bluuebunny/crossref_metadata_2025 huggingface dataset:
The structure and activity of potassium supported on SBA-15 molecular sieve: Density functional theory study
Authors: Liu Bing , Wang Daxi , Wang Zhongxue , Zhao Zhen , Chen Yu , Lan Jie
Published: October 2013

The geometries, vibrational frequencies, electronic properties and reactivity of potassium supported on SBA-15 have been theoretically investigated by the density functional theory (DFT) method. The structural model of the potassium supported on SBA-15 was constructed based on our previous work [Wang ZX, Wang DX, Zhao Z, Chen Y, Lan J, A DFT study of the structural units in SBA-15 mesoporous molecular sieve, Comput. Theor. Chem.963, 403, 2011]. This paper is the extension of our previous work. The most favored location of potassium atom was obtained by the calculation of substitution energy. The calculated vibrational frequencies of K /SBA-15 are in good agreement with the experimental results. By analyzing the properties of electronic structure, we found that the O atom of Si - O (2)- K group acts as the Lewis base center and the K atom acts as the Lewis acid center. The reactivity of K /SBA-15 was investigated by calculating the activation of oxygen molecule. The oxygen molecule can be activated by K /SBA-15 with an energy barrier of 103.2 kJ/mol. In the final state, the activated oxygen atoms become new Lewis acid centers, which are predicted to act as the active sites in the catalytic reactions. This study provides a deep insight into the properties of supported potassium catalysts and offers fundamental information for further research.
AN ASSORTMENT OF NEGATIVELY CURVED ENDS
Authors: BELEGRADEK IGOR
Published: October 2013

Motivated by recent groundbreaking work of Ontaneda, we describe a sizable class of closed manifolds such that the product of each manifold in the class with ℝ admits a complete metric of bounded negative sectional curvature which is an exponentially warped near one end and has finite volume near the other end.
DEGREE DISTANCE OF PRODUCT GRAPHS
Authors: PAULRAJA P. , AGNES V. S.
Published: October 2013

We determine the exact value of the degree distance of the cartesian product and the wreath product of two graphs. Also we apply our results to compute the exact degree distance of hypercube, torus, grid, Hamming graph and fence graph.
THE MINIMUM GUARDING TREE PROBLEM
Authors: DUMITRESCU ADRIAN , MITCHELL JOSEPH S. B. , ŻYLIŃSKI PAWEL
Published: October 2013

Given a set ℒ of non-parallel lines in the plane and a nonempty subset ℒ′ ⊆ ℒ, a guarding tree for ℒ′ is a tree contained in the union of the lines in ℒ such that if a mobile guard (agent) runs on the edges of the tree, all lines in ℒ′ are visited by the guard. Similarly, given a connected arrangement 𝒮 of line segments in the plane and a nonempty subset 𝒮′ ⊆ 𝒮, we define a guarding tree for 𝒮′. The minimum guarding tree problem for a given set of lines or line segments is to find a minimum-length guarding tree for the input set. We provide a simple alternative (to [N. Xu, Complexity of minimum corridor guarding problems, Inf. Process. Lett.112(17–18) (2012) 691–696.]) proof of the problem of finding a guarding tree of minimum length for a set of orthogonal (axis-parallel) line segments in the plane. Then, we present two approximation algorithms with factors 2 and 3.98, respectively, for computing a minimum guarding tree for a subset of a set of n arbitrary non-parallel lines in the plane; their running times are O(n8) and O(n6 log n), respectively. Finally, we show that this problem is NP-hard for lines in 3-space.
An albumin leader sequence coupled with a cleavage site modification enhances the yield of recombinant C-terminal Mullerian Inhibiting Substance
Authors: Pépin D. , Hoang M. , Nicolaou F. , Hendren K. , Benedict L.A. , Al-Moujahed A. , Sosulski A. , Marmalidou A. , Vavvas D. , Donahoe P.K.
Published: October 2013

Mullerian Inhibiting Substance (MIS) has been shown to inhibit ovarian cancer cells both in-vitro and in-vivo. Furthermore, recent evidence suggests that MIS may effectively target a putative ovarian cancer progenitor cell population enriched by a panel of CD44+, CD24+, Ep-CAM+, and E-cadherin- cell surface markers. In order to accommodate clinical testing of MIS in ovarian cancer patients, the production of recombinant human MIS must be optimized to increase yield and purity. Here we show that, compared to wild type, the substitution of the MIS leader sequence to that of human serum albumin, combined with a modification of the endogenous cleavage site from RAQR/S to a furin/kex2 RARR/S consensus site results in high expression, increased C-terminus cleavage and a reduction in unwanted cryptic internal cleavage products when produced in CHO cells. Purified MIS containing these alterations retains its capacity to induce regression of the Mullerian duct in fetal rat embryonic urogenital ridge assays.
Effect of peripherally administered leptin antagonist on whole body metabolism and bone microarchitecture and biomechanical properties in the mouse
Authors: Solomon Gili , Atkins Ayelet , Shahar Ron , Gertler Arieh , Monsonego-Ornan Efrat
Published: October 2013

