bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole body metabolic effects of prolonged endurance training in combination with erythropoietin treatment in humans: a randomized placebo controlled trial
Authors: Christensen Britt , Nellemann Birgitte , Larsen Mads S. , Thams Line , Sieljacks Peter , Vestergaard Poul F. , Bibby Bo Martin , Vissing Kristian , Stødkilde-Jørgensen Hans , Pedersen Steen B. , Møller Niels , Nielsen Søren , Jessen Niels , Jørgensen Jens Otto L.
Published: August 2013

Erythropoietin (Epo) administration improves aerobic exercise capacity and insulin sensitivity in renal patients and also increases resting energy expenditure (REE). Similar effects are observed in response to endurance training. The aim was to compare the effects of endurance training with erythropoiesis-stimulating agent (ESA) treatment in healthy humans. Thirty-six healthy untrained men were randomized to 10 wk of either: 1) placebo ( n = 9), 2) ESA ( n = 9), 3) endurance training ( n = 10), or 4) ESA and endurance training ( n = 8). In a single-blinded design, ESA/placebo was injected one time weekly. Training consisted of biking for 1 h at 65% of wattmax three times per week. Measurements performed before and after the intervention were as follows: body composition, maximal oxygen uptake, insulin sensitivity, REE, and palmitate turnover. Uncoupling protein 2 (UCP2) mRNA levels were assessed in skeletal muscle. Fat mass decreased after training ( P = 0.003), whereas ESA induced a small but significant increase in intrahepatic fat ( P = 0.025). Serum free fatty acid (FFA) levels and palmitate turnover decreased significantly in response to training, whereas the opposite pattern was found after ESA. REE corrected for lean body mass increased in response to ESA and training, and muscle UCP2 mRNA levels increased after ESA ( P = 0.035). Insulin sensitivity increased only after training ( P = 0.011). In conclusion: 1) insulin sensitivity is not improved after ESA treatment despite improved exercise capacity, 2) the calorigenic effects of ESA may be related to increased UCP2 gene expression in skeletal muscle, and 3) training and ESA exert opposite effects on lipolysis under basal conditions, increased FFA levels and liver fat fraction was observed after ESA treatment.
Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity
Authors: Maloyan Alina , Muralimanoharan Sribalasubashini , Huffman Steven , Cox Laura A. , Nathanielsz Peter W. , Myatt Leslie , Nijland Mark J.
Published: August 2013

Human and animal studies show that suboptimal intrauterine environments lead to fetal programming, predisposing offspring to disease in later life. Maternal obesity has been shown to program offspring for cardiovascular disease (CVD), diabetes, and obesity. MicroRNAs (miRNAs) are small, noncoding RNA molecules that act as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of cardiac development and etiology of cardiac pathology; however, little is known about their role in the fetal cardiac response to maternal obesity. Our aim was to sequence and profile the cardiac miRNAs that are dysregulated in the hearts of baboon fetuses born to high fat/high fructose-diet (HFD) fed mothers for comparison with fetal hearts from mothers eating a regular diet. Eighty miRNAs were differentially expressed. Of those, 55 miRNAs were upregulated and 25 downregulated with HFD. Twenty-two miRNAs were mapped to human; 14 of these miRNAs were previously reported to be dysregulated in experimental or human CVD. We used an Ingenuity Pathway Analysis to integrate miRNA profiling and bioinformatics predictions to determine miRNA-regulated processes and genes potentially involved in fetal programming. We found a correlation between miRNA expression and putative gene targets involved in developmental disorders and CVD. Cellular death, growth, and proliferation were the most affected cellular functions in response to maternal obesity. Thus, the current study reveals significant alterations in cardiac miRNA expression in the fetus of obese baboons. The epigenetic modifications caused by adverse prenatal environment may represent one of the mechanisms underlying fetal programming of CVD.
Gene expression profiling of articular cartilage reveals functional pathways and networks of candidate genes for osteochondrosis in pigs
Authors: Rangkasenee Noppawan , Murani Eduard , Schellander Karl , Cinar Mehmet Ulas , Ponsuksili Siriluck , Wimmers Klaus
Published: August 2013

Osteochondrosis (OC) is a joint disorder that frequently causes leg weakness in growing pigs, resulting in welfare problems and economic losses. We aimed to detect molecular pathways relevant to the emergence of the disease and to identify candidate genes for the liability to the disorder. Therefore, we compared microarray-based expression patterns of articular cartilage with ( n = 11) and without ( n = 11) histologically diagnosed OC lesions obtained from discordant sib-pairs. A total of 1,564 genes were found with different transcript abundance [differentially expressed (DE) genes] at q ≤ 0.05. To further identify candidate genes, we integrated data from quantitative trait loci (QTL) and genome-wide association (GWA) studies with the expression analysis. We detected 317 DE genes within the QTL confidence intervals, of which 26 DE genes also overlapped GWA regions. Ingenuity Pathway Analysis suggests a pathogenic role of immune response, angiogenesis, and synthesis of extracellular matrix pathways for OC. These processes could facilitate the emergence of defects. But they may also promote the degradation of articular cartilage and the worsening of the disease. A functional network was derived that comprised genes with functional and positional clues of their role in bone and cartilage metabolisms and development, including extracellular matrix genes (e.g., LOX, OGN, and ASPN), angiogenesis genes (e.g., ANGPTL4 and PDGFA), and immune response genes (e.g., ICAM1, AZGP1, C1QB, C1QC, PDE4B, and CDA). The study identified molecular processes linked to OC and several genes with positional, genetic-statistical, and functional evidence for their role in the emergence of articular cartilage lesions and the liability to OC.
f(R)in Holographic and Agegraphic Dark Energy Models and the Generalized Uncertainty Principle
Authors: Majumder Barun
Published: August 2013

