bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering actin cytoskeletal function in the contractile vascular smooth muscle cell
Authors: Yamin Rina , Morgan Kathleen G.
Published: June 2012

Abstract  This review focuses on the vascular smooth muscle cells present in the medial layer of the blood vessels wall in the fully differentiated state (dVSMCs). The dVSMC contractile phenotype enables these cells to respond in a highly regulated manner to changes in extracellular stimuli. Through modulation of vascular contractile force and vascular compliance dVSMCs regulate blood pressure and blood flow. The cellular and molecular mechanisms by which vascular smooth muscle contractile functions are regulated are not completely elucidated. Recent studies have documented a critical role for actin polymerization and cytoskeletal dynamics in the regulation of contractile function. Here we will review the current understanding of actin cytoskeletal dynamics and focal adhesion function in dVSMCs in order to better understand actin cytoskeleton connections to the extracellular matrix and the effects of cytoskeletal remodelling on vascular contractility and vascular stiffness in health and disease.
A Three-Dimensional Evacuation Simulation Using Digital Human Models With Precise Kinematic Joints
Authors: Kakizaki Takao , Urii Jiro , Endo Mitsuru
Published: June 2012

Disaster drills are important for minimizing the damage caused by earthquakes, floods, and fires. Therefore, mass-evacuation drills are considered to be an important obligation of schools and workplaces that employ several individuals. Moreover, for the validation of drill effectiveness as well as disaster prevention, the significance of mass-evacuation simulation has increased.In the present paper, a three-dimensional mass-evacuation simulation is first explained. The developed multi-agent-based simulation with a detailed three-dimensional building infrastructure uses a kinematic digital human (KDH) model with precise human joints. Simulation of a mass-evacuation drill by high-school students agrees well with the results of actual drills. In addition, considering the transportation of badly injured persons during disasters, digital human motion sets of patients, and transporters have been developed for critical evacuation simulation. Several examples have revealed the possibility of applying the extended simulation to evacuation from houses and hospitals.
The Mycobiome
Authors: Mueller Kristen L.
Published: June 2012

Mammals contain resident fungal intestinal populations that influence disease susceptibility.
Complement Is Bad for Aging
Authors: Gough Nancy R.
Published: June 2012

Aging-associated increases in complement C1q activate the Wnt pathway and compromise tissue regeneration.
Experimental Central Nervous System Aspergillosis Therapy: Efficacy, Drug Levels and Localization, Immunohistopathology, and Toxicity
Authors: Clemons Karl V. , Schwartz Julie A. , Stevens David A.
Published: June 2012

We have shown previously that high-dose lipid amphotericin preparations are not more efficacious than lower doses in aspergillosis. We studied toxicity, drug concentrations and localization, and quantitative infection concurrently, using a 4-day model of central nervous system (CNS) aspergillosis to assess early events. Mice given
Aspergillus fumigatus
conidia intracerebrally, under a cyclophosphamide immunosuppressive regimen, were treated for 3 days (AmBisome at 3 or 10 mg/kg of body weight, Abelcet at 10 mg/kg, amphotericin B deoxycholate at 1 mg/kg, caspofungin at 5 mg/kg, or voriconazole at 40 mg/kg). Sampling 24 h after the last treatment showed that AmBisome at 3 but not at 10 mg/kg, as well as Abelcet, caspofungin, and voriconazole, reduced brain CFU. All regimens reduced renal infection. Minor renal tubular changes occurred with AmBisome or Abelcet therapy, whereas heart, lung, and brain showed no drug toxicity. Amphotericin B tissue and serum concentrations did not correlate with efficacy. Endothelial cell activation (ICAM-1 and P-selectin in cerebral capillaries) occurred during infection. Amphotericin B derived from AmBisome and Abelcet localized in activated endothelium and from Abelcet in intravascular monocytes. In 10-day studies dosing uninfected mice, minor renal tubular changes occurred after AmBisome or Abelcet at 1, 5, or 10 mg/kg with or without cyclophosphamide treatment; nephrosis occurred only with Abelcet in cyclophosphamide-treated mice. Hepatotoxicity occurred with AmBisome and Abelcet but was reduced in cyclophosphamide-treated mice. Marked CFU reduction by AmBisome at 3 mg/kg occurred in association with relatively more intense inflammation. Abelcet renal localization appears to be a precursor to late nephrotoxicity. Hepatotoxicity may contribute to high-dose Abelcet and AmBisome failures. Our novel observation of endothelial amphotericin localization during infection may contribute to amphotericin mechanism of efficacy.
O-Polysaccharide Glycosylation Is Required for Stability and Function of the Collagen Adhesin EmaA of Aggregatibacter actinomycetemcomitans
Authors: Tang Gaoyan , Ruiz Teresa , Mintz Keith P.
Published: June 2012

