bluuebunny/crossref_metadata_2025 huggingface dataset:
A CLUSTERING-BASED NICHING FRAMEWORK FOR THE APPROXIMATION OF EQUIVALENT PARETO-SUBSETS
Authors: KRAMER OLIVER , DANIELSIEK HOLGER
Published: October 2011

In many optimization problems in practice, multiple objectives have to be optimized at the same time. Some multi-objective problems are characterized by multiple connected Pareto-sets at different parts in decision space — also called equivalent Pareto-subsets. We assume that the practitioner wants to approximate all Pareto-subsets to be able to choose among various solutions with different characteristics. In this work, we propose a clustering-based niching framework for multi-objective population-based approaches that allows to approximate equivalent Pareto-subsets. Iteratively, the clustering process assigns the population to niches, and the multi-objective optimization process concentrates on each niche independently. Two exemplary hybridizations, rake selection and DBSCAN, as well as SMS-EMOA and kernel density clustering demonstrate that the niching framework allows enough diversity to detect and approximate equivalent Pareto-subsets.
Structural Transition in Supercritical Fluids
Authors: Sedunov Boris I.
Published: October 2011

The extension of the saturation curve Ps(T) on the PT diagram in the supercritical region for a number of monocomponent supercritical fluids by peak values for different thermophysical properties, such as heat capacities Cp and Cv and compressibility has been studied. These peaks signal about some sort of fluid structural transition in the supercritical region. Different methods give similar but progressively diverging curves Pst(T) for this transition. The zone of temperatures and pressures near these curves can be named as the zone of the fluid structural transition. The outstanding properties of supercritical fluids in this zone help to understand the physical sense of the fluid structural transition.
Urine Glycoprotein Profile Reveals Novel Markers for Chronic Kidney Disease
Authors: Vivekanandan-Giri Anuradha , Slocum Jessica L. , Buller Carolyn L. , Basrur Venkatesha , Ju Wenjun , Pop-Busui Rodica , Lubman David M. , Kretzler Matthias , Pennathur Subramaniam
Published: October 2011

Chronic kidney disease (CKD) is a significant public health problem, and progression to end-stage renal disease leads to dramatic increases in morbidity and mortality. The mechanisms underlying progression of disease are poorly defined, and current noninvasive markers incompletely correlate with disease progression. Therefore, there is a great need for discovering novel markers for CKD. We utilized a glycoproteomic profiling approach to test the hypothesis that the urinary glycoproteome profile from subjects with CKD would be distinct from healthy controls. N-linked glycoproteins were isolated and enriched from the urine of healthy controls and subjects with CKD. This strategy identified several differentially expressed proteins in CKD, including a diverse array of proteins with endopeptidase inhibitor activity, protein binding functions, and acute-phase/immune-stress response activity supporting the proposal that inflammation may play a central role in CKD. Additionally, several of these proteins have been previously linked to kidney disease implicating a mechanistic role in disease pathogenesis. Collectively, our observations suggest that the human urinary glycoproteome may serve as a discovery source for novel mechanism-based biomarkers of CKD.
Separation of Normal and Premalignant Cervical Epithelial Cells Using Confocal Light Absorption and Scattering Spectroscopic Microscopy Ex Vivo
Authors: Yang Ling , Liu Wen-Tao , Wu Hao , Wang Cheng , Ping Bo , Shi Da-Ren
Published: October 2011

Confocal light absorption and scattering spectroscopic (CLASS) microscopy can detect changes in biochemicals and the morphology of cells. It is therefore used to detect high‐grade cervical squamous intraepithelial lesion (HSIL) cells in the diagnosis of premalignant cervical lesions. Forty cervical samples from women with abnormal Pap smear test results were collected, and twenty cases were diagnosed as HSIL; the rest were normal or low‐grade cervical squamous intraepithelial lesion (LSIL). The enlarged and condensed nuclei of HSIL cells as viewed under CLASS microscopy were much brighter and bigger than those of non‐HSIL cells. Cytological elastic scattered light data was then collected at wavelengths between 400 and 1000 nm. Between 600 nm to 800 nm, the relative elastic scattered light intensity of HSIL cells was higher than that of the non‐HSIL. Relative intensity peaks occurred at 700 nm and 800 nm. CLASS sensitivity and specificity results for HSIL and non‐HSIL compared to cytology diagnoses were 80% and 90%, respectively. This study demonstrated that CLASS microscopy could effectively detect cervical precancerous lesions. Further study will verify this conclusion before the method is used in clinic for early detection of cervical cancer.
Malignant Rhabdoid Tumor of the Lung in the Young Adult: A Case Report
Authors: Attia Adel , Suleman Moosa , Mosleh Hesham
Published: October 2011

Malignant rhabdoid tumor (MRT) is one of the most aggressive and lethal malignancies in pediatric oncology. Malignant rhabdoid tumor was initially described in 1978 as a rhabdomyosarcomatoid variant of a Wilms tumor because of its occurrence in the kidney and because of the resemblance of its cells to rhabdomyoblasts. The absence of muscular differentiation led Haas and colleagues to coin the term rhabdoid tumor of the kidney in 1981, Haas et al..
Existence of Positive Solutions for Neumann Boundary Value Problem with a Variable Coefficient
Authors: Yan Dongming , Zhang Qiang , Pan Zhigang
Published: October 2011