We studied a unified approach with the holographic, new agegraphic, andf(R)dark energy model to construct the form off(R)which in general is responsible for the curvature driven explanation of the very early inflation along with presently observed late time acceleration. We considered the generalized uncertainty principle in our approach which incorporated the corrections in the entropy-area relation and thereby modified the energy densities for the cosmological dark energy models considered. We found that holographic and new agegraphicf(R)gravity models can behave like phantom or quintessence models in the spatially flat FRW universe. We also found a distinct term in the form off(R)which goes asR3/2due to the consideration of the GUP modified energy densities. Although the presence of this term in the action can be important in explaining the early inflationary scenario, Capozziello et al. recently showed thatf(R)~R3/2leads to an accelerated expansion, that is, a negative value for the deceleration parameterqwhich fits well with SNeIa and WMAP data.
Biochemical Studies on Methylglyoxal-Mediated Glycated Histones: Implications for Presence of Serum Antibodies against the Glycated Histones in Patients with Type 1 Diabetes Mellitus
Authors: Ansari Nadeem A. , Dash Debabrata
Published: August 2013

Reactive carbonyl species (RCS) mainly reacts with lysine and arginine residues of proteins to form advanced glycation end products (AGEs). Histone was glycoxidated with glyoxal and methylglyoxal. It was characterized by polyacrylamide gel electrophoresis and quenching studies involving penicillamine and aminoguanidine as carbonyl scavengers. Further characterization of histone modified with methylglyoxal was done by UV, fluorescence, and IR spectrophotometry. Spectral analysis of the protein clearly demonstrates structural perturbation in the histone by methylglyoxal. Methylglyoxal-induces cross-linking in the protein leading to aggregation. Role of methylglyoxal mediated glycoxidation of histone in type 1 diabetes was also undertaken. Antibodies were detected against glycoxidated histone in sera of type 1 diabetes patients by solid-phase enzyme immunoassay. The findings indicate that as a result of structural perturbation in histone by methylglyoxal, the modified histone may be involved in production of serum antibodies in the diabetes patients.
Surgical Correction of Patellar Luxation in a Rabbit
Authors: Riggs J. , Langley-Hobbs S. J.
Published: August 2013

A two-and-a-half-year-old giant lop-eared rabbit, weighing 5.1 kg, presented with a one-month history of intermittent right hind limb lameness. The limb locked in extension during hopping. On examination, a grade-2 medial patellar luxation of the right hind was diagnosed, with associated stifle joint swelling. Radiographic findings of the right stifle comprised periarticular osteophyte formation consistent with mild degenerative joint disease and joint effusion. Surgical correction involving right trochlear wedge recession sulcoplasty and lateral imbrication was carried out to stabilise the patella in the trochlear groove. The right hind limb lameness resolved, and the patella was stable at a 6-month postoperative examination. One year postoperatively, the right patella was luxating again concurrent with bilateral stifle effusions. Euthanasia was performed twenty months after surgery due to recurrent lameness in the right hind limb.
COMT-Val158Met-Polymorphism Is Not a Risk Factor for Acute Kidney Injury after Cardiac Surgery
Authors: Kornek Matthias , Deutsch Marcus-André , Eichhorn Stefan , Lahm Harald , Wagenpfeil Stefan , Krane Markus , Lange Ruediger , Boehm Johannes
Published: August 2013

Background. Cardiac surgery-associated acute kidney injury (CSA-AKI) depicts a major complication after cardiac surgery using cardiopulmonary bypass (CPB).Objective. CSA-AKI has clearly been linked to increased perioperative morbidity and mortality. Dysregulations of vasomotor tone are assumed to be causal for CSA-AKI. While catechol-O-methyltransferase (COMT) is involved in metabolizing catecholamines, a single-nucleotide polymorphism (SNP) in the COMT gene leads to different enzyme activities according to genotype. Pilot studies found associations between those COMT genotypes and CSA-AKI.Methods. We prospectively included 1741 patients undergoing elective cardiac surgery using cardiopulmonary bypass (CPB). Patients were genotyped for COMT-Val158Met-(G/A) polymorphism (rs4680).Results. Demographic characteristics and procedural data revealed no significant differences between genotypes. No association between COMT genotypes and the RIFLE criteria could be detected. A multiple linear regression analysis for postoperative creatinine increase revealed highly significant associations for aortic cross-clamp time (P<0.001), CPB time (P<0.001), norepinephrine (P<0.001), and age (P<0.001). No associations were found for COMT genotypes or baseline creatinine. With anR2=0.39and a sample size of 1741, the observed power of the regression analysis was >99%.Conclusions. Based on our results, we can rule out an association between the COMT-Val158Met-(G/A) polymorphism and the appearance of CSA-AKI.
Newer Hemostatic Agents Used in the Practice of Dermatologic Surgery
Authors: Henley Jill , Brewer Jerry D.
Published: August 2013