Aggregatibacter actinomycetemcomitans
is hypothesized to colonize through the interaction with collagen and establish a reservoir for further dissemination. The trimeric adhesin EmaA of
A. actinomycetemcomitans
binds to collagen and is modified with sugars mediated by an O-antigen polysaccharide ligase (WaaL) that is associated with lipopolysaccharide (LPS) biosynthesis (G. Tang and K. Mintz, J. Bacteriol.
192:
1395–1404, 2010). This investigation characterized the function and cellular localization of EmaA glycosylation. The interruption of LPS biogenesis by using genetic and pharmacological methods changed the amount and biophysical properties of EmaA molecules in the outer membrane. In
rmlC
and
waaL
mutant strains, the membrane-associated EmaA was reduced by 50% compared with the wild-type strain, without changes in mRNA levels. The membrane-associated EmaA protein levels were recovered by complementation with the corresponding O-polysaccharide (O-PS) biosynthetic genes. In contrast, another trimeric autotransporter, epithelial adhesin ApiA, was not affected in the same mutant background. The inhibition of undecaprenyl pyrophosphate recycling by bacitracin resulted in a similar decrease in the membrane-associated EmaA protein. This effect was reversed by removal of the compound. A significant decrease in collagen binding activity was observed in strains expressing the nonglycosylated form of EmaA. Furthermore, the electrophoretic mobility shifts of the EmaA monomers found in the O-PS mutant strains were associated only with the membrane-associated protein and not with the cytoplasmic pre-EmaA protein, suggesting that this modification does not occur in the cytoplasm. The glycan modification of EmaA appears to be required for collagen binding activity and protection of the protein against degradation by proteolytic enzymes.
Density functional theory for N–NO2 bond dissociation energies of N-nitroacylamide compounds in acetonitrile — Theoretical method assessment and prediction
Authors: Li Xiaohong , Wang Huixian , Fu Zhumu , Zhang Xianzhou
Published: June 2012

The performance of various density functional theories (B3LYP, B3PW91, B3P86, B1LYP, BMK, MPWB1K, PBE0, and MPWB95) was examined for calculating N–NO2 bond dissociation energies (BDEs) of 10 N-nitroacylamide compounds. The CBS-4M method was also used. By comparing the calculated results with the experimental values, it was observed that B1LYP/6–31G** and B3LYP/6–31+G** provided accurate BDEs. Especially, B3LYP/6–31+G** was recommended because of its smaller maximum absolute deviation. Further, substituent effects based on the B3LYP/6–31+G** method were analyzed. The result shows that an electron-donating group increases the BDE of the parent C6H5–CON(CH3)NO2, while an electron-withdrawing group decreases the BDE of the parent C6H5–CON(CH3)NO2. Subsequently, the BDEs of the other N-nitroacylamindes were estimated.
RELATIONSHIP BETWEEN APPLICABILITY OF CURRENT-BASED SYNAPSES AND UNIFORMITY OF FIRING PATTERNS
Authors: WONG W. K. , WANG Z. , ZHEN B. , LEUNG SYS.
Published: June 2012