We consider the existence of positive solutions for the Neumann boundary value problem x′′(t) + m2(t)x(t) = f(t, x(t)) + e(t), t ∈ (0,     1), x′(0) = 0, x′(1) = 0, where m ∈ C([0,1], (0, +∞)), e ∈ C[0,1], and f : [0,1]×(0, +∞)→[0, +∞) is continuous. The theorem obtained is very general and complements previous known results.
A Representation of Nonhomogeneous Quadratic Forms with Application to the Least Squares Solution
Authors: Stępniak Czesław
Published: October 2011

The least squares problem appears, among others, in linear models,
and it refers to inconsistent system of linear equations. A crucial question is
how to reduce the least squares solution in such a system to the usual solution
in a consistent one. Traditionally, this is reached by differential calculus. We
present a purely algebraic approach to this problem based on some identities
for nonhomogeneous quadratic forms.
A Young Man with Bilateral Spontaneous Pneumothorax
Authors: Verhaert Liese Lieve Willemien
Published: October 2011

Case.A 33-year-old male nonsmoker presented with sudden onset of dyspnoea and thoracic pain. Chest radiograph showed a left-sided pneumothorax. Few days later he developed a right-sided pneumothorax. He had a positive family history of pneumothorax. High-resolution computed tomography of the chest showed multiple pulmonary cysts predominantly located in the lower lung regions. We suspected Birt-Hogg-Dubé syndrome (BHD).Conclusion.Birt-Hogg-Dubé syndrome is a rare autosomal dominant inherited genodermatosis and characterised by clinical manifestations including hamartomas of the skin, renal tumors, and pulmonary cysts with spontaneous pneumothorax. BHD is probably underdiagnosed because of the wide variability in its clinical expression. It is important to recognize these patients because of the possibility of developing renal cancer.
The Polytopic‐k‐Step Fibonacci Sequences in Finite Groups
Authors: Deveci Ömür
Published: October 2011

We study the polytopic‐k‐step Fibonacci sequences, the polytopic‐k‐step Fibonacci sequences modulo m, and the polytopic‐k‐step Fibonacci sequences in finite groups. Also, we examine the periods of the polytopic‐k‐step Fibonacci sequences in semidihedral group .
Commutativity of Linear Time‐Varying Differential Systems with Nonzero Initial Conditions: A Review and Some New Extensions
Authors: Koksal Muhammet , Koksal Mehmet Emir
Published: October 2011

Necessary and sufficient conditions for the commutativity of linear time‐varying systems are derived in the case of nonzero initial conditions. It is shown that some commutative class of linear time‐varying systems may not commute with arbitrary initial conditions. In this respect, commutativity of Euler differential systems is investigated. Explicit commutativity conditions for the fifth‐order systems are solved. New results about the effects of commutativity on system sensitivity and disturbance properties are presented, which is very important for network design and industrial applications where many of the systems are composed of subsystems cooperating one after another in a chain. The results are supported by examples treated either analytically or numerically.
Synthesis, Production, and Biotechnological Applications of Exopolysaccharides and Polyhydroxyalkanoates by Archaea
Authors: Poli Annarita , Di Donato Paola , Abbamondi Gennaro Roberto , Nicolaus Barbara
Published: October 2011

Extreme environments, generally characterized by atypical temperatures, pH, pressure, salinity, toxicity, and radiation levels, are inhabited by various microorganisms specifically adapted to these particular conditions, called extremophiles. Among these, the microorganisms belonging to the Archaea domain are of significant biotechnological importance as their biopolymers possess unique properties that offer insights into their biology and evolution. Particular attention has been devoted to two main types of biopolymers produced by such peculiar microorganisms, that is, the extracellular polysaccharides (EPSs), considered as a protection against desiccation and predation, and the endocellular polyhydroxyalkanoates (PHAs) that provide an internal reserve of carbon and energy. Here, we report the composition, biosynthesis, and production of EPSs and PHAs by different archaeal species.
Role of Reactive Oxygen Species in the Neural and Hormonal Regulation of the PNMT Gene in PC12 Cells
Authors: Crispo James A. G. , Ansell Dominique R. , Ubriaco Gino , Tai T. C.
Published: October 2011

The stress hormone, epinephrine, is produced predominantly by adrenal chromaffin cells and its biosynthesis is regulated by the enzyme phenylethanolamine N-methyltransferase (PNMT). Studies have demonstrated that PNMT may be regulated hormonally via the hypothalamic-pituitary-adrenal axis and neurally via the stimulation of the splanchnic nerve. Additionally, hypoxia has been shown to play a key role in the regulation of PNMT. The purpose of this study was to examine the impact of reactive oxygen species (ROS) produced by the hypoxia mimetic agent CoCl2, on the hormonal and neural stimulation of PNMT in an in vitro cell culture model, utilizing the rat pheochromocytoma (PC12) cell line. RT-PCR analyses show inductions of the PNMT intron-retaining and intronless mRNA splice variants by CoCl2(3.0- and 1.76-fold, respectively). Transient transfection assays of cells treated simultaneously with CoCl2and the synthetic glucocorticoid, dexamethasone, show increased promoter activity (18.5-fold), while mRNA levels of both splice variants do not demonstrate synergistic effects. Similar results were observed when investigating the effects of CoCl2-induced ROS on the neural stimulation of PNMT via forskolin. Our findings demonstrate that CoCl2-induced ROS have synergistic effects on hormonal and neural activation of the PNMT promoter.
Treatment of Rheumatoid Arthritis with Marine and Botanical Oils: Influence on Serum Lipids
Authors: Olendzki Barbara C. , Leung Katherine , Van Buskirk Susan , Reed George , Zurier Robert B.
Published: October 2011