Leptin's in vivo effect on the rodent skeleton depends on the model used and the mode of administration. Superactive mouse leptin antagonist (SMLA) was produced and then pegylated (PEG) to prolong and enhance its in vivo activity. We blocked leptin signaling by injecting this antagonist peripherally into normal mice at various time points and studied their metabolic and skeletal phenotypes. Subcutaneous PEG-SMLA injections into 4-wk-old female C57BL/6J mice increased weight gain and food consumption significantly after only 1 mo, and the effect lasted for the 3 mo of the experiment, proving its central inhibiting activity. Mice showed a significant increase in serum glucose, cholesterol, triglycerides, insulin, and HOMA-IR throughout the experiment. Quantification of gene expression in “metabolic” tissues also indicated the development of insulin resistance. Bone analyses revealed a significant increase in trabecular and cortical parameters measured in both the lumbar vertebrae and tibiae in PEG-SMLA-treated mice in the 1st and 3rd months as well as a significant increase in tibia biomechanical parameters. Interestingly, 30 days of treatment with the antagonist in older mice (aged 3 and 6 mo) affected body weight and eating behavior, just as they had in the 1-mo-old mice, but had no effect on bone parameters, suggesting that leptin's effect on bones, either directly or through its obesogenic effect, is dependent upon stage of skeletal development. This potent and reversible antagonist enabled us to study leptin's in vivo role in whole body and bone metabolism and holds potential for future therapeutic use in diseases involving leptin signaling.
Cue to action processing in motor cortex populations
Authors: Rao Naveen G. , Donoghue John P.
Published: October 2013

The primary motor cortex (MI) commands motor output after kinematics are planned from goals, thought to occur in a larger premotor network. However, there is a growing body of evidence that MI is involved in processes beyond action generation, and neuronal subpopulations may perform computations related to cue-to-action processing. From multielectrode array recordings in awake behaving Macaca mulatta monkeys, our results suggest that early MI ensemble activity during goal-directed reaches is driven by target information when cues are closely linked in time to action. Single-neuron activity spanned cue presentation to movement, with the earliest responses temporally aligned to cue and the later responses better aligned to arm movements. Population decoding revealed that MI's coding of cue direction evolved temporally, likely going from cue to action generation. We confirmed that a portion of MI activity is related to visual target processing by showing changes in MI activity related to the extinguishing of a continuously pursued visual target. These findings support a view that MI is an integral part of a cue-to-action network for immediate responses to environmental stimuli.
Osteoprotegerin, Soluble Receptor Activator of Nuclear Factor-κB Ligand, and Subclinical Atherosclerosis in Children and Adolescents with Type 1 Diabetes Mellitus
Authors: Lambrinoudaki Irene , Tsouvalas Emmanouil , Vakaki Marina , Kaparos George , Stamatelopoulos Kimon , Augoulea Areti , Pliatsika Paraskevi , Alexandrou Andreas , Creatsa Maria , Karavanaki Kyriaki
Published: October 2013

Aims. To evaluate carotid intima-media thickness (cIMT) and biomarkers of the osteoprotegerin/receptor activator of nuclear factor-κB ligand (OPG/RANKL) system in type 1 diabetes (T1DM) children and adolescents and controls.Subjects and Methods. Fifty six T1DM patients (mean ± SD age: 12.0 ± 2.7 years, diabetes duration: 5.42 ± 2.87 years and HbA1c: 8.0 ± 1.5%) and 28 healthy matched controls, were studied with anthropometric and laboratory measurements, including serum OPG, soluble RANKL (sRANKL) and cIMT.Results. Anthropometric, laboratory, and cIMT measurements were similar between T1DM youngsters and controls. However patients with longer diabetes duration (>/7.0 years) had indicatively higher cIMT (cIMT = 0.49 vs 0.44 mm,P0.072) and triglyceride levels than the rest of the patients (93.7 vs 64.6 mg/dl,P0.025). Both in the total study population (β0.418,P0.027) and among T1DM patients separately (β0.604,P0.013), BMI was the only factor associated with cIMT. BMI was further associated with OPG in both groups (β−0.335,P0.003 andβ−0.356,P0.008 respectively), while sRANKL levels were not associated with any factor.Conclusions. BMI was the strongest independent predictor of cIMT among the whole population, and especially in diabetics, suggesting a possible synergistic effect of diabetes and adiposity on atherosclerotic burden. BMI was overall strongly associated with circulating OPG, but the causes of this association remain unclear.
Self-Similar Solutions of the Compressible Flow in One-Space Dimension
Authors: Li Tailong , Chen Ping , Xie Jian
Published: October 2013

For the isentropic compressible fluids in one-space dimension, we prove that the Navier-Stokes equations with density-dependent viscosity have neither forward nor backward self-similar strong solutions with finite kinetic energy. Moreover, we obtain the same result for the nonisentropic compressible gas flow, that is, for the fluid dynamics of the Navier-Stokes equations coupled with a transport equation of entropy. These results generalize those in Guo and Jiang's work (2006) where the one-dimensional compressible fluids with constant viscosity are considered.
A New GMRES(m) Method for Markov Chains
Authors: Pu Bing-Yuan , Huang Ting-Zhu , Wen Chun
Published: October 2013