The purpose of this paper is to identify situations in neural network modeling where current-based synapses are applicable. The applicability of current-based synapse model for studying post-transient behavior of neural networks is discussed in terms of average synaptic current strength induced by per spike during one firing cycle of a neuron (or briefly per spike synaptic current strength). It was found that current-based synapse models are applicable in both situations where both the interspike intervals of the neurons and the distribution of firing times of the neurons are uniform, and where the firing of all neurons is synchronized. If neither the interspike intervals nor the distribution of firing times of the neurons is uniform or the reversal potential is between the rest and threshold potentials, current-based synapse models may be oversimplified.
ON SHIFTED PRIMES AND BALANCED PRIMES
Authors: BROUGHAN KEVIN A.
Published: June 2012

The asymptotic order of the number of primes, which are such that the shift by a fixed integer is a number supported by a given set of primes times a coprime squarefree number, is determined. The order is also determined when the shift and its negative have this same shape. In each case the order is dependent only on the set of primes and the squarefree core of the shift.
SOME REMARKS ON RANKIN–COHEN BRACKETS OF EIGENFORMS
Authors: MEHER JABAN
Published: June 2012

We investigate the cases for which products of two quasimodular or nearly holomorphic eigenforms are eigenforms. We also generalize the results of Ghate [On products of eigenforms, Acta Arith.102 (2002) 27–44] to the case of Rankin–Cohen brackets.
Book Review: 'E-Learning and the Science of Instruction: Proven Guidelines for Consumers and Designers of Multimedia Learning (Essential Knowledge Resource)'
Authors: Layton-James Laura
Published: June 2012

Laura Layton-James checks out the latest edition of Clark and Mayer's book "E-Learning and the Science of Instruction" and explores the evidence-based research it offers. Her overview explores how the authors provide invaluable support for any instructional designer who wants to create engaging eLearning that delivers.
CFTR dysfunction predisposes to fibrotic liver disease in a murine model
Authors: Martin Camilia R. , Zaman Munir M. , Ketwaroo Gyanprakash A. , Bhutta Abdul Q. , Coronel Emmanuel , Popov Yury , Schuppan Detlef , Freedman Steven D.
Published: June 2012

Cystic fibrosis liver disease (CFLD) is a rapidly progressive biliary fibrosis, resembling primary sclerosing cholangitis that develops in 5–10% of patients with cystic fibrosis. Further research and evaluation of therapies are hampered by the lack of a mouse model for CFLD. Although primary sclerosing cholangitis is linked to both ulcerative colitis and loss of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function, induction of colitis with dextran sodium sulfate (DSS) in cftr−/− mice causes bile duct injury but no fibrosis. Since profibrogenic modifier genes are linked to CFLD, we examined whether subthreshhold doses of the profibrogenic xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), along with DSS-induced colitis, lead to bile duct injury and liver fibrosis in mice that harbor loss of CFTR function. Exon 10 heterozygous ( cftr+/−) and homozygous ( cftr−/−) mice treated with DDC demonstrated extensive mononuclear cell inflammation, bile duct proliferation, and periductular fibrosis. In contrast, wild-type ( cftr+/+) littermates did not develop bile duct injury or fibrosis. Histological changes corresponded to increased levels of alkaline phosphatase, hydroxyproline, and expression of profibrogenic transcripts for transforming growth factor-β1, transforming growth factor-β2, procollagen α1(I), and tissue inhibitor of matrix metaloproteinase-1. Immunohistochemistry demonstrated fibrosis and activation of periductal fibrogenic cells based on positive staining for lysyl oxidase-like-2, α-smooth muscle actin, and collagen I. These data demonstrate that subthreshold doses of DDC, in conjunction with DSS-induced colitis, results in bile duct injury and periductal fibrosis in mice with partial or complete loss of CFTR function and may represent a useful model to study the pathogenic mechanisms by which CFTR dysfunction predisposes to fibrotic liver disease and potential therapies.
Magnetic resonance assessment of parenchymal elasticity in normal and edematous, ventilator-injured lung
Authors: McGee Kiaran P. , Mariappan Yogesh K. , Hubmayr Rolf D. , Carter Rickey E. , Bao Zhonghao , Levin David L. , Manduca Armando , Ehman Richard L.
Published: June 2012

