxide Emissions
Authors: Li Hongqi , Li Yanran , Zhao Qiuhong , Lu Yue , Song Qiang
Published: December 2013

The incorporation of the minimization of carbon dioxide (CO2) emissions in the VRP is important to logistics companies. The paper deals with the tractor and semitrailer routing problem with full truckload between any two depots of the network; an integer programming model with the objective of minimizing CO2emissions per ton-kilometer is proposed. A two-stage approach with the same core steps of the simulated annealing (SA) in both stages is designed. The number of tractors is provided in the first stage and the CO2emissions per ton-kilometer are then optimized in the second stage. Computational experiments on small-scale randomly generated instances supported the feasibility and validity of the heuristic algorithm. To a practical-scale problem, the SA algorithm can provide advice on the number of tractors, the routes, and the location of the central depot to realize CO2emissions decrease.
Iron Deficiency Anemia among Hospitalized Children in Konya, Turkey
Authors: Akin Fatih , Solak Ece Selma , Kilicaslan Cengizhan , Boke Saltuk Bugra , Arslan Sukru
Published: December 2013

The aim of this study was to investigate the characteristics of our hospitalized patients with the diagnosis of iron deficiency anemia (IDA) and effects of the IDA prevention project of the Turkish Ministry of Health which was started in 2004. The recommended dose of prophylactic iron supplementation was 1-2 mg/kg/day. The files of 1519 patients who were hospitalized to Konya Education and Research Hospital Pediatrics Clinic were reviewed. A total of 50 patients consisting of 35 boys and 15 girls with the mean age of 16,59 ± 1,68 months were included into the study. The prevalence of IDA was 3.29% (boys: 4.23%, girls: 2.1%). Hgb and Hct of the patients >24 months were significantly higher than those of the patients with the age of 6–12 months. Iron supplementation receiving rates were very low. Of the 28 patients older than 12 months, only 44% of them had received a full course of iron supplementation for 8 months. In conclusion, although prophylactic iron supplementation lowered the prevalences of IDA, receiving rates of iron supplementation were not adequate. While IDA is still a public health problem, prophylactic approaches should be carried out more effectively.
Upregulation of Voltage-Gated Calcium Channel Cav1.3 in Bovine Somatotropes Treated with Ghrelin
Authors: Salinas Zarate V. M. , Magdaleno Méndez A. , Domínguez Mancera B. , Rodríguez Andrade A. , Barrientos Morales M. , Cervantes Acosta P. , Hernández Beltrán A. , Romero Salas D. , Flores Hernández J. L. V. , Monjaraz Guzmán E. , Félix Grijalva D. R.
Published: December 2013

Activation of the growth hormone (GH) secretagogue receptor (GHS-R) by synthetic GH releasing peptides (GHRP) or its endogenous ligand (Ghrelin) stimulates GH release. Though much is known about the signal transduction underlying short-term regulation, there is far less information on the mechanisms that produce long-term effects. In the current report, using an enzyme-linked immunosorbent assay for GH detection and whole-cell patch-clamp recordings, we assessed the long-term actions of such regulatory factors on voltage-activated Ca2+currents in bovine somatotropes (BS) separated on a Percoll gradient and detected by immunohistochemistry. After 24 h of treatment with Ghrelin (10 nM) or GHRP-6 (100 nM) enhanced BS secretory activity; GH secretion stimulated by GHS through the activation of GHS-R because treatment with the antagonist of GHS-R (D-Lys3-GHRP-6, 10 μM) blocked the GH secretion, and the effect was dose and time dependent (24, 48, and 72 h). GH secretion stimulated by GHRP-6 was abolished by nifedipine (0.5 μM), a blocker of L-type HVA Ca2+channels, and KN-62 (10 μM), an inhibitor of Ca2+/CaM-KII. After 72 h in culture, all recorded BS exhibited two main Ca2+currents: a low voltage-activated (LVA; T-type) and a high voltage-activated (HVA; mostly dihydropyridine-sensitive L-type) current. Interestingly, HVA and LVA channels were differentially upregulated by Ghrelin. Chronic treatment with the GHS induced a significant selective increase on the Ba2+current through HVA Ca2+channels, and caused only a small increase of currents through LVA channels. The stimulatory effect on HVA current density was accompanied by an augment in maximal conductance with no apparent changes in the kinetics and the voltage dependence of the Ca2+currents, suggesting an increase in the number of functional channels in the cell membrane. Lastly, in consistency with the functional data, quantitative real-time RT-PCR revealed transcripts encoding for the Cav1.2 and Cav1.3 pore-forming subunits of L-type channels. The treatment with Ghrelin significantly increased the Cav1.3 subunit expression, suggeting that the chronic stimulation of the GHS receptor with Ghrelin or GHRP-6 increases the number of voltage-gated Ca2+channels at the cell surface of BS.
A Survey of Some Topics Related to Differential Operators
Authors: Huet Denise
Published: December 2013

