bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiofilm Activity, Compound Characterization, and Acute Toxicity of Extract from a Novel Bacterial Species ofPaenibacillus
Authors: Alasil Saad Musbah , Omar Rahmat , Ismail Salmah , Yusof Mohd Yasim
Published: March 2014

The effectiveness of many antimicrobial agents is currently decreasing; therefore, it is important to search for alternative therapeutics. Our study was carried out to assess thein vitroantibiofilm activity using microtiter plate assay, to characterize the bioactive compounds using Ultra Performance Liquid Chromatography-Diode Array Detection and Liquid Chromatography-Mass Spectrometry and to test the oral acute toxicity on Sprague Dawley rats of extract derived from a novel bacterial species ofPaenibacillusstrain 139SI. Our results indicate that the crude extract and its three identified compounds exhibit strong antibiofilm activity against a broad range of clinically important pathogens. Three potential compounds were identified including an amino acid antibiotic C8H20N3O4P (MW 253.237), phospholipase A2 inhibitor C21H36O5(MW 368.512), and an antibacterial agent C14H11N3O2(MW 253.260). The acute toxicity test indicates that the mortality rate among all rats was low and that the biochemical parameters, hematological profile, and histopathology examination of liver and kidneys showed no significant differences between experimental groupsP>0.05. Overall, our findings suggest that the extract and its purified compounds derived from novelPaenibacillussp. are nontoxic exhibiting strong antibiofilm activity against Gram-positive and Gram-negative pathogens that can be useful towards new therapeutic management of biofilm-associated infections.
From Structure to Catalysis: Recent Developments in the Biotechnological Applications of Lipases
Authors: Anobom Cristiane D. , Pinheiro Anderson S. , De-Andrade Rafael A. , Aguieiras Erika C. G. , Andrade Guilherme C. , Moura Marcelo V. , Almeida Rodrigo V. , Freire Denise M.
Published: March 2014

Microbial lipases are highly appreciated as biocatalysts due to their peculiar characteristics such as the ability to utilize a wide range of substrates, high activity and stability in organic solvents, and regio- and/or enantioselectivity. These enzymes are currently being applied in a variety of biotechnological processes, including detergent preparation, cosmetics and paper production, food processing, biodiesel and biopolymer synthesis, and the biocatalytic resolution of pharmaceutical derivatives, esters, and amino acids. However, in certain segments of industry, the use of lipases is still limited by their high cost. Thus, there is a great interest in obtaining low-cost, highly active, and stable lipases that can be applied in several different industrial branches. Currently, the design of specific enzymes for each type of process has been used as an important tool to address the limitations of natural enzymes. Nowadays, it is possible to “order” a “customized” enzyme that has ideal properties for the development of the desired bioprocess. This review aims to compile recent advances in the biotechnological application of lipases focusing on various methods of enzyme improvement, such as protein engineering (directed evolution and rational design), as well as the use of structural data for rational modification of lipases in order to create higher active and selective biocatalysts.
Grisel’s Syndrome: A Rare Complication following Adenotonsillectomy
Authors: Bucak Abdulkadir , Ulu Sahin , Aycicek Abdullah , Kacar Emre , Miman Murat Cem
Published: March 2014

Grisel’s syndrome is a nontraumatic atlantoaxial subluxation which is usually secondary of an infection or an inflammation at the head and neck region. It can be observed after surgery of head and neck region. Etiopathogenesis has not been clearly described yet, but increased looseness of paraspinal ligament is thought to be responsible. Patients typically present with painful torticollis. Diagnosis of Grisel’s syndrome is largely based on suspicion of the patient who has recently underwent surgery or history of infection in head and neck region. Physical examination and imaging techniques assist in diagnosis. Therefore, clinicians should be aware of acute nontraumatic torticollis after recently applied the head and neck surgery or undergone upper respiratory tract infection. In this paper, a case of an eight-year-old male patient who had Grisel’s syndrome after adenotonsillectomy is discussed with review of the literature.
Polymorphisms in the Tumor Necrosis Factor Receptor Genes Affect the Expression Levels of Membrane-Bound Type I and Type II Receptors
Authors: Sennikov Sergey V. , Vasilyev Filipp F. , Lopatnikova Julia A. , Shkaruba Nadezhda S. , Silkov Alexander N.
Published: March 2014

The level of TNF receptors on various cells of immune system and its association with the gene polymorphism were investigated. Determining the levels of membrane-bound TNFαreceptors on peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry using BD QuantiBRITE calibration particles. Soluble TNFαreceptor (sTNFRs) levels were determined by ELISA and genotyping was determined by PCR-RFLP. Homozygous TT individuals at SNP-609G/T TNFRI (rs4149570) showed lower levels of sTNFRI compared to GG genotype carriers. Homozygous carriers of CC genotype at SNP-1207G/C TNFRI (rs4149569) had lower expression densities of membrane-bound TNFRI on intact CD14+monocytes compared to individuals with the GC genotype. The frequency differences in the CD3+and CD19+cells expressing TNFRII in relation to SNP-1709A/TTNFRII(rs652625) in healthy individuals were also determined. The genotype CC in SNP −3609C/TTNFRII(rs590368) was associated with a lower percentage of CD14+cells expressing TNFRII compared to individuals with the CT genotype. Patients with rheumatoid arthritis had no significant changes in the frequencies of genotypes. Reduced frequency was identified for the combination TNFRI-609GT + TNFRII-3609CC only. The polymorphisms in genes represent one of cell type-specific mechanisms affecting the expression levels of membrane-bound TNFαreceptors and TNFα-mediated signaling.
Efficient Dynamic Replication Algorithm Using Agent for Data Grid
Authors: Vashisht Priyanka , Kumar Rajesh , Sharma Anju
Published: March 2014