Magnetic resonance elastography (MRE) is a MR imaging method capable of spatially resolving the intrinsic mechanical properties of normal lung parenchyma. We tested the hypothesis that the mechanical properties of edematous lung exhibit local properties similar to those of a fluid-filled lung at transpulmonary pressures (Ptp) up to 25 cm H2O. Pulmonary edema was induced in anesthetized female adult Sprague-Dawley rats by mechanical ventilation to a pressure of 40 cm H2O for ∼30 min. Prior to imaging the wet weight of each ex vivo lung set was measured. MRE, high-resolution T1-weighted spin echo and T2* gradient echo data were acquired at each Ptpfor both normal and injured ex vivo lungs. At Ptps of 6 cm H2O and greater, the shear stiffness of normal lungs was greater than injured lungs ( P ≤ 0.0003). For Ptps up to 12 cm H2O, shear stiffness was equal to 1.00, 1.07, 1.16, and 1.26 kPa for the injured and 1.31, 1.89, 2.41, and 2.93 kPa for normal lungs at 3, 6, 9, and 12 cm H2O, respectively. For injured lungs MRE magnitude signal and shear stiffness within regions of differing degrees of alveolar flooding were calculated as a function of Ptp. Differences in shear stiffness were statistically significant between groups ( P < 0.001) with regions of lower magnitude signal being stiffer than those of higher signal. These data demonstrate that when the alveolar space filling material is fluid, MRE-derived parenchymal shear stiffness of the lung decreases, and the lung becomes inherently softer compared with normal lung.
Effects of Annealing Temperature on Structure and Magnetic Properties of TbxY3−xFe5O12 (x=0.2 and 0.4) Thin Films
Authors: Ibrahim N. B. , Aldbea Ftema W. , Abdullah Mustaffa Hj
Published: June 2012

Terbium‐substituted yttrium iron garnet (TbxY3−xFe5O12 (x = 0.2 and 0.4)) thin films have been successfully prepared by a sol‐gel method followed by spin‐coating process. The annealing of the films was performed at different temperatures like 700, 800, and 900°C and found that the films annealed at 900°C turned out to be crystallized into a pure garnet phase. All of the films were bearing grains of nanometer in size. Increasing the annealing temperature gave extra energy to the grains causing to be agglomerates. The lattice contraction occurred as the grain’s sizes were decreased due to the decrease of Fe2+ formation. The magnetic measurements show that all of the films are soft magnetic materials with low saturation magnetization values. The hysteresis loops of the films which were annealed at 900°C were found angular in shape similar to the single crystal‐like YIG film.
Evaluation of CdS Interfacial Layers in ZnO Nanowire/Poly(3‐Hexylthiophene) Solar Cells
Authors: Murphy John W. , Mejia Israel , Gnade Bruce E. , Quevedo-Lopez Manuel A.
Published: June 2012

We prepare ZnO:poly(3‐hexylthiophene) (P3HT) thin‐film solar cells and ZnO nanowire:P3HT nanostructured solar cells
and evaluate the effect of adding an interfacial layer between the ZnO and P3HT as a function of the nanowire height.
We evaluate several different interlayers of CdS deposited, using two different chemical bath deposition (CBD) recipes.
The height of the nanowire array is varied from a bilayer device with no nanowires up to arrays with a height of 2 μm.
We find that achieving a conformal coating of the ZnO with the interfacial layer is critical to improve device performance
and that CBD can be used to grow conformal films on nonuniform surfaces.
How to Safely Integrate Multiple Applications on Embedded Many-Core Systems by Applying the “Correctness by Construction” Principle
Authors: Hilbrich Robert
Published: June 2012

Software-intensive embedded systems, especially cyber-physical systems, benefit from the additional performance and the small power envelope offered by many-core processors. Nevertheless, the adoption of a massively parallel processor architecture in the embedded domain is still challenging. The integration of multiple and potentially parallel functions on a chip—instead of just a single function—makes best use of the resources offered. However, this multifunction approach leads to new technical and nontechnical challenges during the integration. This is especially the case for a distributed system architecture, which is subject to specific safety considerations. In this paper, it is argued that these challenges cannot be effectively addressed with traditional engineering approaches. Instead, the application of the “correctness by construction” principle is proposed to improve the integration process.
Strong Convergence Theorem for Solving Generalized Mixed Equilibrium Problems and Fixed Point Problems for Total Quasi‐ϕ‐Asymptotically Nonexpansive Mappings in Banach Spaces
Authors: Ma Zhaoli , Wang Lin , Zhao Yunhe
Published: June 2012