This paper presents a class of new accelerated restarted GMRES method for calculating the stationary probability vector of an irreducible Markov chain. We focus on the mechanism of this new hybrid method by showing how to periodically combine the GMRES and vector extrapolation method into a much efficient one for improving the convergence rate in Markov chain problems. Numerical experiments are carried out to demonstrate the efficiency of our new algorithm on several typical Markov chain problems.
Scaling Relations for the Cosmological “Constant” in Five-Dimensional Relativity
Authors: Wesson Paul S. , Overduin James M.
Published: October 2013

When the cosmological “constant” is derived from modern five-dimensional relativity, exact solutions imply that for small systems it scales in proportion to the square of the mass. However, a duality transformation implies that for large systems it scales as the inverse square of the mass.
Molecular and Clinical Characterization ofGiardia duodenalisInfection in Preschool Children from Lisbon, Portugal
Authors: Ferreira Filipa Santana , Bellegarde Machado Sá da Bandeira Rita Alexandre dos Santos Soares de , Sampaio Ferreira Constantino Cláudia Alexandra Cecílio de , da Fonseca Ana Maria Teixeira Duarte Cancela , Gomes Joana da Graça Matias , Rodrigues Rúben Miguel Lopes , Atouguia Jorge Luís Marques da Silva , Centeno-Lima Sónia Chavarria Alves Ferreira
Published: October 2013

Giardia duodenalisis the most prevalent intestinal protozoan infection especially in children. In Portugal scarce data are available relative to this infection in preschoolers. The present study was conducted from April to July 2009 in public preschools in Lisbon enrolling 316 children. Stool examination was performed through microscopy. Molecular analysis was conducted in all positive samples forG. duodenalisin order to determine the assemblage and subassemblage of this parasite. Eight of the preschoolers studied children (2.5%, 8/316) were infected withG. duodenalis. Additionally the brother of one of the infected children was also infected. Genotyping analysis targetingssu-rRNAandβ-giardinloci revealed six infections with assemblage A and 3 with assemblage B. Sub-assemblage determination was possible in four of the samples, with three A2 and one A3. The limited number of cases precluded an association of a determined symptom with an assemblage. The data presented here show the relevance of consideringG. duodenalisanalysis in children with intestinal complaints even in developed countries.
Job-Education Mismatch and Its Impact on the Earnings of Immigrants: Evidence from Recent Arrivals to Canada
Authors: Sharaf Mesbah Fathy
Published: October 2013

Using the most recent Longitudinal Survey of Immigrants to Canada, this paper measures the incidence of job-education mismatch, particularly over-education, examines its determinants, and estimates its impact on the earnings of immigrants. Job-education mismatch is measured using the realized match method, and the corresponding earnings impact is estimated using an over-required-under education technique. Determinants of over-education are examined using a bivariate probit model to account for selectivity into employment. Panel data estimation methods are used to estimate earnings equations and the analysis is stratified by gender. Results show that recent immigrants to Canada have a persistent high incidence and intensity of over-education with a substantial negative impact on their earnings. In particular, two-thirds of recent immigrants to Canada are over-educated with a wage loss of 8%, while an under-educated immigrant loses around 2% on average. Results also show that proficiency in English or French and post-immigration investment in education and training significantly reduce the likelihood of being over-educated. The findings of this study could benefit policies directed to help immigrants integrate in the labour market.
Existence and Modification of Halpern-Mann Iterations for Fixed Point and Generalized Mixed Equilibrium Problems with a Bifunction Defined on the Dual Space
Authors: Phuangphoo Pongrus , Kumam Poom
Published: October 2013

We study and establish the existence of a solution for a generalized mixed equilibrium problem with a bifunction defined on the dual space of a Banach space. Furthermore, we also modify Halpern-Mann iterations for finding a common solution of a generalized mixed equilibrium problem and a fixed point problem. Under suitable conditions of the purposed iterative sequences, the strong convergence theorems are established by using sunny generalized nonexpansive retraction in Banach spaces. Our results extend and improve various results existing in the current literature.
Pharmaceutical Applications of Chemometric Techniques
Authors: Singh Inderbir , Juneja Prateek , Kaur Birender , Kumar Pradeep
Published: October 2013

Chemometrics involves application of various statistical methods for drawing vital information from various manufacturing-related processes. Multiway chemometric models like parallel factor analysis (PARAFAC), Tucker-3, N-partial least square (N-PLS), and bilinear models like principle component regression (PCR) and partial least squares (PLS) have been discussed in the paper. Chemometric approaches can be used to analyze the data obtained from various instruments including near infrared (NIR), attenuated total reflectance Fourier transform infrared (ATR-FTIR), high-performance liquid chromatography (HPLC), and terahertz pulse spectroscopy. The technique has been used in the quality assurance and quality control of pharmaceutical solid dosage forms. Moreover, application of chemometric methods in the evaluation of properties of pharmaceutical powders and tablet parametric tests has also been discussed in the review. It has been suggested as a useful method for the real-time in-process testing and is a valuable process analytical tool.
A Generalization on Some New Types of Hardy-Hilbert’s Integral Inequalities
Authors: Sroysang Banyat
Published: October 2013

Sulaiman presented, in 2008, new kinds of Hardy-Hilbert’s integral inequality in which the weight function is homogeneous. In this paper, we present a generalization on the kinds of Hardy-Hilbert’s integral inequality.
Operator Characterizations and Some Properties ofg-Frames on Hilbert Spaces
Authors: Guo Xunxiang
Published: October 2013