Minor postoperative bleeding is the most common complication of cutaneous surgery. Because of the commonality of this complication, hemostasis is an important concept to address when considering dermatologic procedures. Patients that have a bleeding diathesis, an inherited/acquired coagulopathy, or who are on anticoagulant/antiplatelet medications pose a greater risk for bleeding complications during the postoperative period. Knowledge of these conditions preoperatively is of the utmost importance, allowing for proper preparation and prevention. Also, it is important to be aware of the various hemostatic modalities available, including electrocoagulation, which is among the most effective and widely used techniques. Prompt recognition of hematoma formation and knowledge of postoperative wound care can prevent further complications such as wound dehiscence, infection, or skin-graft necrosis, minimizing poor outcomes.
In VitroandIn VivoInvestigation of the Potential of Amorphous Microporous Silica as a Protein Delivery Vehicle
Authors: Chaudhari Amol , Vanmellaert Lieve , Bauwens Matthias , Vermaelen Peter , Deroose Christophe M. , Naert Ignace , Cardoso Marcio Vivan , Martens Johan A. , Duyck Joke
Published: August 2013

Delivering growth factors (GFs) at bone/implant interface needs to be optimized to achieve faster osseointegration. Amorphous microporous silica (AMS) has a potential to be used as a carrier and delivery platform for GFs. In this work, adsorption (loading) and release (delivery) mechanism of a model protein, bovine serum albumin (BSA), from AMS was investigatedin vitroas well asin vivo. In general, strong BSA adsorption to AMS was observed. The interaction was stronger at lower pH owing to favorable electrostatic interaction.In vitroevaluation of BSA release revealed a peculiar release profile, involving a burst release followed by a 6 h period without appreciable BSA release and a further slower release later. Experimental data supporting this observation are discussed. Apart from understanding protein/biomaterial (BSA/AMS) interaction, determination ofin vivoprotein release is an essential aspect of the evaluation of a protein delivery system. In this regard micropositron emission tomography (μ-PET) was used in an exploratory experiment to determinein vivoBSA release profile from AMS. Results suggest strongerin vivoretention of BSA when adsorbed on AMS. This study highlights the possible use of AMS as a controlled protein delivery platform which may facilitate osseointegration.
Automated Diagnosis of Otitis Media: Vocabulary and Grammar
Authors: Kuruvilla Anupama , Shaikh Nader , Hoberman Alejandro , Kovačević Jelena
Published: August 2013

We propose a novel automated algorithm for classifying diagnostic categories of otitis media: acute otitis media, otitis media with effusion, and no effusion. Acute otitis media represents a bacterial superinfection of the middle ear fluid, while otitis media with effusion represents a sterile effusion that tends to subside spontaneously. Diagnosing children with acute otitis media is difficult, often leading to overprescription of antibiotics as they are beneficial only for children with acute otitis media. This underscores the need for an accurate and automated diagnostic algorithm. To that end, we design a feature set understood by both otoscopists and engineers based on the actual visual cues used by otoscopists; we term this theotitis media vocabulary. We also design a process to combine the vocabulary terms based on the decision process used by otoscopists; we term this theotitis media grammar. The algorithm achieves 89.9% classification accuracy, outperforming both clinicians who did not receive special training and state-of-the-art classifiers.
Intergenerational Differences in Current Contraceptive Use among Married Women in Uganda
Authors: Wablembo Sarah M. , Doctor Henry V.
Published: August 2013

We analyze variations in contraceptive use and age cohort effects of women born from 1957 to 1991 based on the hypothesis that individuals born at different time periods experience different socio-economic circumstances. Differential exposure to socioeconomic circumstances may influence women's attitudes and behavior towards critical life issues such as contraceptive use. We use data from the 2006 Uganda Demographic and Health Survey by limiting the analysis to 5,362 women who were currently married (or cohabiting) at the time of the survey. Logistic regression analyses show a higher likelihood of contraceptive use among older cohorts than younger cohorts. These results call for interventions that target young women to reduce fertility and reproductive health challenges associated with too many or too closely spaced births. Although variations in age cohorts are critical in influencing current contraceptive use, other factors such as wealth status, education level, and place of residence are equally important. Thus, interventions that focused on selected regions (e.g., the North and the West Nile), rural communities, and efforts to increase literacy levels will accelerate uptake of contraception and improve maternal and child health.
Full-Length Genomic Sequence of Subgenotype IIIA Hepatitis A Virus Isolate in Republic of Korea
Authors: Lee Ah-Ra , Lee Sung-Geun , Kang Lae-Hyung , Jheong Weon-Hwa , Paik Soon-Young
Published: August 2013

Hepatitis A virus is known to cause acute hepatitis and has significant implications for public health throughout the world. In the Republic of Korea, the number of patients with hepatitis A virus infection has been increasing rapidly since 2006. In this study, the Kor-HAV-F strain was identified as subgenotype IIIA by RT-PCR, and its identity was confirmed by nucleotide sequencing and alignment analysis. Moreover, detailed phylogenetic analysis indicated that the Kor-HAV-F strain clustered into subgenotype IIIA, including strains isolated in Japan, Norway, and India. The entire amino acid sequence of the VP1 and 2A regions was compared with that of the reference strains isolated in various countries. We found 2 amino acid changes (T168A and L96P, resp.) in the VP1 and 2A regions, which had not been found in any other hepatitis A virus strain. To our knowledge, this study is the first to report the full-length sequence of a hepatitis A virus isolated in the Republic of Korea.
Gut Microbial Flora, Prebiotics, and Probiotics in IBD: Their Current Usage and Utility
Authors: Scaldaferri Franco , Gerardi Viviana , Lopetuso Loris Riccardo , Del Zompo Fabio , Mangiola Francesca , Boškoski Ivo , Bruno Giovanni , Petito Valentina , Laterza Lucrezia , Cammarota Giovanni , Gaetani Eleonora , Sgambato Alessandro , Gasbarrini Antonio
Published: August 2013