The gap in mortality between patients with rheumatoid arthritis (RA) and the general population (1.5–3.0 fold risk) is increasing. This disparity is attributable mainly to cardiovascular disease (CVD), as the CVD risk is comparable to patients with diabetes mellitus. The purpose of this study is to determine whether borage seed oil rich in gamma‐linolenic acid, fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or the combination of both oils are useful treatments for dyslipidemia in patients with RA. We randomized patients into a double blind, 18 month trial. Mixed effects models were used to compare trends over time in serum lipids. No significant differences were observed between the three groups: All three treatment groups exhibited similar meaningful improvement in the lipid profile at 9 and 18 months. When all groups were combined, these treatments significantly reduced total and LDL‐cholesterol and triglycerides, increased HDL‐cholesterol, and improved the atherogenic index. All improvements observed at 9 months persisted at 18 months (P < 0.001 verses baseline). Conclusion. Marine and botanical oils may be useful treatment for rheumatoid arthritis patients who are at increased risk for cardiovascular disease compared to the general population.
Prostate Cancer Severity Associations with Neighborhood Deprivation
Authors: Zeigler-Johnson Charnita M. , Tierney Ann , Rebbeck Timothy R. , Rundle Andrew
Published: October 2011

Background. The goal of this paper was to examine neighborhood deprivation and prostate cancer severity.Methods. We studied African American and Caucasian prostate cancer cases from the Pennsylvania State Cancer Registry. Census tract-level variables and deprivation scores were examined in relation to diagnosis stage, grade, and tumor aggressiveness.Results. We observed associations of low SES with high Gleason score among African Americans residing in neighborhoods with low educational attainment (OR = 1.34, 95% CI = 1.13–1.60), high poverty (OR = 1.39, 95% CI = 1.15–1.67), low car ownership (OR = 1.46, 95% CI = 1.20–1.78), and higher percentage of residents on public assistance (OR = 1.32, 95% = 1.08–1.62). The highest quartile of neighborhood deprivation was also associated with high Gleason score. For both Caucasians and African Americans, the highest quartile of neighborhood deprivation was associated with high Gleason score at diagnosis (OR = 1.34, 95% CI = 1.19–1.52; OR = 1.71, 95% CI = 1.21–2.40, resp.).Conclusion. Using a neighborhood deprivation index, we observed associations between high-grade prostate cancer and neighborhood deprivation in Caucasians and African-Americans.
Efficient Protein Transduction Method Using Cationic Peptides and Lipids
Authors: Yamaguchi Kei , Inoue Mari , Goshima Naoki
Published: October 2011

Cationic peptides termed protein transduction domains (PTDs) have been shown to cross biological membranes efficiently. However, proteins transduced by PTDs become entrapped within the endosomal vesicles and are not delivered into organelles. We have developed a novel protein delivery system to enhance the proton sponge effect, which results in rupture of the endosomes, by using a mixture of Wr‐T transporter peptide and a commercially available cationic lipid reagent. This peptide and cationic lipid reagent mixture efficiently delivers a variety of cargo proteins into living cells by releasing them from the endosomes.
Hsp27-Actin Interaction
Authors: Graceffa Philip
Published: October 2011

Hsp27 oligomer is reported to interact with F-actin as a barbed-end-capping protein. The present study determined the binding strength and stoichiometry of the interaction using fluorescence of probes attached to Hsp27 cysteine-137. The fluorescence of acrylodan attached to Hsp27 increased 4-5-fold upon interaction with F-actin. Titration of the fluorescence with F-actin yielded a weak binding constant (KDapp=5.3 μM) with an actin/Hsp27 stoichiometry between < 1 and 6. This stoichiometry is inconsistent with an F-actin end-capping protein. Pyrene attached to Hsp27 exhibited a large excimer fluorescence, in agreement with the known proximity of the cysteine-137's in the Hsp27 oligomer. Upon interaction with F-actin the pyrene-Hsp27 excimer fluorescence was largely lost, suggesting that Hsp27 interacts with F-actin as a monomer, consistent with the acrylodan-Hsp27 results. EM images of F-actin-Hsp27 demonstrated that Hsp27 is not a strong G-actin sequester. Thus, Hsp27,in vitro, is a weak F-actin side-binding protein.
Elevated Troponin and Jarisch-Herxheimer Reaction in Tick-Borne Relapsing Fever: A Case Report
Authors: Hoekstra Kenneth A. , Kelly Michael T.
Published: October 2011

We describe a patient with fever and borreliosis in the Northwestern Washington State, USA. The patient exhibited a classic Jarisch-Herxheimer reaction of tachycardia, hypotension, and thrombocytopenia following antimicrobial therapy, and she also developed an elevated serum cardiac troponin during therapy.
The Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in the Prognostication, Diagnosis, and Management of Thyroid Carcinoma
Authors: Lang Brian Hung-Hin
Published: October 2011