This paper is the result of investigations suggested by recent publications and completes the work of Huet, 2010. The topics, which are dealt with, concern some spaces of functions and properties of solutions of linear and nonlinear, stationary and evolution differential equations, namely, existence, spectral properties, resonances, singular perturbations, boundary layers, and inertial manifolds. They are presented in the alphabetical order. The aim of this document and of Huet, 2010, is to be a useful reference for (young) researchers in mathematics and applied sciences.
Biomarkers in Japanese Encephalitis: A Review
Authors: Kant Upadhyay Ravi
Published: December 2013

JE is a flavivirus generated dreadful CNS disease which causes high mortality in various pediatric groups. JE disease is currently diagnosed by measuring the level of viral antigens and virus neutralization IgM antibodies in blood serum and CSF by ELISA. However, it is not possible to measure various disease-identifying molecules, structural and molecular changes occurred in tissues, and cells by using such routine methods. However, few important biomarkers such as cerebrospinal fluid, plasma, neuro-imaging, brain mapping, immunotyping, expression of nonstructural viral proteins, systematic mRNA profiling, DNA and protein microarrays, active caspase-3 activity, reactive oxygen species and reactive nitrogen species, levels of stress-associated signaling molecules, and proinflammatory cytokines could be used to confirm the disease at an earlier stage. These biomarkers may also help to diagnose mutant based environment specific alterations in JEV genotypes causing high pathogenesis and have immense future applications in diagnostics. There is an utmost need for the development of new more authentic, appropriate, and reliable physiological, immunological, biochemical, biophysical, molecular, and therapeutic biomarkers to confirm the disease well in time to start the clinical aid to the patients. Hence, the present review aims to discuss new emerging biomarkers that could facilitate more authentic and fast diagnosis of JE disease and its related disorders in the future.
Forecasting New Product Diffusion Using Grey Time-Delayed Verhulst Model
Authors: Wang Yuhong , Yang Shulin , Qian Wuyong , Li Xiaozhong
Published: December 2013

Taking account of the time-delayed phenomenon in diffusion of new products, we propose the time-delayed Verhulst model and then establish a grey time-delayed Verhulst model using the method of grey differential equations. The related parameter packets of this novel model are obtained under the rule of ordinary least squares (OLS). The results show that the traditional grey Verhulst model is a special example of grey time-delayed Verhulst model which can reflect the time-delayed information effectively. A practical example of market diffusion shows that the modeling accuracy is remarkably improved by using the grey time-delayed Verhulst model presented in this paper.
Mauritia flexuosaPresentsIn VitroandIn VivoAntiplatelet and Antithrombotic Activities
Authors: Fuentes Eduardo , Rodríguez-Pérez Wilson , Guzmán Luis , Alarcón Marcelo , Navarrete Simón , Forero-Doria Oscar , Palomo Iván
Published: December 2013

Fruit from the palmMauritia flexuosais one of the most important species in Peru, Venezuela, Brazil, Colombia, Bolivia, and Guyana. The present study aimed to investigate the antiplatelet and antithrombotic activities of oil extracted fromMauritia flexuosa. The fatty acid contents were determined by gas chromatography—mass spectrometry. Oil extract of peel ofMauritia flexuosawas extracted by soxhlet extraction. The oil extract inhibited platelet secretion and aggregation induced by ADP, collagen, and TRAP-6 by a concentration-dependent way (0.1 to 1 mg/mL) without the participation of the adenylyl cyclase pathway and diminished platelet rolling and firm adhesion under flow conditions. Furthermore, the oil extract induced a marked increase in the rolling speed of leukocytes retained on the platelet surface, reflecting a reduction of rolling and less adhesion. At the concentrations used, the oil extract significantly decreased platelet release of sP-selectin, an atherosclerotic-related inflammatory mediator. Oil extract inhibited thrombus growth at the same concentration as that of aspirin, a classical reference drug. Finally, the data presented herein also demonstrate for the first time to our knowledge the protective effect of oil extracted fromMauritia flexuosaon platelet activation and thrombosis formation.
Computing Hypercrossed Complex Pairings in Digital Images
Authors: Öztunç Simge , Mutlu Ali , Bildik Necdet
Published: December 2013

We consider an additive group structure in digital images and introduce the commutator in digital images. Then we calculate the hypercrossed complex pairings which generates a normal subgroup in dimension 2 and in dimension 3 by using 8-adjacencyand 26-adjacency.
Pseudoginsenoside F11, a Novel Partial PPARγAgonist, Promotes Adiponectin Oligomerization and Secretion in 3T3-L1 Adipocytes
Authors: Wu Guoyu , Yi Junyang , Liu Ling , Wang Pengcheng , Zhang Zhijie , Li Zhen
Published: December 2013