Inflammatory bowel diseases are chronic diseases affecting the gastrointestinal tract, whose major forms are represented by Crohn’s disease (CD) and ulcerative colitis (UC). Their etiology is still unclear, although several factors have been identified as major determinants for induction or relapses. Among these, the role of the “forgotten organ”, gut microbiota, has become more appreciated in recent years. The delicate symbiotic relationship between the gut microbiota and the host appears to be lost in IBD. In this perspective, several studies have been conducted to assess the role of prebiotics and probiotics in gut microbiota modulation. This is a minireview aimed to address in an easy format (simple questions-simple answers) some common issues about the theme. An update on the role of selected constituents of gut microbiota in the pathogenesis of IBD is presented together with the analysis of the efficacy of gut microbiota modulation by prebiotics and probiotics administration in the management of IBD.
Dynamic Decision Making and Race Games
Authors: De Shipra , Seale Darryl A.
Published: August 2013

Frequent criticism of dynamic decision making research pertains to the overly complex nature of the decision tasks used in experimentation. To address such concerns, we study dynamic decision making with respect to a simple race game, which has a computable optimal strategy. In this two-player race game, individuals compete to be the first to reach a designated threshold of points. Players alternate rolling a desired quantity of dice. If the number one appears on any of the dice, the player receives no points for his turn; otherwise, the sum of the numbers appearing on the dice is added to the player's score. Results indicate that although players are influenced by the game state when making their decisions, they tend to play too conservatively in comparison to the optimal policy and are influenced by the behavior of their opponents. Improvement in performance was negligible with repeated play. Survey data suggests that this outcome could be due to inadequate time for learning or insufficient player motivation. However, some players approached optimal heuristic strategies, which perform remarkably well.
Numerical Simulation of Luminescent Downshifting in Top Cell of Monolithic Tandem Solar Cells
Authors: Abderrezek Mahfoud , Fathi Mohamed , Djahli Farid , Ayad Mohammed
Published: August 2013

The increase in the conversion efficiency of monolithic tandem solar cells is limited by the short-circuit current density matching between the top and the bottom cells. Generally, the top cell presents the lowest current in the two subcells. In this paper, in order to increase the short-circuit current density in the top cell, we present a theoretical survey of the luminescence downshifting (LDS) approach for the design of monolithic tandem solar cells. The photovoltaic (PV) glass encapsulation material is replaced with a polymer material of polymethyl methacrylate (PMMA) type which is doped with diverse kinds of organic dyes. The performance of the n-p-p+ GaInP structure has been simulated as a function of the organic dyes. Gains achieved for the short-circuit current density and conversion efficiency are, respectively, 13.13% and 13.38%, under AM1.5G illumination spectra.
Production, Characterization and Antioxidant Potential of Protease fromStreptomycessp. MAB18 Using Poultry Wastes
Authors: Manivasagan Panchanathan , Venkatesan Jayachandran , Sivakumar Kannan , Kim Se-Kwon
Published: August 2013

Poultry waste is an abundant renewable source for the recovery of several value-added metabolites with potential industrial applications. This study describes the production of protease on poultry waste, with the subsequent use of the same poultry waste for the extraction of antioxidants. An extracellular protease-producing strain was isolated from Cuddalore coast, India, and identified asStreptomycessp. MAB18. Its protease was purified 17.13-fold with 21.62% yield with a specific activity of 2398.36 U/mg and the molecular weight was estimated as 43 kDa. The enzyme was optimally active at pH 8–10 and temperature 50–60°C and it was most stable up to pH 12 and 6–12% of NaCl concentration. The enzyme activity was reduced when treated with Hg2+, Pb2+, and SDS and stimulated by Fe2+, Mg2+, Triton X-100, DMSO (dimethyl sulfoxide), sodium sulphite, andβ-mercaptoethanol. Furthermore, the antioxidant activities of protease were evaluated usingin vitroantioxidant assays, such as DPPH radical-scavenging activity, O2scavenging activity, NO scavenging activity, Fe2+chelating activity, and reducing power. The enzyme showed important antioxidant potential with an IC50value of78±0.28 mg/mL. Results of the present study indicate that the poultry waste-derived protease may be useful as supplementary protein and antioxidant in the animal feed formulations.
Topical Application of Ketoprofen Improves Gait Disturbance in Rat Models of Acute Inflammation
Authors: Amagai Yosuke , Tanaka Akane , Matsuda Akira , Oida Kumiko , Jung Kyungsook , Nishikawa Sho , Jang Hyosun , Ishizaka Saori , Matsuda Hiroshi
Published: August 2013

Arthritis is a disabling health problem and commonly develops in the late stages of life; the condition is typically accompanied by chronic pain. For the assessment of pain severity and therapeutic effects of analgesic drugs, we recently developed a gait analysis system, which provides an index of pain severity based on walking stride disturbance. Using this system, we evaluated the therapeutic effect of topical nonsteroidal anti-inflammatory drugs (NSAIDs) in rat models of acute inflammation. We found that the gait analysis system is more sensitive than conventional evaluation methods, such as measurement of swelling or analgesia, which indicated the superiority of our system for drug screening. The approach also indicated that ketoprofen is superior to other NSAIDs for providing pain relief because of its higher skin permeability. To the best of our knowledge, this is the first report demonstrating the effectiveness of topical NSAIDs in experimental animal models of acute inflammation.
Nanographite Films for Solid State Electronic Applications
Authors: Lebedev Sergey G.
Published: August 2013