We introduce an iterative scheme for finding a common element of the set of solutions of generalized mixed equilibrium problems and the set of fixed points for countable families of total quasi‐ϕ‐asymptotically nonexpansive mappings in Banach spaces. We prove a strong convergence theorem of the iterative sequence generated by the proposed iterative algorithm in an uniformly smooth and strictly convex Banach space which also enjoys the Kadec‐Klee property. The results presented in this paper improve and extend some recent corresponding results.
Distinct Characteristics in Japanese Dermatitis Herpetiformis: A Review of All 91 Japanese Patients over the Last 35 Years
Authors: Ohata Chika , Ishii Norito , Hamada Takahiro , Shimomura Yutaka , Niizeki Hironori , Dainichi Teruki , Furumura Minao , Tsuruta Daisuke , Hashimoto Takashi
Published: June 2012

We reviewed all 91 Japanese dermatitis herpetiformis (DH) patients reported over the last 35 years. The male-to-female ratio was 2 : 1. The mean age at onset was 43.8, and 13 years earlier for female patients. More than half of these Japanese DH patients showed granular IgA deposition in the papillary dermis, and another one-third showed fibrillar IgA deposition. The male patients with granular IgA deposition were 10 years older than those with fibrillar deposition. Whereas patients with granular IgA deposition showed typical distribution of the skin lesions, the predilection sites of DH tended to be spared in patients with fibrillar IgA deposition. Only 3 patients had definite gluten-sensitive enteropathy. There was a statistical difference in the frequency of human leukocyte antigen (HLA)-DR9 between the granular group and controls among Japanese. No patients had HLA-DQ2 or -DQ8, which is frequently found in Caucasian DH patients. The absence of HLA-DQ2/DQ8, the inability to identify celiac disease in most cases, the predominance of fibrillar IgA, and the unusual distribution of clinical lesions in Japanese patients suggest that Japanese DH may be a subset of DH patients and have a pathogenesis which is different from that currently proposed in Caucasian DH patients.
Morphology and Properties of Nylon 6 Blown Films Reinforced with Different Weight Percentage of Nanoclay Additives
Authors: Hegde Raghavendra R. , Bhat Gajanan S. , Deshpande Bhushan
Published: June 2012

This article presents the effect of increasing weight percentage natural nanoclay additives on the structure, morphology and mechanical properties of nylon-6-blown films. Combination of X-ray diffraction, thermal analysis and microscopy were used to determine nanocomposite film morphology. The nanoclay additives in the films act as nucleating agent facilitatesγ-crystalline forms and results in fine grained spherulite with smaller lamellar size. Increase in tensile, burst, and tear strength is observed for films with up to 5% clay loading. Even though microscale property like tensile and tear strength drops at higher add on levels, near-surface nanoscale hardness and toughness of the film keep on increasing. There is a direct correlation between nanoclay additive add on level and increase in surface energy and wetting behavior of films.
BCL2 Suppresses PARP1 Function and Nonapoptotic Cell Death
Authors: Dutta Chaitali , Day Tovah , Kopp Nadja , van Bodegom Diederik , Davids Matthew S. , Ryan Jeremy , Bird Liat , Kommajosyula Naveen , Weigert Oliver , Yoda Akinori , Fung Hua , Brown Jennifer R. , Shapiro Geoffrey I. , Letai Anthony , Weinstock David M.
Published: June 2012