In data grids scientific and business applications produce huge volume of data which needs to be transferred among the distributed and heterogeneous nodes of data grids. Data replication provides a solution for managing data files efficiently in large grids. The data replication helps in enhancing the data availability which reduces the overall access time of the file. In this paper an algorithm, namely, EDRA using agents for data grid, has been proposed and implemented. EDRA consists of dynamic replication of hierarchical structure taken into account for the selection of best replica. Decision for selecting the best replica is based on scheduling parameters. The scheduling parameters are bandwidth, load gauge, and computing capacity of the node. The scheduling in data grid helps in reducing the data access time. The distribution of the load on the nodes of data grid is done evenly by considering scheduling parameters. EDRA is implemented using data grid simulator, namely, OptorSim. European Data Grid CMS test bed topology is used in this experiment. The simulation results are obtained by comparing BHR, LRU, No Replication, and EDRA. The result shows the efficiency of EDRA algorithm in terms of mean job execution time, network usage, and storage usage of node.
Kinetics and Mechanism of the Oxidation of Naphthol Green B by Peroxydisulphate Ion in Aqueous Acidic Medium
Authors: Myek B. , Idris S. O. , Iyun J. F.
Published: March 2014

The kinetics of the oxidation of naphthol green B (NGB3−) by peroxydisulphate ion has been carried out in aqueous acidic medium at λmax of 700 nm, T=23±1°C, and I=0.50 mol dm−3 (NaCl). The reaction shows a first-order dependence on oxidant and reductant concentration, respectively. The stoichiometry of the NGB—S2O82- reaction is 1 : 2. Change in hydrogen ions concentration of the reaction medium has no effect on the rate of the reaction. Added cations and anions decreased the rate of the reaction. The results of spectroscopic and kinetic investigation indicate that no intermediate complex is probably formed in the course of this reaction.
Influence of Second-Trimester Ultrasound Markers for Down Syndrome in Pregnant Women of Advanced Maternal Age
Authors: Rumi Kataguiri Mariza , Araujo Júnior Edward , Silva Bussamra Luiz Claudio , Machado Nardozza Luciano Marcondes , Fernandes Moron Antonio
Published: March 2014

The objective of the present study was to evaluate the influence of second-trimester ultrasound markers on the incidence of Down syndrome among pregnant women of advanced maternal age. This was a retrospective cohort study on 889 singleton pregnancies between the 14th and 30th weeks, with maternal age ≥ 35 years, which would undergo genetic amniocentesis. The second-trimester ultrasound assessed the following markers: increased nuchal fold thickness, cardiac hyperechogenic focus, mild ventriculomegaly, choroid plexus cysts, uni- or bilateral renal pyelectasis, intestinal hyperechogenicity, single umbilical artery, short femur and humerus length, hand/foot alterations, structural fetal malformation, and congenital heart disease. To investigate differences between the groups with and without markers, nonparametric tests consisting of the chi-square test or Fisher’s exact test were used. Moreover, odds ratios with their respective 95% confidence intervals were calculated. Out of the 889 pregnant women, 131 (17.3%) presented markers and 758 (82.7%) did not present markers on the second-trimester ultrasound. Increased nuchal fold (P<0.001) and structural malformation (P<0.001) were the markers most associated with Down syndrome. The presence of one marker increased the relative risk 10.5-fold, while the presence of two or more markers increased the risk 13.5-fold. The presence of markers on the second-trimester ultrasound, especially thickened nuchal fold and structural malformation, increased the risk of Down syndrome among pregnant women with advanced maternal age.
Convergence Analysis and Numerical Study of a Fixed-Point Iterative Method for Solving Systems of Nonlinear Equations
Authors: Huang Na , Ma Changfeng
Published: March 2014

We present a fixed-point iterative method for solving systems of nonlinear equations. The convergence theorem of the proposed method is proved under suitable conditions. In addition, some numerical results are also reported in the paper, which confirm the good theoretical properties of our approach.
Long-Term Results of Combined Tunica Albuginea Plication and Penile Prosthesis Implantation for Severe Penile Curvature and Erectile Dysfunction
Authors: Cormio Luigi , Massenio Paolo , Di Fino Giuseppe , Lucarelli Giuseppe , Mancini Vito , Liuzzi Giuseppe , Carrieri Giuseppe
Published: March 2014

Penile prosthesis implantation is the recommended treatment in patients with penile curvature and severe erectile dysfunction (ED) not responding to pharmacotherapy. Most patients with mild-to-moderate curvature can expect cylinder insertion to correct both ED and penile curvature. In patients with severe curvature and in those with persistent curvature after corporeal dilation and prosthesis placement, intraoperative penile “modelling” over the inflated prosthesis has been introduced as an effective treatment. We report for the first time the long-term results of a patient treated with combined penile plication and placement of an inflatable penile prosthesis.
Postoperative Delayed Duodenum Perforation following Elective Laparoscopic Cholecystectomy
Authors: Jing Kong , Shuo-Dong Wu
Published: March 2014