The structure and properties of nanographite films useful for applications in solid state devices are described. The possibility to use low conducting state of nanographite film for detecting radiation in the segmented solid state detectors is considered. Other interesting phenomena include the field effect conductivity switching which can be used in contactless current limiters and circuit breakers, therf-to-dcconversion which can be utilized in microwave and photo detectors, and light emitting subsequent to the conductivity switching with possible application as light sources. The possible underlying gears of the mentioned effects are discussed.
Evaluation of Mucoadhesive Gels with Propolis (EPP-AF) in Preclinical Treatment of Candidiasis Vulvovaginal Infection
Authors: Berretta Andresa Aparecida , de Castro Patrícia Alves , Cavalheiro Amanda Henriques , Fortes Vanessa Silveira , Bom Vinícius Pedro , Nascimento Andresa Piacezzi , Marquele-Oliveira Franciane , Pedrazzi Vinícius , Ramalho Leandra Naira Zambelli , Goldman Gustavo Henrique
Published: August 2013

Vulvovaginal candidiasis is the second cause of vaginal infection in the USA. Clinical treatment ofC. albicansinfections is routinely performed with polyenes and azole derivatives. However, these drugs are responsible for undesirable side effects and toxicity. In addition,C. albicansazole and echinocandin resistance has been described. Propolis is a bee product traditionally used due to its antimicrobial, anti-inflammatory, and other properties. Therefore, the present work aimed to evaluate different propolis presentations in order to evaluate theirin vitroandin vivoefficacy. The methodologies involved antifungal evaluation, chemical analysis, and the effects of the rheological and mucoadhesive properties of propolis based gels. The obtained results demonstrated the fungicide action of propolis extracts against all three morphotypes (yeast, pseudohyphae, and hyphae) studied. The highest level of fungal cytotoxicity was reached at 6–8 hours of propolis cell incubation. Among the based gel formulations developed, the rheological and mucoadhesive results suggest that propolis based carbopol (CP1%) and chitosan gels were the most pseudoplastic ones. CP1% was the most mucoadhesive preparation, and all of them presented low thixotropy. Results ofin vivoefficacy demonstrated that propolis based gels present antifungal action similar to clotrimazole cream, suggesting that future clinical studies should be performed.
Epilepsy, Antiseizure Therapy, and Sleep Cycle Parameters
Authors: Shvarts Vladimir , Chung Steve
Published: August 2013

A reciprocal relationship exists between sleep and epilepsy. The quality of sleep is affected by the presence and frequency of seizures, type of antiepileptic therapy utilized, and coexisting primary sleep disorders. Daytime somnolence is one of the most common adverse effects of antiepileptic therapy, with specific pharmacologic agents exhibiting a unique influence on components of sleep architecture. The newer generation of antiseizure drugs demonstrates improved sleep efficiency, greater stabilization of sleep architecture, prolongation of REM sleep duration, and increased quality of life measures. The emerging field of chronoepileptology explores the relationship between seizures and circadian rhythms, aiming for targeted use of antiseizure therapies to maximize therapeutic effects and minimize the adverse events experienced by the patients.
The Added Value of Water, Sanitation, and Hygiene Interventions to Mass Drug Administration for Reducing the Prevalence of Trachoma: A Systematic Review Examining
Authors: Travers Anyess , Strasser Sheryl , Palmer Stephanie L. , Stauber Christine
Published: August 2013

Trachoma is the leading cause of infectious blindness worldwide. The SAFE strategy, the World Health Organization-recommended method to eliminate blinding trachoma, combines developments in water, sanitation, surgery, and antibiotic treatment. Current literature does not focus on the comprehensive effect these components have on one another. The present systematic review analyzes the added benefit of water, sanitation, and hygiene education interventions to preventive mass drug administration of azithromycin for trachoma. Trials were identified from the PubMed database using a series of search terms. Three studies met the complete criteria for inclusion. Though all studies found a significant change in reduction of active trachoma prevalence, the research is still too limited to suggest the impact of the “F” and “E” components on trachoma prevalence and ultimately its effects on blindness.
Synthesis and Bioevaluation of Thieno[2,3‐d]pyrimidinone Derivatives as Potential Tumor Cell Growth Inhibitors
Authors: Li Huangyong , Chen Changshui , Xu Shengzhen , Cao Xiufang
Published: August 2013

A series of novel cycloalkylthieno[2,3‐d]pyrimidinone derivatives have been conveniently synthesized via three steps including G‐3CR, heterocyclization, and alkylation reactions as a part of our ongoing search for new bioactive molecules. The newly synthesized compounds were evaluated for their potential tumor cell growth inhibitory activity by standard MTT assay. The preliminary results show that compound 6b exhibited better inhibitory activities against HepG2, MCF‐7, and BCG‐823 cell lines compared to the control.
Optimal Design of Signal Controlled Road Networks Using Differential Evolution Optimization Algorithm
Authors: Ceylan Huseyin
Published: August 2013