BCL2 suppresses apoptosis by binding the BH3 domain of proapoptotic factors and thereby regulating outer mitochondrial membrane permeabilization. Many tumor types, including B-cell lymphomas and chronic lymphocytic leukemia, are dependent on BCL2 for survival but become resistant to apoptosis after treatment. Here, we identified a direct interaction between the antiapoptotic protein BCL2 and the enzyme PARP1, which suppresses PARP1 enzymatic activity and inhibits PARP1-dependent DNA repair in diffuse large B-cell lymphoma cells. The BH3 mimetic ABT-737 displaced PARP1 from BCL2 in a dose-dependent manner, reestablishing PARP1 activity and DNA repair and promoting nonapoptotic cell death. This form of cell death was unaffected by resistance to single-agent ABT-737 that results from upregulation of antiapoptotic BCL2 family members. On the basis of the ability of BCL2 to suppress PARP1 function, we hypothesized that ectopic BCL2 expression would kill PARP inhibitor–sensitive cells. Strikingly, BCL2 expression reduced the survival of PARP inhibitor–sensitive breast cancer and lung cancer cells by 90% to 100%, and these effects were reversed by ABT-737. Taken together, our findings show that a novel interaction between BCL2 and PARP1 blocks PARP1 enzymatic activity and suppresses PARP1-dependent repair. Targeted disruption of the BCL2–PARP1 interaction therefore may represent a potential therapeutic approach for BCL2-expressing tumors resistant to apoptosis. Cancer Res; 72(16); 4193–203. ©2012 AACR.
The State of Molecular Biomarkers for the Early Detection of Lung Cancer
Authors: Hassanein Mohamed , Callison J. Clay , Callaway-Lane Carol , Aldrich Melinda C. , Grogan Eric L. , Massion Pierre P.
Published: June 2012

Using biomarkers to select the most at-risk population, to detect the disease while measurable and yet not clinically apparent has been the goal of many investigations. Recent advances in molecular strategies and analytic platforms, including genomics, epigenomics, proteomics, and metabolomics, have identified increasing numbers of potential biomarkers in the blood, urine, exhaled breath condensate, bronchial specimens, saliva, and sputum, but none have yet moved to the clinical setting. Therefore, there is a recognized gap between the promise and the product delivery in the cancer biomarker field. In this review, we define clinical contexts where risk and diagnostic biomarkers may have use in the management of lung cancer, identify the most relevant candidate biomarkers of early detection, provide their state of development, and finally discuss critical aspects of study design in molecular biomarkers for early detection of lung cancer. Cancer Prev Res; 5(8); 992–1006. ©2012 AACR.
Targeting FACT Complex Suppresses Mammary Tumorigenesis in Her2/neu Transgenic Mice
Authors: Koman Igor E. , Commane Mairead , Paszkiewicz Geraldine , Hoonjan Bhupinder , Pal Srabani , Safina Alfiya , Toshkov Ilya , Purmal Andrei A. , Wang Dan , Liu Song , Morrison Carl , Gudkov Andrei V. , Gurova Katerina V.
Published: June 2012

Development of safe and effective tumor-preventive treatments for high-risk patient populations and therapies for early-stage cancer remains a critical need in oncology. We have recently discovered compound with anticancer activity, Curaxin-137, which modulates several important signaling pathways involved in even the very early stages of cancer. In tumor cells, Curaxin-137 inhibits NF-κB- and HSF1-dependent transcription (prosurvival pathways) and activates p53 (a proapoptotic pathway) without inducing DNA damage. These effects result from chromatin trapping and inhibition of activity of the FACT (facilitates chromatin transcription) complex by Curaxin-137. FACT has not been previously implicated in cancer, but we found that its subunits are overexpressed in breast cancer. On the basis of this background, we tested whether Curaxin-137 could suppress tumorigenesis in MMTV-neu transgenic mice, which spontaneously develop mammary carcinoma due to steroid receptor–regulated expression of the Her2 proto-oncogene. We found that chronic administration of Curaxin-137 in a preventive regimen to MMTV-neu mice did not cause any detectable changes in normal organs and tissues, yet inhibited tumor onset, delayed tumor progression, and prolonged survival of mice in a dose-dependent manner. Curaxin-137 induced changes in FACT, altered NF-κB localization, and activated p53 in tumor cells as expected from its defined mechanism of action. These results support further investigation of Curaxin-137 as a potential preventive and/or early-stage therapeutic agent for breast cancer. Cancer Prev Res; 5(8); 1025–35. ©2012 AACR.
Neurodevelopmental Outcome of Infants Resuscitated with Air or 100% Oxygen: A Systematic Review and Meta-Analysis
Authors: Saugstad Ola Didrik , Vento Maximo , Ramji Siddarth , Howard Diantha , Soll Roger F.
Published: June 2012