Given theg-orthonormal basis for Hilbert spaceH, we characterize theg-frames, normalized tightg-frames, andg-Riesz bases in terms of theg-preframe operators. Then we consider the transformations ofg-frames, normalized tightg-frames, andg-Riesz bases, which are induced by operators and characterize them in terms of the operators. Finally, we discuss the sums andg-dual frames ofg-frames by applying the results of characterizations.
Asymptotic Almost Periodic Functions with Range in a Topological Vector Space
Authors: Khan Liaqat Ali , Alsulami Saud M.
Published: October 2013

The notion of asymptotic almost periodicity wasfirst introduced by Fréchet in 1941 in the case offinite dimensional range spaces. Later, its extension to the case of Banach range spaces and locally convex range spaces has been considered by several authors. In this paper, we have generalized the concept of asymptotic almost periodicity to the case where the range space is a general topological vector space, not necessarily locally convex. Our results thus widen the scope of applications of asymptotic almost periodicity.
Direct Inhibition of Retinoblastoma Phosphorylation by Nimbolide Causes Cell-Cycle Arrest and Suppresses Glioblastoma Growth
Authors: Karkare Swagata , Chhipa Rishi Raj , Anderson Jane , Liu Xiaona , Henry Heather , Gasilina Anjelika , Nassar Nicholas , Roychoudhury Jayeeta , Clark Jason P , Kumar Ashish , Pauletti Giovanni M. , Ghosh Pradip K. , Dasgupta Biplab
Published: October 2013

Purpose: Classical pharmacology allows the use and development of conventional phytomedicine faster and more economically than conventional drugs. This approach should be tested for their efficacy in terms of complementarity and disease control. The purpose of this study was to determine the molecular mechanisms by which nimbolide, a triterpenoid found in the well-known medicinal plant Azadirachta indica, controls glioblastoma growth.

Experimental Design: Using in vitro signaling, anchorage-independent growth, kinase assays, and xenograft models, we investigated the mechanisms of its growth inhibition in glioblastoma.

Results: We show that nimbolide or an ethanol soluble fraction of A. indica leaves (Azt) that contains nimbolide as the principal cytotoxic agent is highly cytotoxic against glioblastoma multiforme in vitro and in vivo. Azt caused cell-cycle arrest, most prominently at the G1–S stage in glioblastoma multiforme cells expressing EGFRvIII, an oncogene present in about 20% to 25% of glioblastoma multiformes. Azt/nimbolide directly inhibited CDK4/CDK6 kinase activity leading to hypophosphorylation of the retinoblastoma protein, cell-cycle arrest at G1—S, and cell death. Independent of retinoblastoma hypophosphorylation, Azt also significantly reduced proliferative and survival advantage of glioblastoma multiforme cells in vitro and in tumor xenografts by downregulating Bcl2 and blocking growth factor-induced phosphorylation of Akt, extracellular signal-regulated kinase 1/2, and STAT3. These effects were specific because Azt did not affect mTOR or other cell-cycle regulators. In vivo, Azt completely prevented initiation and inhibited progression of glioblastoma multiforme growth.

Conclusions: Our preclinical findings demonstrate nimbolide as a potent anti-glioma agent that blocks cell cycle and inhibits glioma growth in vitro and in vivo. Clin Cancer Res; 20(1); 199–212. ©2013 AACR.
BAY 80-6946 Is a Highly Selective Intravenous PI3K Inhibitor with Potent p110α and p110δ Activities in Tumor Cell Lines and Xenograft Models
Authors: Liu Ningshu , Rowley Bruce R. , Bull Cathy O. , Schneider Claudia , Haegebarth Andrea , Schatz Christoph A. , Fracasso Paul R. , Wilkie Dean P. , Hentemann Martin , Wilhelm Scott M. , Scott William J. , Mumberg Dominik , Ziegelbauer Karl
Published: October 2013

Because of the complexity derived from the existence of various phosphoinositide 3-kinase (PI3K) isoforms and their differential roles in cancers, development of PI3K inhibitors with differential pharmacologic and pharmacokinetic profiles would allow best exploration in different indications, combinations, and dosing regimens. Here, we report BAY 80-6946, a highly selective and potent pan-class I PI3K inhibitor with sub-nanomolar IC50s against PI3Kα and PI3Kδ. BAY 80-6946 exhibited preferential inhibition (about 10-fold) of AKT phosphorylation by PI3Kα compared with PI3Kβ in cells. BAY 80-6946 showed superior antitumor activity (>40-fold) in PIK3CA mutant and/or HER2 overexpression as compared with HER2-negative and wild-type PIK3CA breast cancer cell lines. In addition, BAY 80-6946 revealed potent activity to induce apoptosis in a subset of tumor cells with aberrant activation of PI3K as a single agent. In vivo, single intravenous administration of BAY 80-6946 exhibited higher exposure and prolonged inhibition of pAKT levels in tumors versus plasma. BAY 80-6946 is efficacious in tumors with activated PI3K when dosed either continuously or intermittently. Thus, BAY 80-6946 induced 100% complete tumor regression when dosed as a single agent every second day in rats bearing HER2-amplified and PIK3CA-mutated KPL4 breast tumors. In combination with paclitaxel, weekly dosing of BAY 80-6946 is sufficient to reach sustained response in all animals bearing patient-derived non–small cell lung cancer xenografts, despite a short plasma elimination half-life (1 hour) in mice. Thus, BAY 80-6946 is a promising agent with differential pharmacologic and pharmacokinetic properties for the treatment of PI3K-dependent human tumors. Mol Cancer Ther; 12(11); 2319–30. ©2013 AACR.
Genes with Aberrant Expression in Murine Preneoplastic Intestine Show Epigenetic and Expression Changes in Normal Mucosa of Colon Cancer Patients
Authors: Leclerc Daniel , Lévesque Nancy , Cao Yuanhang , Deng Liyuan , Wu Qing , Powell Jasmine , Sapienza Carmen , Rozen Rima
Published: October 2013