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) plays an increasingly important role in the prognostication, diagnosis, and management of thyroid carcinoma. For patients diagnosed with primary or persistent/recurrent thyroid carcinoma, a finding of FDG-PET positivity implies a more aggressive tumor biology and a distinct mutational profile, both of which carry prognostic significance. Therefore, FDG-PET positivity may be a useful potential risk factor for preoperative risk stratification in primary thyroid carcinoma. This information may help in the planning of subsequent treatment strategy such as the extent of thyroidectomy, prophylactic central neck dissection, and radioiodine ablation. FDG-PET scan has also been found to be a useful adjunct in characterizing indeterminate thyroid nodules on fine needle aspiration cytology. However, larger-sized prospective studies are required to validate this finding. FDG-PET or FDG-PET/CT scan has become the imaging of choice in patients with a negative whole-body radioiodine scan, but with an abnormally raised thyroglobulin level after total thyroidectomy and radioiodine ablation.
Visible-Light Photodegradation of Dye on Co-Doped Titania Nanotubes Prepared by Hydrothermal Synthesis
Authors: Wang Jung-Pin , Yang Hsi-Chi , Hsieh Chien-Te
Published: October 2011

Highly porous Co-doped TiO2nanotubes synthesized from a hydrothermal treatment were used to photodecompose methylene blue (MB) in liquid phase under visible light irradiation. The anatase-type titania nanotubes were found to have high specific surface areas of about 289–379 m2/g. These tubes were shown to be hollow scrolls with outer diameter of about 10–15 nm and length of several micrometers. UV absorption confirmed that Co doping makes the light absorption of nanotubes shift to visible light region. With increasing the dopant concentration, the optical band gap of nanotubes became narrower, ranging from 2.4 eV to 1.8 eV, determined by Kubelka-Munk plot. The Co-doped nanotubes exhibit not only liquid-phase adsorption ability, but also visible-light-derived photodegradation of MB in aqueous solution. The synergetic effect involves two key factors in affecting the photocatalytic activity of Co-doped titania nanotubes under fluorescent lamp, that is, high porosity and optical band gap. The merit of the present work is to provide an efficient route for preparing Co-doped TiO2nanotubes and to clarifying their adsorption and photocatalytic activity under fluorescent lamp.
Tumor Angiogenesis: Pericytes and Maturation Are Not to Be Ignored
Authors: Fakhrejahani Elham , Toi Masakazu
Published: October 2011

Angiogenesis, an essential component of tumor growth and survival, is regulated by complex interactions between several cell types and soluble mediators. Heterogeneous tumor vasculature originates from the collective effect of the nature of carcinoma and the complexity of the angiogenic network. Although the application of angiogenesis inhibitors in some types of cancers has shown clinical benefits, predictive markers to assess treatment effects have yet to be established. In this review, we focus on tumor vessel maturity as a potential marker for evaluating treatment response.
Antiatherogenic and Anti-Ischemic Properties of Traditional Chinese Medicine Xinkeshu via Endothelial Protecting Function
Authors: Tao Xu , Jing-bo Peng , Wen-tong Zhang , Xin Zhao , Tao-tao Zhang , Shi-jun Yang , Lei Fang , Zhong-mei Zou , Da-yong Cai
Published: October 2011

Including herbal medicine, complementary and alternative medicine (CAM) is popular worldwide. The traditional Chinese medicine xinkeshu has been widely used to treat coronary heart disease in China. This study was designed to investigate the protective effect and probable mechanism of xinkeshu tablet to atherosclerotic myocardial ischemia rabbit. Rabbits were divided into four groups (n=12each) and fed with different diet for 12 weeks: Control (standard diet), Model (high-cholesterol diet), XKS (high-cholesterol diet with 184.8 mg/kg/d xinkeshu), and Atorvastatin (high-cholesterol diet with 5.0 mg/kg/d atorvastatin). Plasma lipoprotein, ECG, endothelium-dependent vessel relaxation, histomorphological study, and expressions of eNOS and VCAM-1 on coronary arteries were assessed. The findings showed that, similar to atorvastatin, xinkeshu presented significant effects on rescuing endothelium-dependent vessel relaxation, inhibiting atherosclerotic progress, preventing myocardial ischemia, and changing eNOS and VCAM-1 expression. However, xinkeshu showed no lipoprotein lowering effect in hypercholesterolemia rabbits. The results of the present study indicated that xinkeshu exerted potent antiatherogenic and anti-ischemic properties on atherosclerotic myocardial ischemia rabbit. An endothelial protecting effect may be involved in the mechanism other than antihyperlipidemic effect.
Global Robust Stability of Switched Interval Neural Networks with Discrete and Distributed Time‐Varying Delays of Neural Type
Authors: Wu Huaiqin , Li Ning , Wang Kewang , Xu Guohua , Guo Qiangqiang
Published: October 2011

By combing the theories of the switched systems and the interval neural networks, the mathematics model of the switched interval neural networks with discrete and distributed time‐varying delays of neural type is presented. A set of the interval parameter uncertainty neural networks with discrete and distributed time‐varying delays of neural type are used as the individual subsystem, and an arbitrary switching rule is assumed to coordinate the switching between these networks. By applying the augmented Lyapunov‐Krasovskii functional approach and linear matrix inequality (LMI) techniques, a delay‐dependent criterion is achieved to ensure to such switched interval neural networks to be globally asymptotically robustly stable in terms of LMIs. The unknown gain matrix is determined by solving this delay‐dependent LMIs. Finally, an illustrative example is given to demonstrate the validity of the theoretical results.
Nonconvective Forces: A Critical and Often Ignored Component in the Echocardiographic Assessment of Transvalvular Pressure Gradients
Authors: Firstenberg Michael S. , Abel Erik E. , Papadimos Thomas J. , Tripathi Ravi S.
Published: October 2011