PPARγis a nuclear hormone receptor that functions as a master regulator of adipocyte differentiation and development. Full PPARγagonists, such as the thiazolidinediones (TZDs), have been widely used to treat type 2 diabetes. However, they are characterized by undesirable side effects due to their strong agonist activities. Pseudoginsenoside F11 (p-F11) is an ocotillol-type ginsenoside isolated fromPanax quinquefolium L.(American ginseng). In this study, we found that p-F11 activates PPARγwith modest adipogenic activity. In addition, p-F11 promotes adiponectin oligomerization and secretion in 3T3-L1 adipocytes. We also found that p-F11 inhibits obesity-linked phosphorylation of PPARγat Ser-273 by Cdk5. Therefore, p-F11 is a novel partial PPARγagonist, which might have the potential to be developed as a new PPARγ-targeted therapeutics for type 2 diabetes.
Optimization of Conversion Treatment on Austenitic Stainless Steel Using Experimental Designs
Authors: El Hajjaji S. , Cros C. , Aries L.
Published: December 2013

Conversion coating is commonly used as treatment to improve the adherence of ceramics films. The conversion coating properties depend on the structure of alloy as well as on the treatment parameters. These conversion coatings must be characterized by strong interfacial adhesion, high roughness, and high real surface area, which were measured by an electrochemical method. The influence of all the elaboration factors (temperature, time, and bath composition: sulphuric acid, thiosulphate as accelerator, propargyl alcohol as inhibitor, and surface state) and also the interactions between these factors were evaluated, using statistical experimental design. The specific surface area and optical factor (α) correspond to the quantitative responses. The evaluation showed, by using a designed experimental procedure, that the most important factor was “surface state.” Sanded surface allows the formation of conversion coating with high real surface area. A further aim was to optimise two parameters: treatment time and temperature using Doehlert shell design and simplex method. The growth of the conversion coating is also influenced by treatment time and temperature. With such optimized conditions, the real surface area of conversion coating obtained was about 235 m2/m2.
Periodicity and Permanence of a Discrete Impulsive Lotka-Volterra Predator-Prey Model Concerning Integrated Pest Management
Authors: Tan Chang , Cao Jun
Published: December 2013

By piecewise Euler method, a discrete Lotka-Volterra predator-prey model with impulsive effect at fixed moment is proposed and investigated. By using Floquets theorem, we show that a globally asymptotically stable pest-eradication periodic solution exists when the impulsive period is less than some critical value. Further, we prove that the discrete system is permanence if the impulsive period is larger than some critical value. Finally, some numerical experiments are given.
BCB-Si Based Wide Band Millimeter Wave Antenna Fed by Substrate Integrated Waveguide
Authors: Vettikalladi Hamsakutty , Alkanhal Majeed A. S.
Published: December 2013

A benzocyclobutene (BCB) silicon (Si) based wideband antenna for millimeter wave applications is presented. The antenna consists of multilayer with one layer of BCB and the remaining three layers of Si. A patch is etched on the Si substrate above the air gap, which is excited through a slot. This architecture of slot, air gap, and patch will produce wide bandwidth by merging each one of resonances. The simulated results show that the antenna provides anS11<-10 dB bandwidth of 9.7 GHz (17%) starting from 51.5 GHz to 61.2 GHz around 57 GHz central frequency. The antenna provides a maximum gain of 8.9 dBi with an efficiency of 70%.
Constructing the Lyapunov Function through Solving Positive Dimensional Polynomial System
Authors: Ji Zhenyi , Wu Wenyuan , Feng Yong , Zhang Guofeng
Published: December 2013

We propose an approach for constructing Lyapunov function in quadratic form of a differential system. First, positive polynomial system is obtained via the local property of the Lyapunov function as well as its derivative. Then, the positive polynomial system is converted into an equation system by adding some variables. Finally, numerical technique is applied to solve the equation system. Some experiments show the efficiency of our new algorithm.
Blockade of 4-1BB and 4-1BBL Interaction Reduces Obesity-Induced Skeletal Muscle Inflammation
Authors: Le Ngoc Hoan , Kim Chu-Sook , Tu Thai Hien , Choi Hye-Sun , Kim Byung-Sam , Kawada Teruo , Goto Tsuyoshi , Park Taesun , Yoon Park Jung Han , Yu Rina
Published: December 2013

Obesity-induced skeletal muscle inflammation is characterized by increased macrophage infiltration and inflammatory cytokine production. In this study, we investigated whether 4-1BB, a member of the TNF receptor superfamily (TNFRSF9) that provides inflammatory signals, participates in obesity-induced skeletal muscle inflammation. Expression of the 4-1BB gene, accompanied by increased levels of inflammatory cytokines, was markedly upregulated in the skeletal muscle of obese mice fed a high-fat diet, in muscle cells treated with obesity factors, and in cocultured muscle cells/macrophages. In vitro stimulation of 4-1BB with agonistic antibody increased inflammatory cytokine levels in TNFα-pretreated muscle cells, and this effect was absent in cells derived from 4-1BB-deficient mice. Conversely, disruption of the interaction between 4-1BB and its ligand (4-1BBL) with blocking antibody decreased the release of inflammatory cytokines from cocultured muscle cells/macrophages. Moreover, deficiency of 4-1BB markedly reduced macrophage infiltration and inflammatory cytokine production in the skeletal muscle of mice fed a high-fat diet. These findings indicate that 4-1BB mediates the inflammatory responses in obese skeletal muscle by interacting with its ligand 4-1BBL on macrophages. Therefore, 4-1BB and 4-1BBL may be useful targets for prevention of obesity-induced inflammation in skeletal muscle.
Transit Station Congestion Index Research Based on Pedestrian Simulation and Gray Clustering Evaluation
Authors: Wang Shu-wei , Sun Li-shan , Rong Jian , Yang Zi-fan
Published: December 2013