An understanding of early genetic/epigenetic changes in colorectal cancer would aid in diagnosis and prognosis. To identify these changes in human preneoplastic tissue, we first studied our mouse model in which Mthfr+/− BALB/c mice fed folate-deficient diets develop intestinal tumors in contrast to Mthfr+/+ BALB/c mice fed control diets. Transcriptome profiling was performed in normal intestine from mice with low or high tumor susceptibility. We identified 12 upregulated and 51 downregulated genes in tumor-prone mice. Affected pathways included retinoid acid synthesis, lipid and glucose metabolism, apoptosis and inflammation. We compared murine candidates from this microarray analysis, and murine candidates from an earlier strain-based comparison, with a set of human genes that we had identified in previous methylome profiling of normal human colonic mucosa, from colorectal cancer patients and controls. From the extensive list of human methylome candidates, our approach uncovered five orthologous genes that had shown changes in murine expression profiles (PDK4, SPRR1A, SPRR2A, NR1H4, and PYCARD). The human orthologs were assayed by bisulfite-pyrosequencing for methylation at 14 CpGs. All CpGs exhibited significant methylation differences in normal mucosa between colorectal cancer patients and controls; expression differences for these genes were also observed. PYCARD and NR1H4 methylation differences showed promise as markers for presence of polyps in controls. We conclude that common pathways are disturbed in preneoplastic intestine in our animal model and morphologically normal mucosa of patients with colorectal cancer, and present an initial version of a DNA methylation-based signature for human preneoplastic colon. Cancer Prev Res; 6(11); 1171–81. ©2013 AACR.
Exposure to Excess Estradiol or Leptin during Pregnancy Increases Mammary Cancer Risk and Prevents Parity-Induced Protective Genomic Changes in Rats
Authors: de Assis Sonia , Wang Mingyue , Jin Lu , Bouker Kerrie B. , Hilakivi-Clarke Leena A.
Published: October 2013

Using a preclinical model, we investigated whether excess estradiol (E2) or leptin during pregnancy affects maternal mammary tumorigenesis in rats initiated by administering carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) on day 50. Two weeks later, rats were mated, and pregnant dams were treated daily with 10 μg of 17β-estradiol, 15 μg of leptin, or vehicle from gestation day 8 to 19. Tumor development was assessed separately during weeks 1 to 12 and 13 to 22 after DMBA administration, because pregnancy is known to induce a transient increase in breast cancer risk, followed by a persistent reduction. Parous rats developed less (32%) mammary tumors than nulliparous rats (59%, P < 0.001), and the majority (93%) of tumors in the parous rats appeared before week 13 (vs. 41% in nulliparous rats), indicating that pregnancy induced a transient increase in breast cancer risk. Parous rats exposed to leptin (final tumor incidence 65%) or E2 (45%) during pregnancy developed mammary tumors throughout the tumor-monitoring period, similar to nulliparous control rats, and the incidence was significantly higher in both the leptin- and E2-exposed dams after week 12 than in the vehicle-exposed parous dams (P < 0.001). The mammary glands of the exposed parous rats contained significantly more proliferating cells (P < 0.001). In addition, the E2- or leptin-treated parous rats did not exhibit the protective genomic signature induced by pregnancy and seen in the parous control rats. Specifically, these rats exhibited downregulation of genes involved in differentiation and immune functions and upregulation of genes involved in angiogenesis, growth, and epithelial-to-mesenchymal transition. Cancer Prev Res; 6(11); 1194–211. ©2013 AACR.
Anti-TNF Therapy in the Treatment of Psoriasis in a Patient with Acute-on-Chronic Pancreatitis
Authors: Clayton Helena , Flatz Lukas , Vollenweider-Roten Sonia , Schoepfer Alain , Gilliet Michel , Conrad Curdin
Published: October 2013