Echocardiography is routinely used to assess ventricular and valvular function, particularly in patients with known or suspected cardiac disease and who have evidence of hemodynamic compromise. A cornerstone to the use of echocardiographic imaging is not only the qualitative assessment, but also the quantitative Doppler-derived velocity characteristics of intracardiac blood flow. While simplified equations, such as the modified Bernoulli equation, are used to estimate intracardiac pressure gradients based upon Doppler velocity data, these modified equations are based upon assumptions of the varying contributions of the different forces that contribute to blood flow. Unfortunately, the assumptions can result in significant miscalculations in determining a gradient if not completely understood or they are misapplied. We briefly summarize the principles of fluid dynamics that are used clinically with some of the inherent limitations of routine broad application of the simplified Bernoulli equation.
A Comprehensive Evaluation of Standardized Assessment Tools in the Diagnosis of Fibromyalgia and in the Assessment of Fibromyalgia Severity
Authors: Boomershine Chad S.
Published: October 2011

Standard assessments for fibromyalgia (FM) diagnosis and core FM symptom domains are needed for biomarker development and treatment trials. Diagnostic and symptom assessments are reviewed and recommendations are made for standards. Recommendations for existing assessments include the American College of Rheumatology FM classification criteria using the manual tender point Survey for diagnosis, the brief pain inventory average pain visual analogue scale for pain intensity, the function subscale of the revised fibromyalgia impact questionnaire (FIQR) for physical function, the patient global impression of change and FIQR for overall/global improvement, the hospital anxiety and depression scale depression subscale for depression, the multiple ability self-report questionnaire for cognitive dysfunction, the fatigue severity scale for fatigue, the FIQR for multidimensional function/health-related quality of life, the jenkins sleep scale for sleep disturbance, and the fibromyalgia intensity score for tenderness. Forthcoming assessments including the FIQR for diagnosis, NIH PROMIS, and FIBRO Change scales are discussed.
Structural Angle and Power Images Reveal Interrelated Gray and White Matter Abnormalities in Schizophrenia
Authors: Xu Lai , Adali Tülay , Schretlen David , Pearlson Godfrey , Calhoun Vince D.
Published: October 2011

We present a feature extraction method to emphasize the interrelationship between gray and white matter and identify tissue distribution abnormalities in schizophrenia. This approach utilizes novel features called structural phase and magnitude images. The phase image indicates the relative contribution of gray and white matter, and the magnitude image reflects the overall tissue concentration. Three different analyses are applied to the phase and magnitude images obtained from 120 healthy controls and 120 schizophrenia patients. First, a single-subject subtraction analysis is computed for an initial evaluation. Second, we analyze the extracted features using voxel based morphometry (VBM) to detect voxelwise group differences. Third, source based morphometry (SBM) analysis was used to determine abnormalities in structural networks that co-vary in a similar way. Six networks were identified showing significantly lower white-to-gray matter in schizophrenia, including thalamus, right precentral-postcentral, left pre/post-central, parietal, right cuneus-frontal, and left cuneus-frontal sources. Interestingly, some networks look similar to functional patterns, such as sensory-motor and vision. Our findings demonstrate that structural phase and magnitude images can naturally and efficiently summarize the associated relationship between gray and white matter. Our approach has wide applicability for studying tissue distribution differences in the healthy and diseased brain.
Pharmacological Inhibition of Soluble Epoxide Hydrolase Ameliorates Diet-Induced Metabolic Syndrome in Rats
Authors: Iyer Abishek , Kauter Kathleen , Alam Md. Ashraful , Hwang Sung Hee , Morisseau Christophe , Hammock Bruce D. , Brown Lindsay
Published: October 2011

The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment withtrans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndromein vivoincluding glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.
Sense and Nonsense of an Extended Pelvic Lymph Node Dissection in Prostate Cancer
Authors: Van Baelen Anthony , Mottet Nicolas , Spahn Martin , Briganti Alberto , Gontero Paolo , Joniau Steven
Published: October 2011

Lymph node metastases associated with prostate cancer (PCa) has been shown to be a poor prognostic factor. The role of pelvic lymph node dissection (PLND) itself in relation to survival remains unclear, however. A Medline search was conducted to address this issue. The following conclusions were drawn. Only recently, improved survival due to completion of radical prostatectomy (RP) (compared to abandoning RP) in known or presumed lymph-node-positive patients has been shown. Lymph node sampling can only be considered representative if an adequate number of nodes is removed. While several authors have suggested that a therapeutic benefit in patients undergoing RP is not provided by PLND, the reliability of these studies is uncertain. Contrary to this, several studies have indicated the possibility of long-term survival even in the presence of limited lymph node metastases. The role and timing of initiation of adjuvant androgen deprivation therapy (ADT) in patients who have node-positive disease after RP is controversial. Recent studies suggest that delaying ADT may not adversely impact survival.
Telomere Targeting with a New G4 Ligand Enhances Radiation-Induced Killing of Human Glioblastoma Cells
Authors: Merle Patrick , Evrard Bertrand , Petitjean Anne , Lehn Jean-Marie , Teulade-Fichou Marie-Paule , Chautard Emmanuel , De Cian Anne , Guittat Lionel , Tran Phong Lan Thao , Mergny Jean-Louis , Verrelle Pierre , Tchirkov Andreï
Published: October 2011