Background. Duodenum injury is extremely rare complication of laparoscopic cholecystectomy with potentially fatal consequences.Methods. Over the past 13-year period, 3000 laparoscopic cholecystectomies were performed in our institution. Duodenum injury only occurred in one patient recently who had undergone gastrectomy owing to duodenal diverticulum. The diagnosis and management of this rare complication of laparoscopic cholecystectomy are described, and the literature is reviewed.Results. We present this case of duodenum injury on the fourth postoperative day after selective laparoscopic cholecystectomy was treated successfully by percutaneous needle aspiration and catheter drainage. The hospital stay was 26 days. No abscess recurred during the follow-up period.Conclusion. Duodenum injuries are extremely rare complications of laparoscopic cholecystectomy with potentially fatal consequences if not promptly recognized and treated. Sonographically guided percutaneous needle aspiration and catheter drainage can be used to treat the intraperitoneal abscess. Billroth II subtotal gastrectomy and gastrojejunostomy were beneficial for the treatment.
Stability Analysis for Travelling Wave Solutions of the Olver and Fifth-Order KdV Equations
Authors: Seadawy A. R. , Amer W. , Sayed A.
Published: March 2014

The Olver equation is governing a unidirectional model for describing long and small amplitude waves in shallow water waves. The solitary wave solutions of the Olver and fifth-order KdV equations can be obtained by using extended tanh and sech-tanh methods. The present results are describing the generation and evolution of such waves, their interactions, and their stability. Moreover, the methods can be applied to a wide class of nonlinear evolution equations. All solutions are exact and stable and have applications in physics.
An Improved Car‐Following Model in Vehicle Networking Based on Network Control
Authors: Kong D. Y. , Xu H. Y.
Published: March 2014

Vehicle networking is a system to realize information interoperability between vehicles and people, vehicles and roads, vehicles and vehicles, and cars and transport facilities, through the network information exchange, in order to achieve the effective monitoring of the vehicle and traffic flow. Realizing information interoperability between vehicles and vehicles, which can affect the traffic flow, is an important application of network control system (NCS). In this paper, a car‐following model using vehicle networking theory is established, based on network control principle. The car‐following model, which is an improvement of the traditional traffic model, describes the traffic in vehicle networking condition. The impact that vehicle networking has on the traffic flow is quantitatively assessed in a particular scene of one‐way, no lane changing highway. The examples show that the capacity of the road is effectively enhanced by using vehicle networking.
Bioenergetics of Mammalian Sperm Capacitation
Authors: Ferramosca Alessandra , Zara Vincenzo
Published: March 2014

After ejaculation, the mammalian male gamete must undergo the capacitation process, which is a prerequisite for egg fertilization. The bioenergetics of sperm capacitation is poorly understood despite its fundamental role in sustaining the biochemical and molecular events occurring during gamete activation. Glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) are the two major metabolic pathways producing ATP which is the primary source of energy for spermatozoa. Since recent data suggest that spermatozoa have the ability to use different metabolic substrates, the main aim of this work is to present a broad overview of the current knowledge on the energy-producing metabolic pathways operating inside sperm mitochondria during capacitation in different mammalian species. Metabolism of glucose and of other energetic substrates, such as pyruvate, lactate, and citrate, is critically analyzed. Such knowledge, besides its obvious importance for basic science, could eventually translate into the development of novel strategies for treatment of male infertility, artificial reproduction, and sperm selection methods.
Characteristics of US Health Care Providers Who Counsel Adolescents on Sports and Energy Drink Consumption
Authors: Xiang Nan , Wethington Holly , Onufrak Stephen , Belay Brook
Published: March 2014

Objective. To examine the proportion of health care providers who counsel adolescent patients on sports and energy drink (SED) consumption and the association with provider characteristics.Methods. This is a cross-sectional analysis of a survey of providers who see patients ≤17 years old. The proportion providing regular counseling on sports drinks (SDs), energy drinks (EDs), or both was assessed. Chi-square analyses examined differences in counseling based on provider characteristics. Multivariate logistic regression calculated adjusted odds ratios (aOR) for characteristics independently associated with SED counseling.Results. Overall, 34% of health care providers regularly counseled on both SEDs, with 41% regularly counseling on SDs and 55% regularly counseling on EDs. On adjusted modeling regular SED counseling was associated with the female sex (aOR: 1.44 [95% CI: 1.07–1.93]), high fruit/vegetable intake (aOR: 2.05 [95% CI: 1.54–2.73]), family/general practitioners (aOR: 0.58 [95% CI: 0.41–0.82]) and internists (aOR: 0.37 [95% CI: 0.20–0.70]) versus pediatricians, and group versus individual practices (aOR: 0.59 [95% CI: 0.42–0.84]). Modeling for SD- and ED-specific counseling found similar associations with provider characteristics.Conclusion. The prevalence of regular SED counseling is low overall and varies. Provider education on the significance of SED counseling and consumption is important.
Identification and Characterization of Small Molecules That Inhibit Nonsense-Mediated RNA Decay and Suppress Nonsense p53 Mutations
Authors: Martin Leenus , Grigoryan Arsen , Wang Ding , Wang Jinhua , Breda Laura , Rivella Stefano , Cardozo Timothy , Gardner Lawrence B.
Published: March 2014

Many of the gene mutations found in genetic disorders, including cancer, result in premature termination codons (PTC) and the rapid degradation of their mRNAs by nonsense-mediated RNA decay (NMD). We used virtual library screening, targeting a pocket in the SMG7 protein, a key component of the NMD mechanism, to identify compounds that disrupt the SMG7–UPF1 complex and inhibit NMD. Several of these compounds upregulated NMD-targeted mRNAs at nanomolar concentrations, with minimal toxicity in cell-based assays. As expected, pharmacologic NMD inhibition disrupted SMG7–UPF1 interactions. When used in cells with PTC-mutated p53, pharmacologic NMD inhibition combined with a PTC “read-through” drug led to restoration of full-length p53 protein, upregulation of p53 downstream transcripts, and cell death. These studies serve as proof-of-concept that pharmacologic NMD inhibitors can restore mRNA integrity in the presence of PTC and can be used as part of a strategy to restore full-length protein in a variety of genetic diseases. Cancer Res; 74(11); 3104–13. ©2014 AACR.
Mislocalization of the Cell Polarity Protein Scribble Promotes Mammary Tumorigenesis and Is Associated with Basal Breast Cancer
Authors: Feigin Michael E. , Akshinthala S. Dipikaa , Araki Kiyomi , Rosenberg Avi Z. , Muthuswamy Lakshmi B. , Martin Bernard , Lehmann Brian D. , Berman Hal K. , Pietenpol Jennifer A. , Cardiff Robert D. , Muthuswamy Senthil K.
Published: March 2014