A congestion phenomenon in a transit station could lead to low transfer efficiency as well as a hidden danger. Effective management of congestion phenomenon shall help to reduce the efficiency decline and danger risk. However, due to the difficulty in acquiring microcosmic pedestrian density, existing researches lack quantitative indicators to reflect congestion degree. This paper aims to solve this problem. Firstly, platform, stair, transfer tunnel, auto fare collection (AFC) machine, and security check machine were chosen as key traffic facilities through large amounts of field investigation. Key facilities could be used to reflect the passenger density of a whole station. Secondly, the pedestrian density change law of each key traffic facility was analyzed using pedestrian simulation, and the load degree calculating method of each facility was defined, respectively, afterwards. Taking pedestrian density as basic data and gray clustering evaluation as algorithm, an index called Transit Station Congestion Index (TSCI) was constructed to reflect the congestion degree of transit stations. Finally, an evaluation demonstration was carried out with five typical transit transfer stations in Beijing, and the evaluation results show that TSCI can objectively reflect the congestion degree of transit stations.
An Evaluation of Data Collected by Middle School and College-Level Students in Stream Channel Geomorphic Assessment
Authors: Lafrenz Martin D.
Published: December 2013

This project tested the accuracy and repeatability of geomorphic stream channel assessments conducted by two different middle school classes from the Walt Morey Middle School in Troutdale, OR and college students from Portland State University in Portland, OR. Each group surveyed the same three cross-sections in Fairview Creek, a tributary to the Lower Columbia River, in order to assess stream channel geometry, discharge, composition of the bed material, and water quality. The three student groups were all able to accurately document the stream channel geometry, including stream width and mean depth, indicating that these data can be successfully collected by volunteers of various ages. However, stream velocity obtained using the float method was consistently overestimated leading to a biased calculation of discharge, and the low precision of the measurements did not allow for a correction of the bias. The median particle size of the bed material determined by a pebble count was also overestimated by each group, but the low precision also negated the possibility of correcting the estimate. The stored fine sediment in the bed was underestimated by each group and again with low precision. The temperature, pH, and conductivity measured with a calibrated multimeter were accurate and precise for all groups.
Empirical Evidence on Time-Varying Hedging Effectiveness of Emissions Allowances under Departures from the Cost-of-Carry Theory
Authors: Chang Kai
Published: December 2013

Under departures from the cost-of-carry theory, traded spot prices and conditional volatility disturbed from futures market have significant impacts on futures price of emissions allowances, and then we propose time-varying hedge ratios and hedging effectiveness estimation using ECM-GARCH model. Our empirical results show that conditional variance, conditional covariance, and their correlation between between spot and futures prices exhibit time-varying trends. Conditional volatility of spot prices, conditional volatility disturbed from futures market, and conditional correlation of market noises implied from spot and futures markets have significant effects on time-varying hedge ratios and hedging effectiveness. In the immature emissions allowances market, market participants optimize portfolio sizes between spot and futures assets using historical market information and then achieve higher risk reduction of assets portfolio revenues; accordingly, we can obtain better hedging effectiveness through time-varying hedge ratios with departures from the cost-of-carry theory.
A Proper-Orthogonal Decomposition Variational Multiscale Approximation Method for a Generalized Oseen Problem
Authors: Roop John Paul
Published: December 2013

We introduce the variational multiscale (VMS) stabilization for the reduced-order modeling of incompressible flows. It is well known that the proper orthogonal decomposition (POD) technique in reduced-order modeling experiences numerical instability when applied to complex flow problems. In this case a POD discretization naturally separates out structures which corresponding to the energy cascade on large and small scales, in order, a VMS approach is natural. In this paper, we provide the mathematical background necessary for implementing VMS to a POD-Galerkin model of a generalized Oseen problem. We provide theoretical evidence which indicates the consistency of utilizing a VMS approach in the stabilization of reduced order flows. In addition we provide numerical experiments indicating that VMS improves fidelity in reproducing the qualitative properties of the flow.
Application of SNP Microarrays to the Genome-Wide Analysis of Chromosomal Instability in Premalignant Airway Lesions
Authors: Nakachi Ichiro , Rice Jessica L. , Coldren Christopher D. , Edwards Michael G. , Stearman Robert S. , Glidewell Steven C. , Varella-Garcia Marileila , Franklin Wilbur A. , Keith Robert L. , Lewis Marina T. , Gao Bifeng , Merrick Daniel T. , Miller York E. , Geraci Mark W.
Published: December 2013