The aim of this study was to test in vitro the efficacy of TAC, an original G-quadruplex ligand, as a potential radiosensitizing agent for glioblastoma multiforme (GBM). Two human radioresistant telomerase-positive GBM cell lines (SF763 and SF767) were analyzed, with and without TAC treatment, for telomere length, cell proliferation, apoptosis, cell-cycle distribution, gene expression, cytogenetic aberrations, clonogenic survival assay, 53BP1 immunofluorescence staining, and γH2AX phosphorylation. We found that low concentrations of TAC (0.5 and 1 μmol/L) inhibited the proliferation of GBM cells in a concentration-dependent manner after only 1 week of treatment, with minimal effects on cell cycle and apoptosis. TAC treatment had no visible effect on average telomere length but modified expression levels of telomere-related genes (hTERT, TRF1, and TRF2) and induced concentration-dependent DNA damage response and dicentric chromosomes. Survival curves analysis showed that exposure to nontoxic, subapoptotic concentrations of TAC enhanced radiation-induced killing of GBM cells. Analysis of DNA repair after irradiation revealed delayed repair kinetics in GBM cells treated with TAC. Furthermore, the combined treatment (TAC and radiation) significantly increased the frequency of chromosomal aberrations as compared with radiation alone. These findings provide the first evidence that exposure to a G4 ligand radiosensitizes human glioblastoma cells and suggest the prospect of future therapeutic applications. Mol Cancer Ther; 10(10); 1784–95. ©2011 AACR.
Subgenotype and Genetic Variability in the Precore/Core Regions of Hepatitis B Virus in Korean Patients with Chronic Liver Disease
Authors: Lyoo Kwang Soo , Hong Sung Woo , Song Myeong Jun , Hur Wonhee , Choi Jung Eun , Piao Lian-Shu , Jang Jeong Won , Bae Si Hyun , Choi Jong Young , Park Jung Wha , Choi Sang Wook , Yoon Seung Kew
Published: October 2011

Objective: The aim of this study was to determine the prevalence of hepatitis B virus (HBV) subgenotypes, the spectrum of mutations in the precore/core region through phylogenetic analysis, and the relevance of viral characteristics in disease progression in Korean patients. Methods: 133 patients with chronic HBV infection were enrolled. The precore and core region of HBV was amplified and sequenced. Phylogenetic analysis was performed for subgenotyping and the changes of nucleotides and amino acid were compared in liver disease stages. Results: HBV/C2 subgenotype was predominant in chronic HBV carriers (98.5%), followed by HBV/A2 (0.75%) and HBV/C7 (0.75%). The mutations of the precore region were not different between liver disease stages. However, amino acid changes in the cytotoxic T lymphocyte epitope (p < 0.020), CD4+ T cell epitope (p < 0.027), or B cell epitope (p < 0.029) were significantly higher in liver cirrhosis patients than in chronic hepatitis patients, but not in hepatocellular carcinoma patients. Conclusion: HBV/C2 is the most prevalent subgenotype in Korea, and HBV/C7 subgenotype found in the Philippines was first identified in the Korean population. Mutations in immune epitopes within the core gene were significantly associated with disease progression.
Replicative Activity of Hepatitis B Virus Is Negatively Associated with Methylation of Covalently Closed Circular DNA in Advanced Hepatitis B Virus Infection
Authors: Kim Jin-Wook , Lee Sang Hyub , Park Young Soo , Hwang Jin-Hyeok , Jeong Sook-Hyang , Kim Nayoung , Lee Dong Ho
Published: October 2011

Objectives: The aim of this study was to examine the methylation status of intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) and to elucidate the possible relationship between the cccDNA methylation and viral replicative activity in patients with HBV-related liver cirrhosis (HBV-LC). Methods: The methylation status of HBV cccDNA was investigated by bisulfite sequencing in nonneoplastic tissues from 12 patients with HBV-LC who underwent surgical resection for combined hepatocellular carcinoma. Clinical, biochemical and virologic factors were evaluated with respect to the degrees of cccDNA methylation. We also examined the effect of methylation of cccDNA on viral transcription by an in vitro transcription assay. Results: Variable degrees of CpG methylation were present in the HBV cccDNA from patients with HBV-LC. Old age, low serum HBV DNA levels and low virion productivity were significantly associated with elevated cccDNA methylation. Virion productivity of cccDNA was also lower in HepAD38 cells with a higher degree of cccDNA methylation. In vitro transcription assays showed that the transcriptional activity of HBV cccDNA was suppressed by increased methylation of cccDNA. Conclusions: Increased CpG methylation of cccDNA is associated with old age, low serum HBV DNA levels and suppressed replicative activity in HBV-LC.
Numerical Diagnoses of Superinfection in Chronic Hepatitis B Viral Dynamics
Authors: Wang Kaifa , Tan Wenting , Tang Yingzi , Deng Guohong
Published: October 2011

Objectives: Fluctuation profile has been observed in chronic hepatitis B patients who are untreated or interrupt therapy. A mathematical model and its parameters could be used to diagnose the assumption of superinfection of hepatocytes and to understand the causes for the spontaneous fluctuation pattern of HBV DNA loads in chronically infected patients. Methods: We propose a new conceptual model in terms of chemical kinetics, which is based on the assumption that hepatocytes can be superinfected with hepatitis B virus (HBV). Minimizing the sum of squares of the deviations, we fitted the model to the HBV DNA trajectories from clinical data and obtained the model parameters. Results: The model with the fitted parameters can capture the tendency of HBV DNA trajectories. The mean value of the fitted number of virions that enter a single hepatocyte at the beginning stage of an invasion is 2.10 ± 0.18. The dynamics patterns may correlate with the clinical phenotypes of patients and the value of clinical parameters, such as α-fetoprotein, hepatitis B e-antigen, hepatitis B e-antibody, total bilirubin and alanine transaminase. Conclusions: The superinfection scenario is possible in HBV infection and it may induce HBV DNA fluctuation in the host.
Pyrazinamide-Induced Anaphylaxis: Diagnosed by Skin Test and Successful Desensitization
Authors: Bavbek Sevim , Yılmaz İnsu , Aydın Ömür , Ozdemir Seçil Kepil
Published: October 2011