Scribble (SCRIB) localizes to cell–cell junctions and regulates establishment of epithelial cell polarity. Loss of expression of SCRIB functions as a tumor suppressor in Drosophila and mammals; conversely, overexpression of SCRIB promotes epithelial differentiation in mammals. Here, we report that SCRIB is frequently amplified, mRNA overexpressed, and protein is mislocalized from cell–cell junctions in human breast cancers. High levels of SCRIB mRNA are associated with poor clinical prognosis, identifying an unexpected role for SCRIB in breast cancer. We find that transgenic mice expressing a SCRIB mutant [Pro 305 to Leu (P305L)] that fails to localize to cell–cell junctions, under the control of the mouse mammary tumor virus long terminal repeat promoter, develop multifocal hyperplasia that progresses to highly pleomorphic and poorly differentiated tumors with basal characteristics. SCRIB interacts with phosphatase and tensin homolog (PTEN) and the expression of P305L, but not wild-type SCRIB, promotes an increase in PTEN levels in the cytosol. Overexpression of P305L, but not wild-type SCRIB, activates the Akt/mTOR/S6K signaling pathway. Human breast tumors overexpressing SCRIB have high levels of S6K but do not harbor mutations in PTEN or PIK3CA, identifying SCRIB amplification as a mechanism of activating PI3K signaling in tumors without mutations in PIK3CA or PTEN. Thus, we demonstrate that high levels of mislocalized SCRIB functions as a neomorph to promote mammary tumorigenesis by affecting subcellular localization of PTEN and activating an Akt/mTOR/S6kinase signaling pathway. Cancer Res; 74(11); 3180–94. ©2014 AACR.
GWAS-Identified Common Variants for Obesity Are Not Associated with the Risk of Developing Colorectal Cancer
Authors: Sainz Juan , Frank Bernd , da Silva Filho Miguel I. , Hoffmeister Michael , Rudolph Anja , Butterbach Katja , Chang-Claude Jenny , Brenner Hermann , Hemminki Kari , Försti Asta
Published: March 2014

Background: Observational studies have consistently associated obesity with colorectal cancer risk. Because both traits are genetically determined and share some metabolic biomarkers, we hypothesized that obesity-related polymorphisms could also influence the risk of developing colorectal cancer.

Methods: We conducted a comprehensive population-based case–control study in 1,792 German colorectal cancer cases and 1,805 controls to explore associations between 28 obesogenic variants identified through genome-wide association studies (GWAS) and colorectal cancer risk. We also evaluated interactions between polymorphisms and body mass index (BMI), type II diabetes (T2D), and gender.

Results: No evidence of association between obesogenic variants and colorectal cancer risk was observed after correction for multiple testing. There was only a remarkable interaction between the LTArs1041981 polymorphism and gender, which modified the risk of colorectal cancer [Pinteraction = 0.002; males: odds ratio (OR), 1.14; 95% confidence intervals (CI), 1.00–1.30 vs. females: OR, 0.83; 95% CI, 0.71–0.97].

Conclusions: Our findings showed that obesogenic variants are not a major pathogenetic risk factor for colorectal cancer.

Impact: This comprehensive population-based case–control study does not provide evidence of a shared genetic component between obesity and colorectal cancer. Cancer Epidemiol Biomarkers Prev; 23(6); 1125–8. ©2014 AACR.
Complete Protection against Aflatoxin B1-Induced Liver Cancer with a Triterpenoid: DNA Adduct Dosimetry, Molecular Signature, and Genotoxicity Threshold
Authors: Johnson Natalie M. , Egner Patricia A. , Baxter Victoria K. , Sporn Michael B. , Wible Ryan S. , Sutter Thomas R. , Groopman John D. , Kensler Thomas W. , Roebuck Bill D.
Published: March 2014

In experimental animals and humans, aflatoxin B1 (AFB1) is a potent hepatic toxin and carcinogen. The synthetic oleanane triterpenoid 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im), a powerful activator of Keap1-Nrf2 signaling, protects against AFB1-induced toxicity and preneoplastic lesion formation (GST-P–positive foci). This study assessed and mechanistically characterized the chemoprotective efficacy of CDDO-Im against AFB1-induced hepatocellular carcinoma (HCC). A lifetime cancer bioassay was undertaken in F344 rats dosed with AFB1 (200 μg/kg rat/day) for four weeks and receiving either vehicle or CDDO-Im (three times weekly), one week before and throughout the exposure period. Weekly, 24-hour urine samples were collected for analysis of AFB1 metabolites. In a subset of rats, livers were analyzed for GST-P foci. The comparative response of a toxicogenomic RNA expression signature for AFB1 was examined. CDDO-Im completely protected (0/20) against AFB1-induced liver cancer compared with a 96% incidence (22/23) observed in the AFB1 group. With CDDO-Im treatment, integrated level of urinary AFB1-N7-guanine was significantly reduced (66%) and aflatoxin-N-acetylcysteine, a detoxication product, was consistently elevated (300%) after the first AFB1 dose. In AFB1-treated rats, the hepatic burden of GST-P–positive foci increased substantially (0%–13.8%) over the four weeks, but was largely absent with CDDO-Im intervention. The toxicogenomic RNA expression signature characteristic of AFB1 was absent in the AFB1 + CDDO-Im–treated rats. The remarkable efficacy of CDDO-Im as an anticarcinogen is established even in the face of a significant aflatoxin adduct burden. Consequently, the absence of cancer requires a concept of a threshold for DNA damage for cancer development. Cancer Prev Res; 7(7); 658–65. ©2014 AACR.
The Protective Effects of Erythropoietin on Rat Glomerular Podocytes in Culture are Modulated by Extracellular Matrix Proteins
Authors: Krtil Jan , Pláteník Jan , Čuřík Nikola , Brima Wunnie , Tesař Vladimír , Zima Tomáš
Published: March 2014