Background: Psoriasis is accepted as a multisystemic disease with several important systemic manifestations. Thus, underlying comorbidities have to be taken into account in the choice of treatment. Objective: To explore the role of anti-TNF therapy in the treatment of psoriasis in a patient with acute-on-chronic pancreatitis. Methods: Here, we present the case of a 75-year-old patient with severe psoriasis also suffering from chronic alcohol-induced pancreatitis with recurrent acute flares. A recent life-threatening episode of acute pancreatitis and ischemic liver precluded the reintroduction of methotrexate. Cyclosporine was also excluded as it has been reported to induce acute pancreatitis. Thus, an anti-TNF treatment was initiated in close collaboration with a gastroenterologist. Results: A year after starting anti-TNF therapy the patient continues to show complete clinical remission of his psoriasis. No side effects, particularly no bacterial infections, were reported. No relapses of the patient's underlying chronic pancreatitis were observed throughout the entire treatment with regular clinical and laboratory monitoring, suggesting that chronic pancreatitis is not per se a contraindication for anti-TNF therapy. Conclusion: This case study opens the way for further questioning on the role of TNF in the pathogenesis of chronic and acute pancreatitis and the use of anti-TNF therapy in its treatment.
Frozen Section Analysis of Ureteral Margins in Patients Undergoing Radical Cystectomy for Bladder Cancer: Differential Impact of Carcinoma in situ in the Bladder on Reliability and Impact on Tumour Recurrence in the Upper Urinary Tract
Authors: Loeser Andreas , Katzenberger Tiemo , Vergho Daniel C. , Kocot Arkadius , Burger Maximilian , Riedmiller Hubertus
Published: October 2013

Background: Patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) are at risk for upper urinary tract recurrence (UUTR), especially in case of carcinoma in situ (CIS). Data on the impact of CIS in the urinary bladder on ureteral tumour involvement or UUTR are conflicting. We presently evaluate the accuracy of intraoperative frozen section analysis (FSA) of the ureteral margin, the incidence of ureteral tumour involvement and their impact on UUTR in patients undergoing RC for UCB with versus without CIS of the bladder. Material and Methods: Between 2003 and 2007, 243 patients underwent RC in our department. 176 of these for UCB, either without CIS (n = 117, group I) or solitary/concomitant CIS (n = 59, group II). FSA was performed. Patients were followed up for UUTR. Results: Overall, 403 ureteral margins - including re-resections - were analysed (group I, n = 232; group II, n = 171). One patient (0.85%) in group I and 21 patients (35.6%) in group II had tumour involvement of the ureter (p < 0.0001) at the time of RC. The false-negative rate of FSA compared to final histopathology was 0.4% (1/232) for group I and 2.9% (5/171) for group II, respectively. Mean duration of follow-up was 26 months (1-72). In group II, 2 patients (1.1%) had UUTR in the follow-up; both had initially positive and subsequently false-negative FSA. Conclusions: Tumour involvement of the ureter is found significantly more often in solitary or concomitant CIS of the bladder. Intraoperative ureteral FSA is accurate and should be recommended in these patients. Ureteral tumour involvement predisposes to UUTR especially with initial positive margins mandating careful follow-up.
How Triadic Dialogue Allows Transfer of Responsibility in Dyadic Tutoring
Authors: Clarà Marc , Mauri Teresa
Published: October 2013

It has usually been argued that the pattern of interaction commonly known as triadic dialogue is not adequate for the purposes of learning or, especially, for transfer of responsibility. However, this pattern has been pervasively found in educational data that, at the same time, clearly show transfer of responsibility. The aim of this paper is to explore how transfer of responsibility is enabled through triadic dialogue. We propose that there are at least three mechanisms of triadic dialogue that enable and foster transfer of responsibility. We call these mechanisms Repeating Gives, Sharing Gives, and Disputing Gives. The paper describes these mechanisms and analyses both how they work and how they allow transfer of responsibility in triadic dialogue, with help of empirical data consisting of interactions between an experienced teacher and a student teacher on a three-month internship in the same school.
Clinical and Pathological Study of 328 Cases of Actinic Keratosis in Eastern Chinese Patients
Authors: Han Yu-Mei , Chen Lian-Jun , Dou Xia , Yang Qin-Ping
Published: October 2013

Background: Actinic keratosis (AK) is prevalent and has been widely studied in fair-skinned populations. However, this is not the case in eastern countries. AK in Asians has not been so thoroughly investigated. Objectives: To analyse the clinical and pathological features of a relatively large number of cases of AK diagnosed in older Chinese patients. Methods: Case histories of 328 patients with pathologically diagnosed AK were analysed retrospectively. Their demographic, clinical, pathological and treatment data were collected for analysis of associated factors. Results: Lesions were usually distributed on the face, especially the cheeks and temples. The most frequent pathological type was hypertrophic. Only 34% of the cases had been diagnosed correctly as AK before biopsy; many were mistaken for seborrhoeic keratosis. Conclusions: Most patients were elderly females and there was a higher incidence of lesions on the face, and a lower incidence on the extremities and trunk; this finding contrasts with previous investigations in fair-skinned people.
Visual Contrast Sensitivity Deficits in ‘Normal' Visual Field of Patients with Homonymous Visual Field Defects due to Stroke: A Pilot Study
Authors: Clatworthy Philip L. , Warburton Elizabeth A. , Tolhurst David J. , Baron Jean-Claude
Published: October 2013