Chromosomal instability is central to the process of carcinogenesis. The genome-wide detection of somatic chromosomal alterations (SCA) in small premalignant lesions remains challenging because sample heterogeneity dilutes the aberrant cell information. To overcome this hurdle, we focused on the B allele frequency data from single-nucleotide polymorphism microarrays (SNP arrays). The difference of allelic fractions between paired tumor and normal samples from the same patient (delta-θ) provides a simple but sensitive detection of SCA in the affected tissue. We applied the delta-θ approach to small, heterogeneous clinical specimens, including endobronchial biopsies and brushings. Regions identified by delta-θ were validated by FISH and quantitative PCR in heterogeneous samples. Distinctive genomic variations were successfully detected across the whole genome in all invasive cancer cases (6 of 6), carcinoma in situ (3 of 3), and high-grade dysplasia (severe or moderate; 3 of 11). Not only well-described SCAs in lung squamous cell carcinoma, but also several novel chromosomal alterations were frequently found across the preinvasive dysplastic cases. Within these novel regions, losses of putative tumor suppressors (RNF20 and SSBP2) and an amplification of RASGRP3 gene with oncogenic activity were observed. Widespread sampling of the airway during bronchoscopy demonstrated that field cancerization reflected by SCAs at multiple sites was detectable. SNP arrays combined with delta-θ analysis can detect SCAs in heterogeneous clinical sample and expand our ability to assess genomic instability in the airway epithelium as a biomarker of lung cancer risk. Cancer Prev Res; 7(2); 255–65. ©2013 AACR.
Preventive Effects of NSAIDs, NO-NSAIDs, and NSAIDs Plus Difluoromethylornithine in a Chemically Induced Urinary Bladder Cancer Model
Authors: Nicastro Holly L. , Grubbs Clinton J. , Margaret Juliana M. , Bode Ann M. , Kim Mi-Sung , Lu Yan , You Ming , Milne Ginger L. , Boring Daniel , Steele Vernon E. , Lubet Ronald A.
Published: December 2013

Urinary bladder cancer prevention studies were performed with the nonsteroidal anti-inflammatory drugs (NSAID) naproxen (a standard NSAID with a good cardiovascular profile), sulindac, and their nitric oxide (NO) derivatives. In addition, the effects of the ornithine decarboxylase inhibitor, difluoromethylornithine (DFMO), alone or combined with a suboptimal dose of naproxen or sulindac was examined. Agents were evaluated at their human equivalent doses (HED), as well as at lower doses. In the hydroxybutyl(butyl)nitrosamine (OH-BBN) model of urinary bladder cancer, naproxen (400 or 75 ppm) and sulindac (400 ppm) reduced the incidence of large bladder cancers by 82%, 68%, and 44%, respectively, when the agents were initially given 3 months after the final dose of the carcinogen; microscopic cancers already existed. NO-naproxen was highly effective, whereas NO-sulindac was inactive. To further compare naproxen and NO-naproxen, we examined their effects on gene expression in rat livers following a 7-day exposure. Limited, but similar, gene expression changes in the liver were induced by both agents, implying that the primary effects of both are mediated by the parent NSAID. When agents were initiated 2 weeks after the last administration of OH-BBN, DFMO at 1,000 ppm had limited activity, a low dose of naproxen (75 ppm) and sulindac (150 ppm) were highly and marginally effective. Combining DFMO with suboptimal doses of naproxen had minimal effects, whereas the combination of DMFO and sulindac was more active than either agent alone. Thus, naproxen and NO-naproxen were highly effective, whereas sulindac was moderately effective in the OH-BBN model at their HEDs. Cancer Prev Res; 7(2); 246–54. ©2013 AACR.
Selective BCL-2 Inhibition by ABT-199 Causes On-Target Cell Death in Acute Myeloid Leukemia
Authors: Pan Rongqing , Hogdal Leah J. , Benito Juliana M. , Bucci Donna , Han Lina , Borthakur Gautam , Cortes Jorge , DeAngelo Daniel J. , Debose LaKeisha , Mu Hong , Döhner Hartmut , Gaidzik Verena I. , Galinsky Ilene , Golfman Leonard S. , Haferlach Torsten , Harutyunyan Karine G. , Hu Jianhua , Leverson Joel D. , Marcucci Guido , Müschen Markus , Newman Rachel , Park Eugene , Ruvolo Peter P. , Ruvolo Vivian , Ryan Jeremy , Schindela Sonja , Zweidler-McKay Patrick , Stone Richard M. , Kantarjian Hagop , Andreeff Michael , Konopleva Marina , Letai Anthony G.
Published: December 2013

B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. Here, we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199. In primary patient cells, the median IC50 was approximately 10 nmol/L, and cell death occurred within 2 hours. Our ex vivo sensitivity results compare favorably with those observed for chronic lymphocytic leukemia, a disease for which ABT-199 has demonstrated consistent activity in clinical trials. Moreover, mitochondrial studies using BH3 profiling demonstrate activity at the mitochondrion that correlates well with cytotoxicity, supporting an on-target mitochondrial mechanism of action. Our protein and BH3 profiling studies provide promising tools that can be tested as predictive biomarkers in any clinical trial of ABT-199 in AML.