Background/Aims: Podocytes are typically cultured on collagen I; however, collagen I is absent from healthy glomerular basement membranes. Erythropoietin (EPO) is thought to protect podocytes in vivo. Here, we studied how various types of extracellular matrix (ECM) proteins and EPO affect podocytes in culture. Methods: Primary rat podocytes were replated on collagen I, collagen IV, whole ECM extract, laminin, or bare plastic. Cellular adhesion (8 hours after plating), proliferation (5 days, 10 % serum), and resistance to serum deprivation (3 days, 0.5 % serum) were assessed. BrdU incorporation and expression of podocyte-specific markers were employed as measures of cellular proliferation and differentiation, respectively. qPCR was used to verify expression of EPO receptor in cultured podocytes. Results: Cellular adhesion was similar on all ECM proteins and unaffected by EPO. Proliferation was accelerated by laminin and the ECM extract, but the final cell density was similar on all ECM surfaces. Collagen IV supported the serum-deprived cells better than the other ECM proteins. EPO (2-20 ng/ml) improved viability of serum-deprived podocytes on collagen I, collagen IV, and ECM, but not on laminin or bare plastic. The cells expressed mRNA for EPO receptor. Conclusion: The physiological ECM proteins are more supportive of primary podocytic cultures compared with collagen I. The protective effects of EPO during serum deprivation are modulated by the cultivation surface.
PKB/SGK-Resistant GSK-3 Signaling Following Unilateral Ureteral Obstruction
Authors: Voelkl Jakob , Mia Sobuj , Meissner Adrian , Ahmed Mohamed S. , Feger Martina , Elvira Bernat , Walker Britta , Alessi Dario R. , Alesutan Ioana , Lang Florian
Published: March 2014

Background/Aims: Renal tissue fibrosis contributes to the development of end-stage renal disease. Causes for renal tissue fibrosis include obstructive nephropathy. The development of renal fibrosis following unilateral ureteral obstruction (UUO) is blunted in gene-targeted mice lacking functional serum- and glucocorticoid-inducible kinase SGK1. Similar to Akt isoforms, SGK1 phosphorylates and thus inactivates glycogen synthase kinase GSK-3. The present study explored whether PKB/SGK-dependent phoshorylation of GSK-3α/β impacts on pro-fibrotic signaling following UUO. Methods: UUO was induced in mice carrying a PKB/SGK-resistant GSK-3α/β (gsk-3KI) and corresponding wild-type mice (gsk-3WT). Three days after the obstructive injury, expression of fibrosis markers in kidney tissues was analyzed by quantitative RT-PCR and western blotting. Results: GSK-3α and GSK-3β phosphorylation was absent in both, the non-obstructed and the obstructed kidney tissues from gsk-3KI mice but was increased by UUO in kidney tissues from gsk-3WT mice. Expression of α-smooth muscle actin, type I collagen and type III collagen in the non-obstructed kidney tissues was not significantly different between gsk-3KI mice and gsk-3WT mice but was significantly less increased in the obstructed kidney tissues from gsk-3KI mice than from gsk-3WT mice. After UUO treatment, renal β-catenin protein abundance and renal expression of the β-catenin sensitive genes: c-Myc, Dkk1, Twist and Lef1 were again significantly less increased in kidney tissues from gsk-3KI mice than from gsk-3WT mice. Conclusions: PKB/SGK-dependent phosphorylation of glycogen synthase kinase GSK-3 contributes to the pro-fibrotic signaling leading to renal tissue fibrosis in obstructive nephropathy.
Idiopathic Intracranial Hypertension: A Systematic Analysis of Transverse Sinus Stenting
Authors: Teleb Mohamed S. , Cziep Matthew E. , Lazzaro Marc A. , Gheith Ayman , Asif Kaiz , Remler Bernd , Zaidat Osama O.
Published: March 2014

Background: Idiopathic intracranial hypertension (IIH) is a disorder characterized by signs and symptoms of increased intracranial pressure without structural cause seen on conventional imaging. Hallmark treatment after failed medical management has been CSF shunting or optic nerve fenestration with the objective of preserving vision. Recently, there have been multiple case reports and case series on dural sinus stenting for this disorder. Objective: We aim to review all published cases and case series of dural sinus stenting for IIH, with analysis of patients' presenting symptoms, objective findings (CSF pressures, papilledema, pressure gradients across dural sinuses), follow-up of objective findings, and complications. Methods: A Medline search was performed to identify studies meeting prespecified criteria of a case report or case series of patients treated with dural sinus stent placement for IIH. The papers were reviewed and data were extracted. Results: A total of 22 studies were identified, of which 19 studies (including a total of 207 patients) met the criteria and were included in the analysis. Only three major complications related to the procedure were identified. Headaches resolved or improved in 81% of patients. Papilledema improved in 90% of cases (172 of 189 patients). Sinus pressure decreased from an average of 30.3 to 15 mm Hg. Sinus pressure gradient decreased from 18.5 mm Hg (n = 185) to 3.2 mm Hg (n = 172). Stenting had an overall symptom improvement rate of 87%. Conclusion: Although all published case reports and case series are nonrandomized, the low complication and high symptom improvement rate make dural sinus stenting for IIH a potential alternative surgical treatment. Standardized patient selection and randomization trials or registry are warranted.
Changes in Memory before and after Stroke Differ by Age and Sex, but Not by Race
Authors: Wang Qianyi , Mejía-Guevara Iván , Rist Pamela M. , Walter Stefan , Capistrant Benjamin D. , Glymour M. Maria
Published: March 2014