Background: The use of air for the initial resuscitation of newborn infants has been shown to reduce neonatal mortality. However, a precise estimate of the neurodevelopmental status upon follow-up of infants resuscitated in air is lacking. Objective: To perform a meta-analysis of all studies reporting resuscitation of newborn infants with air or 100% oxygen that included follow-up data. Methods: Bibliographic databases were searched. In addition, we estimated the effect of loss to follow-up on our analysis of abnormal neurodevelopmental outcome. Results: We identified 10 studies in which newborn infants had been randomly or quasi-randomly assigned to resuscitation with air or 100% oxygen. Three of these 10 studies had available follow-up data. A total of 678 infants were enrolled at centers that performed follow-up of these infants. Of these, 113 died, leaving 565 infants potentially eligible for follow-up. A total of 414 children were evaluated (73% of eligible children; 195 resuscitated with air and 219 with 100% oxygen). In the air group, 12.8% of infants had an abnormal neurodevelopmental outcome, compared with 10.5% in the 100% oxygen group [typical relative risk (RR) 1.24, 95% confidence interval 0.73–2.10]. This is consistent with an RR of abnormal development as low as 0.41 or as high as 2.28. Conclusions: Long-term follow-up did not detect any significant differences in these two groups regarding abnormal development. However, the results are imprecise and could be consistent with significant harm or benefit.
The Prevalence of Hypertension, Valve Calcification and Left Ventricular Hypertrophy and Geometry in Peritoneal Dialysis Patients
Authors: Yilmaz Murvet , Unsal Abdulkadir , Oztekin Erkan , Kesmezacar Ozgu , Harmankaya Kaptanogullari Ozlem , Eren Nezaket
Published: June 2012

Background/Aims: Cardiac valve calcification (CVC) and left ventricular (LV) abnormalities are common indicators of a poor prognosis in dialysis patients. We determined the prevalence of hypertension, CVC, LV hypertrophy (LVH) and LV geometry in peritoneal dialysis (PD) patients. Methods: Eighty-seven patients (50 female; mean age 42 ± 13 years; mean dialysis duration 46 ± 24 months) on strict salt and volume restriction, none of whom were receiving antihypertensives, were included in the study. Blood pressure (BP), biochemical parameters, CVC, LVH and LV geometry were determined. Results: Most patients were normotensive. CVC of the mitral and aortic valves and of both valves were noted in 22, 23 and 15% of patients, respectively. Patients with CVC had significantly higher diastolic BP (p = 0.023), cardiothoracic index (CTI; p = 0.037) and LV mass index (LVMI; p = 0.002). LVH, noted overall in 44% of cases, was present in 62 and 36% of the patients with and without CVC, respectively (p = 0.028). Of the whole group, only 50.6% had normal LV geometry. LVH was associated with lower serum albumin (p = 0.002), higher CTI (p = 0.027) and more frequent CVC (p = 0.028). LVMI was greater in patients with CVC (p = 0.002). Conclusion: Strict salt restriction and the achievement of ideal dry weight result in normotension in PD patients. CVC is associated with LVH, both of which are lower in normotensive patients.
Incidence of Clostridium difficile Infection in Children with Inflammatory Bowel Disease Compared to Oncology and Immunocompetent Patients
Authors: Hojsak Iva , Ferenc Tea , Bojanić Katarina , Mišak Zrinjka , Močić Pavić Ana , Lukić-Grlić Amarela , Kolaček Sanja
Published: June 2012