Significance: Although targeting BCL-2 has largely been investigated in lymphoid cancers, we present preclinical results of targeting BCL-2 in AML. These results support clinical testing of the small-molecule BCL-2 antagonist ABT-199 in AML, accompanied by testing of predictive biomarkers used in this study. Cancer Discov; 4(3); 362–75. ©2013 AACR.

See related commentary by Hockenbery, p. 278

This article is highlighted in the In This Issue feature, p. 259
Kmasker - A Tool for in silico Prediction of Single-Copy FISH Probes for the Large-Genome Species Hordeum vulgare
Authors: Schmutzer T. , Ma L. , Pousarebani N. , Bull F. , Stein N. , Houben A. , Scholz U.
Published: December 2013

Specific localization of large genomic fragments by fluorescence in situ hybridization (FISH) is challenging in large- genome plant species due to the high content of repetitive sequences. We report the automated work flow (Kmasker) for in silico extraction of unique genomic sequences of large genomic fragments suitable for FISH in barley. This method can be widely used for the integration of genetic and cytogenetic maps in plants and other species with large and complex genomes if the probe sequence (e.g. BACs, sequence contigs) and a low coverage (8-fold) of unassembled sequences of the species of interest are available. Kmasker has been made publicly available as a web tool at http://webblast.ipk-gatersleben.de/kmasker.
Shunting in Acute Cerebral Venous Thrombosis: A Systematic Review
Authors: Lobo S. , Ferro J.M. , Barinagarrementeria F. , Bousser M.G. , Canhão P. , Stam J. ,   ISCVT Investigators
Published: December 2013

Background and Purpose: The efficacy of cerebrospinal fluid shunting to reduce intracranial hypertension and prevent fatal brain herniation in acute cerebral venous thrombosis (CVT) is unknown. Method: From the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) and a systematic literature review, we retrieved acute CVT patients treated only with shunting (external ventricular drain, ventriculoperitoneal or ventriculojugular shunt). Outcome was classified at 6 months and final follow-up by the modified Rankin Scale (mRS). Results: 15 patients were collected (9 from the ISCVT and 6 from the review) who were treated with a shunt (external ventricular drain in 6 patients, a ventriculoperitoneal shunt in 8 patients or an unspecified type of shunt in another one). Eight patients (53.3%) regained independence (mRS 0-2), while 2 patients (13.3%) were left with a severe handicap (mRS 4-6) and 4 (26.7%) died despite treatment. Five patients with parenchymal lesions were shunted within 48 h from admission deterioration, 4 with an external ventricular drain: 2 (40%) recovered to independence, 2 (40%) had a severe handicap and 1 (20%) died. In contrast, all 3 patients with intracranial hypertension and no parenchymal lesions receiving a ventriculoperitoneal shunt later than 48 h regained independence. Conclusion and Implications: A quarter of acute CVT patients treated with a shunt died, and only half regained independence. With the limitation of the small number of subjects, this review suggests that shunting does not appear to be effective in preventing death from brain herniation in acute CVT. We cannot exclude that shunting may benefit patients with sustained intracranial hypertension and no parenchymal lesions.
The Relative Dose Response Test Based on Retinol-Binding Protein 4 Is Not Suitable to Assess Vitamin A Status in Very Low Birth Weight Infants
Authors: Schmiedchen Bettina , Longardt Ann Carolin , Bührer Christoph , Raila Jens , Loui Andrea , Schweigert Florian J.
Published: December 2013

Background: The relative dose response (RDR) test, which quantifies the increase in serum retinol after vitamin A administration, is a qualitative measure of liver vitamin A stores. Particularly in preterm infants, the feasibility of the RDR test involving blood is critically dependent on small sample volumes. Objectives: This study aimed to assess whether the RDR calculated with retinol-binding protein 4 (RBP4) might be a substitute for the classical retinol-based RDR test for assessing vitamin A status in very preterm infants. Methods: This study included preterm infants with a birth weight below 1,500 g (n = 63, median birth weight 985 g, median gestational age 27.4 weeks) who were treated with 5,000 IU retinyl palmitate intramuscularly 3 times a week for 4 weeks. On day 3 (first vitamin A injection) and day 28 of life (last vitamin A injection), the RDR was calculated and compared using serum retinol and RBP4 concentrations. Results: The concentrations of retinol (p < 0.001) and RBP4 (p < 0.01) increased significantly from day 3 to day 28. On day 3, the median (IQR) retinol-RDR was 27% (8.4-42.5) and the median RBP4-RDR was 8.4% (-3.4 to 27.9), compared to 7.5% (-10.6 to 20.8) and -0.61% (-19.7 to 15.3) on day 28. The results for retinol-RDR and RBP4-RDR revealed no significant correlation. The agreement between retinol-RDR and RBP4-RDR was poor (day 3: Cohen's κ = 0.12; day 28: Cohen's κ = 0.18). Conclusion: The RDR test based on circulating RBP4 is unlikely to reflect the hepatic vitamin A status in preterm infants.
Perinatal Outcomes of Pregnancies Complicated by Maternal Depression with or without Selective Serotonin Reuptake Inhibitor Therapy
Authors: Engelstad Holly J. , Roghair Robert D. , Calarge Chadi A. , Colaizy Tarah T. , Stuart Scott , Haskell Sarah E.
Published: December 2013