Background: Post-stroke memory impairment is more common among older adults, women and blacks. It is unclear whether post-stroke differences reflect differential effects of stroke per se or differences in prestroke functioning. We compare memory trajectories before and after stroke by age, sex and race. Methods: Health and Retirement Study participants aged ≥50 years (n = 17,341), with no stroke history at baseline, were interviewed biennially up to 10 years for first self- or proxy-reported stroke (n = 1,574). Segmented linear regression models were used to compare annual rates of memory change before and after stroke among 1,169 stroke survivors, 405 stroke decedents and 15,767 stroke-free participants. Effect modification was evaluated with analyses stratified by baseline age (≤70 vs. >70), sex and race (white vs. nonwhite), and using interaction terms between age/sex/race indicators and annual memory change. Results: Older (>70 years) adults experienced a faster memory decline before stroke (-0.19 vs. -0.10 points/year for survivors, -0.24 vs. -0.13 points/year for decedents, p < 0.001 for both interactions), and among stroke survivors, larger memory decrements (-0.64 vs. -0.26 points, p < 0.001) at stroke and faster memory decline (-0.15 vs. -0.07 points/year, p = 0.003) after stroke onset, compared to younger adults. Female stroke survivors experienced a faster prestroke memory decline than male stroke survivors (-0.14 vs. -0.10 points/year, p < 0.001). However, no sex differences were seen for other contrasts. Although whites had higher post-stroke memory scores than nonwhites, race was not associated with rate of memory decline during any period of time; i.e. race did not significantly modify the rate of decline before or after stroke or the immediate effect of stroke on memory. Conclusions: Older age predicted worse memory change before, at and after stroke onset. Sex and race differences in post-stroke memory outcomes might be attributable to prestroke disparities, which may be unrelated to cerebrovascular disease.
Hypothermia Makes Cerebral Resistance Index a Poor Prognostic Tool in Encephalopathic Newborns
Authors: Skranes J.H. , Elstad M. , Thoresen M. , Cowan F.M. , Stiris T. , Fugelseth D.
Published: March 2014

Background: Severe neonatal encephalopathy (NE) of hypoxic-ischaemic origin may cause death or life-long disability. Acute encephalopathy may also affect cerebrovascular control. Pourcelot's cerebrovascular resistance index (RI) ≤0.55 was predictive of poor outcome in normothermic NE infants. Recent studies have questioned its predictive power during therapeutic hypothermia (HT). Objective: To assess the predictive power of RI during HT and after rewarming. Methods: 45 infants with NE treated with HT for 72 h had their RI calculated during early (median 11 h) and late (median 62 h) cooling and after rewarming (median 89 h). Poor outcome was defined as death or abnormalities on day 10 magnetic resonance imaging shown to predict severe neuromotor disability. Results: RI ≤0.55 during cooling did not differentiate between good and poor outcome (late cooling, p = 0.08), but was powerful after rewarming (p = 0.004). RI ≤0.55 predicted true poor outcome in 43% (95% confidence interval (CI): 12, 80) during late cooling and in 100% (95% CI: 31, 100) after rewarming. RI >0.55 predicted good outcome in 86% (95% CI: 69, 95) during late cooling and in 89% (95% CI: 74, 96) after rewarming. Conclusions: Low RI is not predictive of poor outcome during HT in NE infants, but regains the predictive power seen in normothermic infants after rewarming.
Integration of Magnetoencephalography-Generated Functional Brain Maps into Dose Planning during Arteriovenous Malformation Radiosurgery
Authors: Bowden Greg , Niranjan Ajay , Laing Erika , Pathak Sudhir , Flickinger John , Lunsford L. Dade
Published: March 2014

Background: Magnetoencephalography (MEG) can delineate critical regions of the cortex and facilitate conformal stereotactic radiosurgery (SRS) dose planning. Despite the substantial role of Gamma Knife® SRS in arteriovenous malformation (AVM) management, MEG-generated maps of critical regions have never been utilized to improve dose planning. Purpose: To assess the value of integrating functional brain mapping using MEG with dose planning during treatment of brain AVMs with SRS. Methods: This case series encompassed 5 patients with motor region AVMs. Noninvasive eloquent cortex mapping was achieved using a whole-head 306-channel Neuromag® Vectorview MEG System 5-10 days before SRS. On the day of SRS, the functional brain maps were integrated onto the intraoperative dose planning magnetic resonance imaging for Leksell GammaPlan® version 10. The median AVM volume treated was 12.7 cm3, and 18 Gy was the median margin dose. Results: Functional image integration of MEG improved the recognition of critical brain structures adjacent to the AVM. This facilitated anatomical planning designed to reduce the dose to adjacent critical structures while maintaining a therapeutic dose to the AVM target. The 5 patients had no adverse radiation effects during the follow-up. Conclusion: Coregistration of MEG data improves the accuracy and dose sparing needed for optimal planning during Gamma Knife SRS.
Estradiol and Weight Are Covariates of Paracetamol Clearance in Young Women
Authors: Beleyn B. , Vermeersch S. , Kulo A. , Smits A. , Verbesselt R. , de Hoon J.N. , Van Calsteren K. , Allegaert K.
Published: March 2014