This study proposes a traffic congestion minimization model in which the traffic signal setting optimization is performed through a combined simulation-optimization model. In this model, the TRANSYT traffic simulation software is combined with Differential Evolution (DE) optimization algorithm, which is based on the natural selection paradigm. In this context, the EQuilibrium Network Design (EQND) problem is formulated as a bilevel programming problem in which the upper level is the minimization of the total network performance index. In the lower level, the traffic assignment problem, which represents the route choice behavior of the road users, is solved using the Path Flow Estimator (PFE) as a stochastic user equilibrium assessment. The solution of the bilevel EQND problem is carried out by the proposed Differential Evolution and TRANSYT with PFE, the so-called DETRANSPFE model, on a well-known signal controlled test network. Performance of the proposed model is compared to that of two previous works where the EQND problem has been solved by Genetic-Algorithms- (GAs-) and Harmony-Search- (HS-) based models. Results show that the DETRANSPFE model outperforms the GA- and HS-based models in terms of the network performance index and the computational time required.
Electrochemical Evaluation of a Recycled Copolymer Coating for Cultural Heritage Conservation Purposes
Authors: Hernández-Escampa Marco , Rodríguez-Acuña Fausto , Millán-Cruz Franco , Rodríguez-Rojas Pilar , Hernández-Gallegos Miguel , Covelo Alba , Menchaca-Campos Carmina , Uruchurtu Jorge
Published: August 2013

Acrylonitrile-butadiene-styrene (ABS) is a well-known discard product from the industry. This copolymer can be dissolved in organic solvents, and thin films can be created by immersion. Two requirements for coatings used for cultural heritage conservation purposes are transparency and reversibility, both fulfilled by ABS films. The aim of this work was to characterize the copolymer and to evaluate the electrochemical properties of ABS coatings applied to copper. Such performance was compared to that of a commercial varnish commonly used in conservation. The results indicate high protection values of the ABS film, generating a potential application for this waste material. The electrochemical techniques included electrochemical noise, impedance spectroscopy, and potentiodynamic polarization.
HBV Induced HCC: Major Risk Factors from Genetic to Molecular Level
Authors: Ayub Ambreen , Ashfaq Usman Ali , Haque Asma
Published: August 2013

Hepatocellular carcinoma (HCC) is a deadly and emerging disease leading to death in Asian countries. High hepatitis B virus (HBV) load and chronic hepatitis B (CHB) infection increase the risk of developing HCC. HBV is a DNA virus that can integrate DNA into host genome thereby increase the yield of transactivator protein HBxAg that may deregulate many pathways involving in metabolism of cells. Several monogenic and polygenic risk factors are also involved in HCC development. This review summarizes the mechanism involved in HCC development and discusses some promising therapies to make HCC curative.
A Case of Possible Neurosarcoidosis Presenting as Intractable Headache and Panhypopituitarism
Authors: Hwang Jin Kyung , Cho Joo Hee , Park So Young , Son Jung Il , Jo Uk , Chin Sang Ouk , Lee Yun Jung , Choi Moon Chan , Rhee Sang Youl , Kim Eui Jong , Chon Suk
Published: August 2013

Sarcoidosis is a chronic multisystemic inflammatory disease of unknown etiology, which is characterized by noncaseating granulomatous inflammation of the involved organs. It is known that neurosarcoidosis involving the nervous system occurs in about 5% of patients with sarcoidosis. However, neurosarcoidosis without systemic involvement is extremely rare. We present a case of suspicious neurosarcoidosis affecting the pituitary gland, which was manifested as chronic uncontrolled headache, panhypopituitarism, central diabetes insipidus, and hypercalcemia. Though the biopsy at the pituitary lesion was not performed due to the high risk of surgical complication, treatment was needed urgently and we started steroid therapy. After steroid therapy, we observed the immediate symptom relief with improved hypercalcemia. According to the follow-up examination, no recurrent symptom was seen, and resolution of the pituitary lesion with improving panhypopituitarism was noted.
Genome Diversification Mechanism of Rodent and Lagomorpha Chemokine Genes
Authors: Shibata Kanako , Nomiyama Hisayuki , Yoshie Osamu , Tanase Sumio
Published: August 2013

Chemokines are a large family of small cytokines that are involved in host defence and body homeostasis through recruitment of cells expressing their receptors. Their genes are known to undergo rapid evolution. Therefore, the number and content of chemokine genes can be quite diverse among the different species, making the orthologous relationships often ambiguous even between closely related species. Given that rodents and rabbit are useful experimental models in medicine and drug development, we have deduced the chemokine genes from the genome sequences of several rodent species and rabbit and compared them with those of human and mouse to determine the orthologous relationships. The interspecies differences should be taken into consideration when experimental results from animal models are extrapolated into humans. The chemokine gene lists and their orthologous relationships presented here will be useful for studies using these animal models. Our analysis also enables us to reconstruct possible gene duplication processes that generated the different sets of chemokine genes in these species.
Cubic Spline Collocation Method for Fractional Differential Equations
Authors: Yang Shui-Ping , Xiao Ai-Guo
Published: August 2013

We discuss the cubic spline collocation method with two parameters for solving the initial value problems (IVPs) of fractional differential equations (FDEs). Some results of the local truncation error, the convergence, and the stability of this method for IVPs of FDEs are obtained. Some numerical examples verify our theoretical results.
The Clinical Profile and Prognosis of Chinese Children with Melamine-Induced Kidney Disease: A Systematic Review and Meta-Analysis
Authors: Wang Pei-Xin , Li Hong-Tian , Zhang Long , Liu Jian-Meng
Published: August 2013