Background: Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed psychotropics for major depressive disorder during pregnancy and are used in up to 6.2% of pregnancies. Objective: To compare the perinatal outcomes of pregnancies complicated by maternal depression with or without SSRI therapy versus nondepressed pregnancies. Methods: International Classification of Diseases (ICD)-9 codes for depression were identified among women who delivered at the University of Iowa from April 2009 to March 2011. Data were extracted from linked maternal-neonatal records for all charts with an ICD-9 code for depression and an equal number of women without ICD-9 codes for depression. Results: Of the 3,695 women who delivered between 2009 and 2011, 238 had an ICD-9 code for depression. Sixteen women had depression listed in their records but did not have an ICD-9 code for depression. Their data were combined with those of the women with ICD-9 codes for depression, and it was found that 126 women (50%) in this combined depression cohort received an SSRI. Women with depression had increased alcohol and tobacco use, BMI and premature delivery rates (p < 0.01). Maternal depression was associated with an increased frequency of neonatal intensive care unit (NICU) admission (p < 0.001). In addition to depression, maternal SSRI use, obesity and smoking were univariate predictors of NICU admission. Conclusions: Among women with depression, the use of an SSRI was not associated with significant differences in any of the measured maternal or neonatal parameters, but further studies are needed to evaluate the specific effects of SSRI exposure in early or late gestation. Despite SSRI utilization, women with depression continue to have increased risks during pregnancy.
Changes in Geographic Variation in the Use of Percutaneous Coronary Intervention for Stable Ischemic Heart Disease After Publication of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Trial
Authors: Mohan Arun V. , Fazel Reza , Huang Pei-Hsiu , Shen Yu-Chu , Howard David
Published: December 2013

Background—

Clinical uncertainty is cited as a cause of geographic variation. However, little is known about the effect of comparative effectiveness research on variation. We examined whether geographic variation in the use of percutaneous coronary intervention (PCI) for stable ischemic heart disease (SIHD) declined after publication of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial.

Methods and Results—

We examined changes in utilization and geographic variation in 67 hospital referral regions using the State Inpatient Databases. We compared age- and sex-adjusted rates of PCI for SIHD before (2006) and after (2008) publication of the COURAGE trial and compared those with contemporaneous changes in PCI volume for acute coronary syndrome. A total of 272 659 PCIs for SIHD from 526 hospitals were included in the analysis. After the publication of the COURAGE trial, PCI volume for SIHD declined by 25% (
P
<0.001) and decreased by 12% for acute coronary syndrome (
P
<0.001). This was predominantly attributable to changes in hospital referral regions with the highest levels of utilization pre-COURAGE trial (35% decline in the highest tertile versus 18% in the lowest). As measured by the systematic component of variation, there was substantial geographic variation in the use of PCI for SIHD preceding the publication of the COURAGE trial. Variation declined by 28% (0.53 versus 0.40) after publication, but geographic variation remained higher for SIHD than acute coronary syndrome (0.40 versus 0.17).

Conclusions—

There was a substantial decline in the use of and geographic variation in PCI for SIHD after the publication of the COURAGE trial. However, geographic variation in the use of PCI for SIHD remained high.
Cortical Photothrombotic Infarcts Impair the Recall of Previously Acquired Memories but Spare the Formation of New Ones
Authors: Diederich Kai , Schmidt Antje , Strecker Jan-Kolja , Schäbitz Wolf-Rüdiger , Schilling Matthias , Minnerup Jens
Published: December 2013

Background and Purpose—

Despite a high incidence of poststroke dementia, there is no specific treatment for this condition. Because the evaluation of poststroke cognitive deficits in animal models of stroke is exceedingly challenging, the preclinical evaluation of candidate drugs is limited. We aimed to explore the impact of small cortical photothrombotic strokes on poststroke cognition, thereby assessing the suitability of this experimental stroke model for the investigation of cognitive impairment after stroke.

Methods—

Photothrombotic cortical infarcts were induced in 19 adult male Wistar rats. Nineteen sham-operated animals served as controls. Using the Morris water maze, we analyzed the impact of photothrombotic stroke on both the acquisition of new memories and the recall of previously acquired memories. The cylinder test, the adhesive tape removal test, and the rotarod test were performed to investigate sensorimotor deficits.

Results—

Photothrombotic stroke significantly impaired the recall of previously acquired memories (
P
<0.05), whereas the acquisition of new memories remained largely intact. The analysis of the animals’ swimming speed in the water maze and the rotarod test showed no confounding motor impairments after photothrombotic stroke. The adhesive tape removal test and the cylinder test revealed mild sensorimotor deficits in lesioned animals (
P
<0.05).