Aim: Paracetamol clearance differs between pregnant and non-pregnant women and between women with or without specific oral contraceptives (OCs). However, an association between female sex hormones and paracetamol clearance has never been explored. Methods: In total, 49 women at delivery, 8 female control subjects without OC use, historical data of 14 women taking OCs, and 15 postpartum observations with and without OCs were pooled to explore covariates of paracetamol clearance. All received a single intravenous 2-gram paracetamol dose, and blood samples were collected up to 6 h after dosing. High-performance liquid chromatography was used to quantify paracetamol. The area under the curve to time infinity (AUC0-∞) was determined and clearance (l/h·m2) was calculated by dose/ AUC0-∞. In addition, estradiol and progesterone were quantified by ELISA with electro-chemiluminescence. Results: Median paracetamol clearance at delivery was significantly higher when compared to postpartum or non-pregnant women (11.9 vs. 6.42 and 8.4 l/h·m2, at least p < 0.05), while an association between paracetamol clearance and estradiol was observed (R = 0.494, p < 0.0001). In non-pregnant subjects, there was no impact of OC exposure on paracetamol clearance. Multiple regression revealed a linear association (Radj = 0.41, p < 0.001) between paracetamol clearance and weight (p = 0.0462) and estradiol (p < 0.0001). Conclusion: Estradiol and weight in part explain the variation in paracetamol clearance in young women.
The Effects of Oral L-Carnitine Supplementation on Physical Capacity and Lipid Metabolism in Chronic Hemodialysis Patients
Authors: Kudoh Yasuo , Aoyama Shinya , Torii Takaaki , Chen Qijie , Nagahara Daigo , Sakata Hiromi , Nozawa Akihiko
Published: March 2014

Background: It is well known that the physical activity in chronic hemodialysis patients decreases compared to that in normal subjects. In order to investigate the effects of L-carnitine on physical capacity and lipid metabolism, a cardiopulmonary exercise test using a bicycle ergometer was performed before and after 3 months of oral L-carnitine supplementation under double-blind conditions. Methods and Results: A total of 20 stable outpatients undergoing hemodialysis treatment were randomly divided into 2 groups: controls receiving placebo and patients receiving 900 mg L-carnitine p.o. daily. The levels of free and acyl carnitine increased significantly from 22.9 ± 7.3 to 149.9 ± 51.8 μmol/l and from 16.0 ± 2.8 to 100.3 ± 50.2 μmol/l, respectively, in the L-carnitine group; however, there was no significant change in other plasma lipid profiles. The exercise time was decreased and the heart rate at the anaerobic threshold was increased in the control group 3 months after the study period, but there were no such changes observed in the L-carnitine group. The minute ventilation/CO2 output slope increased significantly from 38.9 ± 7.8 to 43.8 ± 11.8 in the L-carnitine group. It has been speculated that a shift in the energy source occurs from carbohydrate to lipid, in terms of an increase of oxygen demand. Conclusion:L-Carnitine supplementation might have some beneficial effects on the physical capacity of chronic hemodialysis patients due to the improvement of the lipid metabolism in the muscle.
High Penetrance of a Pan-Canina Type rDNA Family in Intersection Rosa Hybrids Suggests Strong Selection of Bivalent Chromosomes in the Section Caninae
Authors: Crhak Khaitova Lucie , Werlemark Gun , Kovarikova Alena , Nybom Hilde , Kovarik Ales
Published: March 2014

All dogroses (Rosa sect. Caninae) are characterized by the peculiar canina meiosis in which genetic material is unevenly distributed between female and male gametes. The pan-canina rDNA family (termed beta) appears to be conserved in all dogroses analyzed so far. Here, we have studied rDNAs in experimental hybrids obtained from open pollination of F1 plants derived from 2 independent intersectional crosses between the pentaploid dogrose species (2n = 5x = 35) Rosa rubiginosa as female parent (producing 4x egg cells due to the unique asymmetrical canina meiosis) and the tetraploid (2n = 4x = 28) garden rose R. hybrida ‘André Brichet' as male parent (producing 2x pollen after normal meiosis). We analyzed the structure of rDNA units by molecular methods [CAPS and extensive sequencing of internal transcribed spacers (ITS)] and determined the number of loci on chromosomes by FISH. FISH showed that R. rubiginosa and ‘André Brichet' harbored 5 and 4 highly heteromorphic rDNA loci, respectively. In the second generation of hybrid lines, we observed a reduced number of loci (4 and 5 instead of the expected 6). In R. rubiginosa and ‘André Brichet', 2-3 major ITS types were found which is consistent with a weak homogenization pressure maintaining high diversity of ITS types in this genus. In contrast to expectation (the null hypothesis of Mendelian inheritance of ITS families), we observed reduced ITS diversity in some individuals of the second generation which might derive from self-fertilization or from a backcross to R. rubiginosa. In these individuals, the pan-canina beta family appeared to be markedly enriched, while the paternal families were lost or diminished in copies. Although the mechanism of biased meiotic transmission of certain rDNA types is currently unknown, we speculate that the bivalent-forming chromosomes carrying the beta rDNA family exhibit extraordinary pairing efficiency and/or are subjected to strong selection in Caninae polyploids.
An EASO Position Statement on Multidisciplinary Obesity Management in Adults
Authors: Yumuk Volkan , Frühbeck Gema , Oppert Jean Michel , Woodward Euan , Toplak Hermann ,   for the Executive Committee of the European Association for the Study of Obesity
Published: March 2014