Pyrazinamide (PZA), an antituberculosis drug, may cause hypersensitivity reactions. Here, we report a case of anaphylaxis secondary to a PZA administration for tuberculosis pleuritis. To the best of our knowledge, this is the first reported case of strongly possible IgE-mediated, PZA-induced anaphylaxis proved by skin prick test and oral provocation/desensitization.
Chondroblastoma of the Fourth Lumbar Vertebra Diagnosed by Aspiration Biopsy: Case Report and Review of the Literature
Authors: Hernández Martínez Silvia J. , Campa Núñez Hernán , Ornelas Cortinas Gerardo , Garza Garza Raúl
Published: October 2011

Background: A chondroblastoma is a primary benign bone tumor typically involving the epiphysis of long tubular bones. The occurrence of chondroblastoma in the vertebral column is exceptional. To the best of our knowledge, aspiration biopsy (AB) findings of a lumbar chondroblastoma have only been reported in 1 previous case. Case: A 30-year-old female presented with lower back pain with a duration of 1 month. A CT scan of the 4th lumbar vertebra showed a heterogeneous lytic zone within the body and the right side pedicle surrounded by marginal sclerosis. A CT-fluoroscopy-guided AB was performed and rendered a relatively cellular material with round to oval-shaped cells with a discrete amount of cytoplasm and small nuclei. These cells were distributed in a single-cell manner as well as in groups along with multinucleated osteoclast-like cells. A cytological diagnosis of chondroblastoma was issued. Conclusion: Identification of infrequent benign bone lesions in the vertebral column through AB is a challenge, yet it is of the utmost importance in order to render a correct diagnosis.
Bone Remodeling, Bone Mass and Weight Gain in Patients with Stabilized Schizophrenia in Real-Life Conditions Treated with Long-Acting Injectable Risperidone
Authors: Doknic Mirjana , Maric Nadja P. , Britvic Dubravka , Pekic Sandra , Damjanovic Aleksandar , Miljic Dragana , Stojanovic Marko , Radojicic Zoran , Jasovic Gasic Miroslava , Popovic Vera
Published: October 2011

Background: Prolactin-raising antipsychotics, risperidone (antidopaminergic activity), may be associated with low bone mass. On the other hand, risperidone may cause an increase in body weight thought to be favorable for bone. Objectives: (1) To determine bone remodeling parameters and bone mass in patients with schizophrenia on long-term treatment with long-acting injectable risperidone (LAIR) in naturalistic settings, and (2) to evaluate the change in body weight, metabolic profile and neuroendocrine status in these patients. Design: This was a prospective, cross-sectional study. Patients: Patients included 26 outpatients with controlled schizophrenia in real-life conditions (age 31.3 ± 1.3 years, BMI 28.1 ± 1.0) on long-term maintenance therapy with LAIR for a mean of 18.0 ± 1.6 months (range 6–36) with a mean dose of 38 ± 2 mg. 35 subjects matched for sex, age, BMI and education served as healthy controls. Methods: Serum osteocalcin, C-terminal telopeptide of type I collagen (CTx), vitamin D, leptin, prolactin, sex steroids, and parathyroid hormone were assessed. Indices of insulin sensitivity and resistance were determined following an oral glucose tolerance test (OGTT). Bone mineral density (BMD) was measured by dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN). Results: Mild to moderate hyperprolactinemia (1,000–2,000 mU/l) was associated with asymptomatic hypogonadism. Prolactin values >2,000 mU/l occurred in a few female patients. Hypogonadism leads to a slight increase (upper limit of normal) in bone resorption marker (CTx) in patients with schizophrenia (p = 0.023). As for bone mass, although lower at the spine than in healthy subjects, it did not reach statistical significance (p = 0.094), while at the FN, BMD was not different from healthy subjects. Body weight increased on average 8.7 ± 1.6 kg in more than 50% of patients. Leptin levels adjusted for BMI in females were significantly higher in patients than in healthy female subjects (p = 0.018), while in males there was no difference between the groups (p = 0.833). A high prevalence of low vitamin D levels and more current smokers were found in patients with schizophrenia. As for the metabolic profile during treatment with risperidone, the low Matsuda index of insulin sensitivity (p = 0.039) confirmed insulin resistance in these patients. Conclusion: A potential long-term consequence of asymptomatic hypogonadism due to risperidone-induced hyperprolactinemia might cause a slight rise in bone resorption marker (CTx). On the other hand, by increasing body weight, risperidone could have a protective effect on the bone and thus no change in bone mass was recorded when compared with healthy controls.
Replicative Aging Induces Endothelial to Mesenchymal Transition in Human Aortic Endothelial Cells: Potential Role of Inflammation
Authors: Fleenor Bradley S. , Marshall Kurt D. , Rippe Catarina , Seals Douglas R.
Published: October 2011