Background: Homonymous visual field defects (VFD) are common following stroke, and often recover, partially or fully, by unknown mechanisms. In clinical practice, visual field recovered on perimetry is often considered perceptually normal. However, studies have shown contrast sensitivity (CS) deficits in patients with stroke and homonymous VFD. This study investigated the origin of visual CS loss in patients with VFD due to stroke. We hypothesised that CS deficits would be found in visual field areas appearing normal on perimetry, in patients with ischaemic stroke affecting the retrochiasmal visual system, and that the spatiotemporal properties of this CS loss would be consistent with those of ‘blindsight', perhaps suggesting similar underlying mechanisms. Methods: CS measurements were made in 20 healthy participants, and in 7 patients with stroke causing homonymous VFD sparing foveal vision, measured using Humphrey static perimetry (SITA-Fast 24-2 procedure). Importantly, patients with concomitant visuospatial neglect were excluded. CS measurements were made using a modification of the method of increasing contrast, corrected for reaction time. Three spatial stimuli were used, at several spatial frequencies: (1) large sinusoidal gratings; (2) foveal Gabor patches; and (3) Gabor patches presenting in the putatively recovered visual field, near VFD. Stimuli with different temporal profiles were used to selectively stimulate transient and sustained visual channels, to provide insight into mechanisms of visual loss and/or recovery. Analysis of variance (ANOVA) was used in the analysis of the measurements, allowing for correction for age and stimulus eccentricity. Results: ANOVA for sustained grating stimuli showed orientation-selective (horizontal) CS loss (p = 0.025); no such loss was apparent in the central visual field (foveal Gabor stimuli). Localised CS close to VFD was reduced in stroke-affected hemifields compared with unaffected hemifields (p ≤ 0.005), though these areas appeared normal on perimetry. In these areas, CS was relatively preserved for transient compared with sustained stimuli (Wilcoxon signed rank tests). Conclusions: The finding of specific CS deficits in the normal-appearing visual field of patients with homonymous VFD due to stroke suggests that static perimetry provides an inadequate assessment of visual function in these patients, with clear implications for testing of vision in clinical practice. The results are consistent with relative sparing of the transient/magnocellular visual channel. These findings demand further investigation. If confirmed in larger, longitudinal studies, this will have important implications for the mechanisms of recovery, and may provide a target for visual rehabilitation - for example, using repeated detection practice (‘perceptual learning').
Body Concept of Patients with Chronic Pruritus in Relation to Scratch Lesions and Psychic Symptoms
Authors: Stumpf A. , Ständer S. , Phan N.Q. , Tanneberger A. , Heuft G. , Schneider G.
Published: October 2013

Background: There are only a few studies about the body concept of patients with chronic pruritus. We examined the body concept of this group of patients taking into account subgroup-specific differences, limitations of quality of life and the comparison to patients with eating disorders and a healthy control group. Methods: 284 participants with chronic pruritus filled in the Frankfurt Body Concept Scale, the Hospital Anxiety and Depression Scale and the Dermatology Life Quality Index. Statistical analysis was performed using t tests, variance analysis and Pearson's correlations. Results: Patients with chronic pruritus had a more negative body concept than healthy individuals but a less negative concept than patients with eating disorders. Higher levels of depression and anxiety were related to a more negative body image. Conclusion: The body concept of patients with chronic pruritus should be taken into consideration when planning therapy. Whether the body concept changes after successful treatment has to be examined in further studies.
Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity
Authors: Kleinnijenhuis Johanneke , Quintin Jessica , Preijers Frank , Benn Christine Stabell , Joosten Leo A.B. , Jacobs Cor , van Loenhout Joke , Xavier Ramnik J. , Aaby Peter , van der Meer Jos W.M. , van Crevel Reinout , Netea Mihai G.
Published: October 2013

We have recently shown that BCG (Bacillus Calmette-Guérin) vaccination in healthy volunteers induces epigenetic reprogramming of monocytes, leading to increased cytokine production in response to nonrelated pathogens for up to 3 months after vaccination. This phenomenon was named ‘trained immunity'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months postvaccination, but these effects were less pronounced 1 year after vaccination. However, monocytes recovered 1 year after vaccination had an increased expression of pattern recognition receptors such as CD14, Toll-like receptor 4 (TLR4) and mannose receptor, and this correlated with an increase in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses.
Elevated Admission Blood Pressure and Stroke Severity in Acute Ischemic Stroke: The Bergen NORSTROKE Study
Authors: Kvistad Christopher Elnan , Logallo Nicola , Oygarden Halvor , Thomassen Lars , Waje-Andreassen Ulrike , Naess Halvor
Published: October 2013