Obesity has proven to be a gateway to ill health. It has already reached epidemic proportions becoming one of the leading causes of death and disability in Europe and world-wide. Obesity plays a central role in the development of a number of risk factors and chronic diseases like hypertension, dyslipidaemia and type 2 diabetes mellitus inducing cardiovascular morbidity and mortality. Therefore weight management plays a central role in controlling the respective risk factors and their consequences. Obesity is a complex condition of multifactorial origin. Biological but also psychological and social factors interfere to lead to excess body weight and its deleterious outcomes. Obesity management cannot focus any more only on weight (and BMI) reduction. More attention is to be paid to waist circumference (or waist-to-hip ratio, especially in females), the improvement in body composition (measured with body composition tracking systems like BOD POD, dual energy X-ray absorptiometry or bioelectrical impedance analysis) which is focusing on ameliorating or maintaining fat-free mass and decreasing fat mass. Management of co-morbidities, improving quality of life and well-being of obese patients are also included in treatment aims. This statement emphasises the importance of a comprehensive approach to obesity management.
Permanent Leadless Cardiac Pacing
Authors: Reddy Vivek Y. , Knops Reinoud E. , Sperzel Johannes , Miller Marc A. , Petru Jan , Simon Jaroslav , Sediva Lucie , de Groot Joris R. , Tjong Fleur V.Y. , Jacobson Peter , Ostrosff Alan , Dukkipati Srinivas R. , Koruth Jacob S. , Wilde Arthur A.M. , Kautzner Josef , Neuzil Petr
Published: March 2014

Background—

Conventional cardiac pacemakers are associated with several potential short- and long-term complications related to either the transvenous lead or subcutaneous pulse generator. We tested the safety and clinical performance of a novel, completely self-contained leadless cardiac pacemaker.

Methods and Results—

The primary safety end point was freedom from complications at 90 days. Secondary performance end points included implant success rate, implant time, and measures of device performance (pacing/sensing thresholds and rate-responsive performance). The mean age of the patient cohort (n=33) was 77±8 years, and 67% of the patients were male (n=22/33). The most common indication for cardiac pacing was permanent atrial fibrillation with atrioventricular block (n=22, 67%). The implant success rate was 97% (n=32). Five patients (15%) required the use of >1 leadless cardiac pacemaker during the procedure. One patient developed right ventricular perforation and cardiac tamponade during the implant procedure, and eventually died as the result of a stroke. The overall complication-free rate was 94% (31/33). After 3 months of follow-up, the measures of pacing performance (sensing, impedance, and pacing threshold) either improved or were stable within the accepted range.

Conclusions—

In a prospective nonrandomized study, a completely self-contained, single-chamber leadless cardiac pacemaker has shown to be safe and feasible. The absence of a transvenous lead and subcutaneous pulse generator could represent a paradigm shift in cardiac pacing.

Clinical Trial Registration—

URL:
http://clinicaltrials.gov
. Unique identifier: NCT01700244.
Coinhibitory Suppression of T Cell Activation by CD40 Protects Against Obesity and Adipose Tissue Inflammation in Mice
Authors: Wolf Dennis , Jehle Felix , Michel Nathaly Anto , Bukosza Eva Nora , Rivera Jennifer , Chen Yung Chih , Hoppe Natalie , Dufner Bianca , Rodriguez Alexandra Ortiz , Colberg Christian , Nieto Leandro , Rupprecht Benjamin , Wiedemann Ansgar , Schulte Lisa , Peikert Alexander , Bassler Nicole , Lozhkin Andrey , Hergeth Sonja Patricia , Stachon Peter , Hilgendorf Ingo , Willecke Florian , von zur Mühlen Constantin , von Elverfeldt Dominik , Binder Christoph J. , Aichele Peter , Varo Nerea , Febbraio Mark A. , Libby Peter , Bode Christoph , Peter Karlheinz , Zirlik Andreas
Published: March 2014

Background—

Costimulatory cascades such as the CD40L-CD40 dyad enhance immune cell activation and inflammation during atherosclerosis. Here, we tested the hypothesis that CD40 directly modulates traits of the metabolic syndrome in diet-induced obesity in mice.

Methods and Results—

To induce the metabolic syndrome, wild-type or CD40
−/−
mice consumed a high-fat diet for 20 weeks. Unexpectedly, CD40
−/−
mice exhibited increased weight gain, impaired insulin secretion, augmented accumulation of inflammatory cells in adipose tissue, and enhanced proinflammatory gene expression. This proinflammatory and adverse metabolic phenotype could be transplanted into wild-type mice by reconstitution with CD40-deficient lymphocytes, indicating a major role for CD40 in T or B cells in this context. Conversely, therapeutic activation of CD40 signaling by the stimulating antibody FGK45 abolished further weight gain during the study, lowered glucose levels, improved insulin sensitivity, and suppressed adipose tissue inflammation. Mechanistically, CD40 activation decreased the expression of proinflammatory cytokines in T cells but not in B cells or macrophages. Finally, repopulation of lymphocyte-free Rag1
−/−
mice with CD40
−/−
T cells provoked dysmetabolism and inflammation, corroborating a protective role of CD40 on T cells in the metabolic syndrome. Finally, levels of soluble CD40 showed a positive association with obesity in humans, suggesting clinical relevance of our findings.

Conclusions—

We present the surprising finding that CD40 deficiency on T cells aggravates whereas activation of CD40 signaling improves adipose tissue inflammation and its metabolic complications. Therefore, positive modulation of the CD40 pathway might describe a novel therapeutic concept against cardiometabolic disease.