Introduction. Studies have reported inconsistent results regarding clinical feature and the prognosis status of the affected children in China melamine-contamination event. We summarized available literatures by performing a review and meta-analysis.Methods. Statistical pooling was performed using random-effects model; the sources of heterogeneity were explored through subgroup analyses.Results. Twenty-six studies involving 2164 patients with kidney abnormalities were identified; 94.4% of the patients had urinary calculi and 95.8% of the calculi were <10 mm in diameter. Of 2040 patients with known types of treatment, 5.6% underwent surgical treatment. The pooled recovery rates at 1, 3, 6, and 12 months after diagnosis or treatment initiation were 67.1%, 76.3%, 85.4%, and 92.3%, respectively; these pooled rates did not differ between the study subgroups stratified by mean age at diagnosis, mean duration of melamine exposure, types of patients (inpatient/outpatient), and treatment types (specific/nonspecific), except that the 1-month recovery rate for studies involving a specific treatment (71.9%) was higher than that for studies involving non-specific treatment (46.2%).Conclusion. The majority of patients had small calculi and could recover without surgical treatment. Kidney abnormalities remained in about 8% of the patients at 12-month followup, indicating a need for longer-term followup.
Time Course of the Soleus M Response and H Reflex after Lidocaine Tibial Nerve Block in the Rat
Authors: Buffenoir Kévin , Decq Philippe , Pérot Chantal
Published: August 2013

Aims. In spastic subjects, lidocaine is often used to induce a block predictive of the result provided by subsequent surgery. Lidocaine has been demonstrated to inhibit the Hoffmann (H) reflex to a greater extent than the direct motor (M) response induced by electrical stimulation, but the timecourse of these responses has not been investigated. Methods. An animal (rat) model of the effects of lidocaine on M and H responses was therefore developed to assess this time course. M and H responses were recorded in 18 adult rats before and after application of lidocaine to the sciatic nerve. Results. Two to five minutes after lidocaine injection, M responses were markedly reduced (mean reduction of 44%) and H reflexes were completely abolished. Changes were observed more rapidly for the H reflex. The effects of lidocaine then persisted for 100 minutes. The effect of lidocaine was therefore more prolonged on the H reflex than on the M response. Conclusion. This study confirms that lidocaine blocks not only alpha motoneurons but also Ia afferent fibres responsible for the H reflex. The authors describe, for the first time, the detailed time course of the effect of lidocaine on direct or reflex activation of motoneurons in the rat.
Polyorchidism Presenting with Inguinal Hernia and Hypospadias
Authors: Tatlı Duygu , Numanoglu Kemal Varım
Published: August 2013

Polyorchidism is defined as the presence of more than two testes. Triorchidism is the most frequent presentation. This anomaly is extremely rare, and approximately a hundred cases were described in the literature. We report a case of triorchidism presenting with inguinal hernia and penoscrotal hypospadias in a three-year-old male and briefly discuss current management of polyorchidism. Management remains controversial especially if there is no associated abnormality identified. The absence of any concomitant disorder and if testicular tumour can be ruled out by sonography or magnetic resonance imaging, surgical exploration with biopsy could be unnecessary. On the contrary, surgical exploration has the advantage of allowing for fixation of the testes to prevent torsion and determination of testicular outflow tracts and estimating reproductive capacity.
Chemoprevention of Prostate Cancer by d,l-Sulforaphane Is Augmented by Pharmacological Inhibition of Autophagy
Authors: Vyas Avani R. , Hahm Eun-Ryeong , Arlotti Julie A. , Watkins Simon , Stolz Donna Beer , Desai Dhimant , Amin Shantu , Singh Shivendra V.
Published: August 2013

There is a preclinical evidence that the oral administration of d,l-sulforaphane (SFN) can decrease the incidence or burden of early-stage prostate cancer [prostatic intraepithelial neoplasia (PIN)] and well-differentiated cancer (WDC) but not late-stage poorly differentiated cancer (PDC). Because SFN treatment induces cytoprotective autophagy in cultured human prostate cancer cells, the present study tested the hypothesis that chemopreventive efficacy of SFN could be augmented by the pharmacologic inhibition of autophagy using chloroquine (CQ). Incidence of PDC characterized by prostate weight of more than 1 g was significantly lower in the SFN + CQ group than in control (P = 0.004), CQ group (P = 0.026), or SFN group (P = 0.002 by Fisher exact test). Average size of the metastatic lymph node was lower by about 42% in the SFN + CQ group than in control (P = 0.043 by Wilcoxon test). On the other hand, the SFN + CQ combination was not superior to SFN alone with respect to inhibition of incidence or burden of microscopic PIN or WDC. SFN treatment caused in vivo autophagy as evidenced by transmission electron microscopy. Mechanistic studies showed that prevention of prostate cancer and metastasis by the SFN + CQ combination was associated with decreased cell proliferation, increased apoptosis, alterations in protein levels of autophagy regulators Atg5 and phospho-mTOR, and suppression of biochemical features of epithelial–mesenchymal transition. Plasma proteomics identified protein expression signature that may serve as biomarker of SFN + CQ exposure/response. This study offers a novel combination regimen for future clinical investigations for prevention of prostate cancer in humans. Cancer Res; 73(19); 5985–95. ©2013 AACR.
Merkel Polyomavirus-Specific T Cells Fluctuate with Merkel Cell Carcinoma Burden and Express Therapeutically Targetable PD-1 and Tim-3 Exhaustion Markers
Authors: Afanasiev Olga K. , Yelistratova Lola , Miller Natalie , Nagase Kotaro , Paulson Kelly , Iyer Jayasri G. , Ibrani Dafina , Koelle David M. , Nghiem Paul
Published: August 2013

Purpose: The persistent expression of Merkel cell polyomavirus (MCPyV) oncoproteins in Merkel cell carcinoma (MCC) provides a unique opportunity to characterize immune evasion mechanisms in human cancer. We isolated MCPyV-specific T cells and determined their frequency and functional status.