Thickening of the intimal layer of arteries characterized by expression of smooth muscle α-actin (SMαA), collagen deposition, and inflammation is an important pathophysiological change with aging assumed to be mediated by smooth muscle cells migrating from the medial layer. We tested the novel hypothesis that these characteristics could also reflect an endothelial-mesenchymal (smooth muscle-like) transition (EnMT). Late (‘old’) compared with early (‘young’) passage (45.0 ± 1.2 vs. 27.1 ± 0.5 population doublings) human aortic endothelial cells demonstrated greater smooth muscle (spindle) morphological changes, expression of SMαA and collagen I, nuclear factor-ĸB activation, and transforming growth factor-β (TGF-β) (all p < 0.05). Based on increases in SMαA, stimulation with the proinflammatory cytokine tumor necrosis factor-α, but not with TGF-β, induced EnMT in early passage cells similar to that observed in late passage cells. Here, we present the first evidence for EnMT induced in a model of endothelial cell aging and provide support for proinflammatory signaling in mediating this phenotypic change.
Prothrombotic Gene Variants and Mortality after Cerebral Ischemia of Arterial Origin
Authors: Pruissen D. Martijn O. , Rosendaal Frits R. , Frijns Catharina J.M. , Kappelle L. Jaap , Vos Hans L. , Algra Ale ,   on behalf of the SMART Study Group
Published: October 2011

Background: Several functional prothrombotic gene variants have been associated with cerebral ischemia and myocardial infarction. We hypothesized that such gene variants may also be associated with mortality after cerebral ischemia of arterial origin because of an increased risk of fatal vascular events. Methods: We performed a case-control study in 316 long-term survivors and 887 patients with recent cerebral ischemia of arterial origin. False discovery rate q values were calculated to account for multiple testing. The mean duration between occurrence of cerebral ischemia and DNA collection was 16.8 years in long-term survivors and 3.2 months in recent patients. Results: Two of 23 variants were associated with mortality: the 95Arg allele of the coagulation factor XIII subunit B (F13B) His95Arg variant (OR, 1.5 for Arg/Arg and His/Arg vs. His/His genotype; 95% CI, 1.1–2.2, q = 0.29) and the 4G allele of the plasminogen activator inhibitor-1 (PAI-1) 4G/5G variant (OR, 1.5 for 4G/4G and 5G/4G vs. 5G/5G genotype; 95% CI, 1.1–2.0, q = 0.29). Both associations disappeared after accounting for multiple testing. Data analysis restricted to recently deceased patients (n = 133) yielded similar results. Conclusions: In this hospital-based study none of 23 prothrombotic gene variants were associated with long-term mortality after cerebral ischemia of arterial origin. Prothrombotic gene variants do not appear to play an important role in long-term mortality after cerebral ischemia.
Fast Approach for Clarification of Chromosomal Aberrations by Using LM-PCR and FT-CGH in Leukaemic Sample
Authors: Dittmann Kathleen , Przybylski Grzegorz Krzysztof , Grabarczyk Piotr , Dölken Gottfried , Gesk Stefan , Siebert Reiner , Schmidt Christian Andreas
Published: October 2011

Chromosomal abnormalities, like deletions, amplifications, inversions or translocations, are recurrent features in haematological malignancies. However, the precise molecular breakpoints are frequently not determined. Here we describe a rapid analysis of genetic imbalances combining fine tiling comparative genomic hybridization (FT-CGH) and ligation-mediated PCR (LM-PCR). We clarified an inv(14)(q11q32) in a case of T cell acute lymphoblastic leukaemia with a breakpoint in the TRA/D in 68% of cells detected by fluorescence in situ hybridization. FT-CGH showed several mono- and biallelic losses within TRA/D. LM-PCR disclosed a TRA/D rearrangement on one allele. The other allele revealed an inv(14)(q11q32), joining TRDD2 at 21,977,000 of 14q11 together with the IGH locus at 105,948,000 and 3′-sequence of TRAC at 22,092,000 joined together with IGHV4–61 at 106,166,000. This sensitive approach can unravel complex chromosomal abnormalities in patient samples with a limited amount of aberrant cells and may lead to better diagnostic and therapeutic options.
Vasospasm in Intracerebral Hemorrhage with Ventricular Involvement: A Prospective Pilot Transcranial Doppler Sonography Study
Authors: Kiphuth Ines C. , Huttner Hagen B. , Breuer Lorenz , Engelhorn Tobias , Schwab Stefan , Köhrmann Martin
Published: October 2011

Background: Cerebral vasospasm (VSP) is a common complication after subarachnoid hemorrhage (SAH), but has rarely been reported after intracerebral hemorrhage (ICH) without subarachnoidal bleeding. The underlying pathophysiological mechanism is mainly mediated by circulating heme products within the cerebrospinal fluid, and thus patients with ICH and ventricular involvement (IVH) may also be in danger of developing VSP. The incidence and role of VSP in IVH, however, have not been systematically studied. Methods: We prospectively enrolled 115 patients with ICH with or without IVH into the study between April 2009 and April 2010. All patients received serial extracranial and transcranial Doppler sonography (TCD) at baseline, on days 3–5 and 7–9 to detect and monitor VSP. In addition, CT scans taken on admission, after 24 h and before discharge were evaluated for the occurrence of delayed cerebral ischemia. Results: Three out of 53 patients (5.7%) with IVH showed a significant elevation of flow velocities over the examined timeframe. One of these patients developed severe VSP resulting in secondary ischemic infarction. None of the ICH patients without IVH showed significantly elevated flow velocities or secondary infarction. Conclusions: Cerebral VSP with secondary infarction may occur in patients with spontaneous IVH, though far less frequently than in SAH; thus, systematic screening of all patients with IVH may not be warranted. However, serial TCD should be considered in patients with secondary clinical worsening or extensive IVH.