Conclusions—

Photothrombotic cortical infarcts impair the recall of memories acquired before stroke, whereas the formation of new memories remains unimpaired. The observed deficits in the water maze are not confounded by disturbed motor functions. Overall, experimental photothrombotic strokes are well suited for the investigation of specific cognitive impairments after stroke.
Taxonomic Review of the Genus Rhinoncomimus (Coleoptera: Curculionidae: Ceutorhynchinae) with description of a new species from Yunnan, China
Authors: HUANG JUNHAO , YOSHITAKE HIRAKU , ZHANG RUNZHI , ITO MOTOMI
Published: December 2013

The genus Rhinoncomimus Wagner, 1940 includes seven species from Eastern Asia. One new species, Rh. continuus sp. nov. from Yunnan, China, is described. Habitus photos, illustrations and descriptions of all species except Rh. rubripes Korotyaev, 2006 (a possible junior synonym of R. niger Chûjô and Morimoto, 1959) are provided in detail, as well as key to species and distribution maps. In addition, the host plant of the type species Rh. klapperichi Wagner, 1940, Polygonum hydropiper L. (Polygonaceae) is newly recorded.
Two new species of the genus Cicadatra Kolenati (Hemiptera: Cicadidae) from Pakistan
Authors: AHMED ZUBAIR , SANBORN ALLEN F , AKHTER MUHAMMAD ATIQUE
Published: December 2013

Two new species of the genus Cicadatra Kolenati, C. ashrafi sp.n. and C. tandojamensis sp.n. are described from Pakistan. Male genitalia, timbals and opercula are described and illustrated as important diagnostic characters. Host affinity for one species is also provided. A key to the known species of Pakistani Cicadatra is also given.
Multiyear Volume, Liquid Freshwater, and Sea Ice Transports through Davis Strait, 2004–10*
Authors: Curry B. , Lee C. M. , Petrie B. , Moritz R. E. , Kwok R.
Published: December 2013

Davis Strait is a primary gateway for freshwater exchange between the Arctic and North Atlantic Oceans including freshwater contributions from west Greenland and Canadian Arctic Archipelago glacial melt. Data from six years (2004–10) of continuous measurements collected by a full-strait moored array and concurrent high-resolution Seaglider surveys are used to estimate volume and liquid freshwater transports through Davis Strait, with respective annual averages of −1.6 ± 0.5 Sverdrups (Sv; 1 Sv ≡ 106 m3 s−1) and −93 ± 6 mSv (negative sign indicates southward transport). Sea ice export contributes an additional −10 ± 1 mSv of freshwater transport, estimated using satellite ice area transport and moored upward-looking sonar ice thickness measurements. Interannual and annual variability of the net transports are large, with average annual volume and liquid freshwater transport standard deviations of 0.7 Sv and 17 mSv and with interannual standard deviations of 0.3 Sv and 15 mSv. Moreover, there are no clear trends in the net transports over the 6-yr period. However, salinity in the upper 250 m between Baffin Island and midstrait decreases starting in September 2009 and remains below average through August 2010, but appears to return to normal by the end of 2010. This freshening event, likely caused by changes in arctic freshwater storage, is not apparent in the liquid freshwater transport time series due to a reduction in southward volume transport in 2009–10. Reanalysis of Davis Strait mooring data from the period 1987–90, compared to the 2004–10 measurements, reveals less arctic outflow and warmer, more saline North Atlantic inflow during the most recent period.
Courthouse Violence: The View from the Bench
Authors: Geiger Fred A.
Published: December 2013

Courthouse violence can be divided into two broad categories: incidents that are opportunistic and unpremeditated and those that are premeditated. With planning and adequate security measures, opportunistic incidents can be greatly diminished, but it is difficult to be secure from premeditated incidents. Providing sufficient security to make courthouses safe is not a simple matter. Our justice system rests upon acceptance of the impartiality, fairness, and independence of our judiciary. Too much security undermines that image if it appears that our courts are being held hostage by violence and threats of violence. Too little security, however, leads to a lack of general respect for the law if order cannot be maintained. The challenge is to effect appropriate defenses without compromising the justice system.
Pathway to Political Participation
Authors: Moeller Judith , de Vreese Claes , Esser Frank , Kunz Ruth
Published: December 2013

News media play a key role in informing young citizens about politics and cultivating a sense of political efficacy. Online news media, in particular, are expected to have a positive impact due to their interactivity and new opportunities to share and discuss information. This study analyzes the impact of online and offline news media use on the growth in internal efficacy among adolescents, based on data we collected in a three-wave panel survey in the Netherlands ( N = 729). Additionally, we test the impact of internal efficacy on turnout using a fourth wave of the same sample ( N = 612). The results show that while newspaper reading has the strongest effects among traditional news sources, actively participating in the communication process of political information online has the strongest impact on internal efficacy. Internal efficacy in turn is found to be a significant predictor of first-time voters. The article concludes with a discussion of media use as a pathway to political participation through internal political efficacy.