Experimental Design: Multiparameter flow cytometry panels and HLA/peptide tetramers were used to identify and characterize T cells from tumors (n = 7) and blood (n = 18) of patients with MCC and control subjects (n = 10). PD-1 ligand (PD-L1) and CD8 expression within tumors were determined using mRNA profiling (n = 35) and immunohistochemistry (n = 13).

Results: MCPyV-specific CD8 T cells were detected directly ex vivo from the blood samples of 7 out of 11 (64%) patients with MCPyV-positive tumors. In contrast, 0 of 10 control subjects had detectable levels of these cells in their blood (P < 0.01). MCPyV-specific T cells in serial blood specimens increased with MCC disease progression and decreased with effective therapy. MCPyV-specific CD8 T cells and MCC-infiltrating lymphocytes expressed higher levels of therapeutically targetable PD-1 and Tim-3 inhibitory receptors compared with T cells specific to other human viruses (P < 0.01). PD-L1 was present in 9 of 13 (69%) MCCs and its expression was correlated with CD8-lymphocyte infiltration.

Conclusions: MCC-targeting T cells expand with tumor burden and express high levels of immune checkpoint receptors PD-1 and Tim-3. Reversal of these inhibitory pathways is therefore a promising therapeutic approach for this virus-driven cancer. Clin Cancer Res; 19(19); 5351–60. ©2013 AACR.
Sunitinib and SU11652 Inhibit Acid Sphingomyelinase, Destabilize Lysosomes, and Inhibit Multidrug Resistance
Authors: Ellegaard Anne-Marie , Groth-Pedersen Line , Oorschot Viola , Klumperman Judith , Kirkegaard Thomas , Nylandsted Jesper , Jäättelä Marja
Published: August 2013

Defective apoptosis signaling and multidrug resistance are major barriers for successful cancer treatment. To identify drugs capable of targeting treatment-resistant cancer cells, we screened small-molecule kinase inhibitor libraries for compounds that decrease the viability of apoptosis-resistant human MCF7-Bcl-2 breast cancer cells. SU11652, a multitargeting receptor tyrosine kinase inhibitor, emerged as the most potent compound in the screen. In addition to MCF7-Bcl-2 cells, it effectively killed HeLa cervix carcinoma, U-2-OS osteosarcoma, Du145 prostate carcinoma, and WEHI-S fibrosarcoma cells at low micromolar concentration. SU11652 accumulated rapidly in lysosomes and disturbed their pH regulation and ultrastructure, eventually leading to the leakage of lysosomal proteases into the cytosol. Lysosomal destabilization was preceded by an early inhibition of acid sphingomyelinase, a lysosomal lipase that promotes lysosomal membrane stability. Accordingly, Hsp70, which supports cancer cell survival by increasing lysosomal acid sphingomyelinase activity, conferred partial protection against SU11652-induced cytotoxicity. Remarkably, SU11652 killed multidrug-resistant Du145 prostate cancer cells as effectively as the drug-sensitive parental cells, and subtoxic concentrations of SU11652 effectively inhibited multidrug-resistant phenotype in Du145 prostate cancer cells. Notably, sunitinib, a structurally almost identical and widely used antiangiogenic cancer drug, exhibited similar lysosome-dependent cytotoxic activity, albeit with significantly lower efficacy. The significantly stronger lysosome-targeting activity of SU11652 suggests that it may display better efficacy in cancer treatment than sunitinib, encouraging further evaluation of its anticancer activity in vivo. Furthermore, our data provide a rationale for novel approaches to target drug-resistant cancers by combining classic chemotherapy with sunitinib or SU11652. Mol Cancer Ther; 12(10); 2018–30. ©2013 AACR.
Antianginal Therapy Before Percutaneous Coronary Intervention
Authors: Borden William B. , Spertus John A. , Mushlin Alvin I. , Roe Matthew T. , McCoy Lisa A. , Redberg Rita F.
Published: August 2013

Background—

The regional variability of percutaneous coronary intervention (PCI) rates may be explained by variations in the medical treatment of stable coronary artery disease. We sought to determine whether greater regional use of antianginal medications in PCI patients is associated with lower regional rates of PCI.

Methods and Results—

Using CathPCI Registry and Dartmouth Atlas data, we examined patients undergoing elective PCI for stable coronary artery disease from January 1, 2009, through March 31, 2011, and calculated rates of providing ≥2 antianginal medicines before PCI. We regressed the hospital referral region rates of PCI per 1000 Medicare enrollees in 2007 on the regions’ rates of providing ≥2 antianginal medications before PCI. Among 300 772 PCI procedures, 32.8%, 48.3%, 16.1%, and 2.8% of patients were on 0, 1, 2, or ≥3 antianginal medications, respectively. The median rate of providing ≥2 antianginal medications before PCI was 18.9%. Although substantial variability existed across hospital referral regions in providing ≥2 antianginal medications and in rates of PCI from the Dartmouth Atlas, there was no association between the rates of PCI in each hospital referral region and the rates of ≥2 antianginal medications before PCI (Spearman ρ, 0.0277;
P
=0.64).

Conclusions—

We found no association between the intensity of antianginal therapy and the use of PCI across hospital referral regions, despite the variability of both. Opportunities likely exist in many regions to increase the use of antianginal therapy before proceeding to elective PCI, and more research is needed to explain observed variations in care.