Background: Transient elevated blood pressure (BP) is frequent in patients presenting with acute ischemic stroke. The pathophysiology of this response is not clear and its effect on clinical outcome has shown contradictory results. Some studies have suggested that BP elevation may represent a protective response to enhance perfusion in ischemic brain tissue. In this study, we aimed to explore the association between elevated admission BP and stroke severity in the acute phase of ischemic stroke. If it is true that elevated BP represents a protective response in acute ischemia, we expected an inverse association between elevated BP and admission stroke severity, and a positive association between elevated BP and complete neurological recovery within 24 h and/or favorable short-term outcome. Methods: Patients with ischemic stroke with hospital admission <6 h after symptom onset were prospectively included in a stroke registry (Bergen NORSTROKE Registry). BP was measured immediately after admission in all patients. Elevated BP was defined as systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg. The National Institutes of Health Stroke Scale (NIHSS) was used to assess stroke severity upon admission. Mild stroke was defined as NIHSS score <8, moderate stroke as NIHSS score 8-14, and severe stroke as NIHSS score ≥15. Complete neurological recovery (CNR) was defined as no persistent ischemic stroke symptoms at 24 h after admission. Favorable short-term outcome was defined as a modified Rankin Scale score of 0 or 1 at day 7. Results: A total of 749 patients with ischemic stroke were included, of which 621 patients (82.9%) presented with elevated BP. Elevated BP was independently associated with mild stroke (odds ratio, OR: 2.12; 95% CI: 1.39-3.24; p < 0.001), whereas lack of elevated BP was independently associated with severe stroke (OR: 0.41; 95% CI: 0.25-0.68; p < 0.001). There was a nonsignificant association between elevated BP and CNR (OR: 2.11; 95% CI: 0.96-4.68; p = 0.063), yet no association between elevated BP and favorable short-term outcome (OR: 0.97; 95% CI: 0.59-1.59; p = 0.906) when adjusted for confounders. Conclusion: Our study showed an inverse association between elevated BP and stroke severity on admission, where elevated BP was associated with mild stroke and lack of elevated BP was associated with severe stroke. This could be explained by a protective effect of elevated BP in the acute phase of ischemic stroke, although the absence of association between elevated BP and favorable outcome argues against this hypothesis.
A Husband and a Wife with Simultaneous Presentation of Glioblastoma Multiforme: A Case Report
Authors: Roviello Giandomenico , Petrioli Roberto , Cerase Alfonso , Marsili Stefania , Miracco Clelia , Rubino Giovanni , Tini Paolo
Published: October 2013

Glioblastoma multiforme (GBM) is the most lethal subtype of glioma, classified as a WHO grade 4 infiltrative glioma. The etiology of GBM remains unknown and risk factors can be identified only in a small minority. We report the synchronous occurrence of GBM in an otherwise unrelated married couple, i.e. a husband and his wife, who developed GBM within an interval of 1 month. No specific causative environmental factors were identified for both patients, and the genetic screens were negative for hereditary syndromes. Family history was negative for tumors, and no other incidence of cancer in either siblings, parents or other children was reported. An analysis of the couple's exposure to nonionizing electromagnetic fields and ionizing radiations revealed values within the normal ranges usually found in homes. Overall, conjugal tumors are rarely reported. However, the case reported herein raises important questions about possible etiologic factors.
European Regulatory Tools for Advanced Therapy Medicinal Products
Authors: Flory Egbert , Reinhardt Jens
Published: October 2013

Increasing scientific knowledge and technical innovations in the areas of cell biology, biotechnology and medicine resulted in the development of promising therapeutic approaches for the prevention and treatment of human diseases. Advanced therapy medicinal products (ATMPs) reflect a complex and innovative class of bio-pharmaceuticals as these products are highly research-driven, characterised by innovative manufacturing processes and heterogeneous with regard to their origin, type and complexity. This class of ATMP integrates gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineering products and are often individualized and patient-specific products. Multiple challenges arise from the nature of ATMPs, which are often developed by micro, small and medium sized enterprises, university and academia, for whom regulatory experiences are limited and regulatory requirements are challenging. Regulatory guidance such as the reflection paper on classification of ATMPs and guidelines highlighting product-specific issues support academic research groups and pharmaceutical companies to foster the development of safe and effective ATMPs. This review provides an overview on the European regulatory aspects of ATMPs and highlights specific regulatory tools such as the ATMP classification procedure, a discussion on the hospital exemption for selected ATMPs as well as borderline issues towards transplants/transfusion products.
Psychiatric Presentation of Frontotemporal Dementia Associated with Inclusion Body Myopathy due to the VCP Mutation (R155H) in a French Family
Authors: Jacquin Agnès , Rouaud Olivier , Soichot Pierre , Bejot Yannick , Dygai-Cochet Inna , Sarazin Marie , Stojkovic Tania , Lemesle-Martin Martine , Giroud Maurice , Moreau Thibault
Published: October 2013

Introduction: Inclusion body myopathy with Paget's disease of the bone and frontotemporal dementia (IBMPFD) is a rare late-onset autosomal dominant disorder due to a mutation of the valosin-containing protein (VCP) gene. Case Report: We report the case of a patient who developed progressive weakness of the limbs in his fifties, until he was confined to a wheelchair. At that time, he developed acute behavioural changes including irritability, severe anxiety and major depression, which led to him being hospitalised in a psychiatric hospital. He also suffered from aphasia and executive function impairment, which helped us to diagnose a behavioural form of frontotemporal dementia (FTD). The diagnosis of IBMPFD due to a mutation in the VCP gene was confirmed by a genetic study of the VCP gene (R155H mutation). Discussion: The clinical diagnosis of IBMPFD is suggested by the presence of at least one of three major manifestations as follows: inclusion body myopathy (mean onset at 42 years of age), Paget's disease of the bone and FTD (mean onset at 55 years of age). It is mostly the behavioural form of FTD (behavioural changes, executive dysfunction and aphasia). One interesting finding in our report is the predominance of the psychiatric symptoms at the beginning of the behavioural changes, which led to the diagnosis of FTD. The diagnosis of IBMPFD was confirmed by the genetic study: the R155H mutation found on exon 5 domain CDC48 is the most frequent of the 18 known mutations in the VCP gene.