Aims: The aim of this study was to determine the incidence of Clostridium difficile infection in hospitalized children with inflammatory bowel disease (IBD) and to compare it to other immunosuppressed patients at risk (oncology patients) as well as to immunocompetent patients. Methods: We analyzed data from all hospitalized children who underwent stool detection of C. difficile toxins A and B (n = 757) in a 5.5-year study period. Results: The number of positive tests was significantly increased in the oncology group compared to the IBD group (12.45 vs. 6.02%, p = 0.03) and immunocompetent group (12.45 vs. 5.7%, p = 0.01). Patients who had C. difficile infection used antibiotics prior to the test more often than patients who did not (12.69 vs. 1.73%, p = 0.03). Pearson’s correlation was positive for C. difficile infection and both antibiotics and immunosuppressants, while no correlation was found regarding age and gender. There were no significant differences regarding either IBD diagnosis (Crohn’s disease vs. ulcerative colitis, p = 0.71) or treatment used for IBD (p = 0.53) and C. difficile infection. Conclusion: In our setting, the incidence of C. difficile infection among hospitalized children with active IBD was found to be low. Children at increased risk for C. difficile infection were oncology patients receiving immunosuppressants and antibiotics.
Urate Transporter Gene SLC22A12 Polymorphisms Associated with Obesity and Metabolic Syndrome in Caucasians with Hypertension
Authors: Shafiu Mohamed , Johnson Richard J. , Turner Stephen T. , Langaee Taimour , Gong Yan , Chapman Arlene B. , Gums John G. , Johnson Julie A.
Published: June 2012

Background/Aims: Hyperuricemia is associated with obesity and the metabolic syndrome. URAT1 is a urate transporter, and we tested the association of URAT1 transporter gene (SLC22A12) polymorphisms with obesity and the metabolic syndrome in hypertensive subjects. Methods: Patients with essential hypertension (n = 414) from a randomized controlled study were genotyped for SLC22A12 SNPs rs11602903, rs505802 and rs11231825. Results: In Caucasians, SLC22A12 SNPs were associated with the body mass index (BMI). rs11602903 was associated with BMI (p < 0.0001), waist circumference (p = 0.003), HDL cholesterol (p = 0.018) and the metabolic syndrome (p = 0.033), and accounted for 7% of the variation of BMI in Caucasians. In African Americans, SLC22A12 SNP rs11602903 was not associated with BMI, waist circumference, HDL cholesterol or triglycerides. Conclusion:  The URAT1 gene SLC22A12 polymorphism may play a role in obesity and the metabolic syndrome in Caucasian hypertensive subjects.
Induction of Glucose Intolerance by Acute Administration of Rimonabant
Authors: Mandhane Sanjay , Nayak Prasanta , Soni Durgesh , Jain Shakti , Ashton John C. , Rajamannar Thennati
Published: June 2012

Background/Aims: Rimonabant is a cannabinoid CB1 receptor antagonist. Other CB1 antagonists have biphasic effects on blood glucose levels following acute administration. We therefore tested the effects of rimonabant on glucose tolerance following acute administration. Methods: We tested the effects of oral and intracerebroventricular administration of rimonabant on blood glucose and gastrointestinal transit in mice following oral and intravenous glucose challenge. Results: We found a dose-dependent increase in blood glucose from oral doses of rimonabant of 3 mg/kg and above. WIN55,212-2 (3 mg/kg), a cannabinoid receptor agonist, did not influence blood glucose in the presence or absence of rimonabant. Rimonabant did not induce release of glucose from isolated rat hepatocytes or modify serum insulin concentration in mice. Intracerebroventricular administration of rimonabant caused increases in blood glucose and gastrointestinal transit, suggesting a central nervous system site of action. Increases in blood glucose by rimonabant were partially blocked by the dopamine receptor antagonist haloperidol and significantly blocked by the 5-hydroxytryptophan (5-HT) depleting agent p-CPA and the 5-HT3 receptor antagonist ondansetron. Conclusions: Rimonabant causes a dose-dependent increase in glucose profile upon glucose challenge partially mediated by the central nervous system control of gastrointestinal carbohydrate absorption through pathways that are modulated by both 5-HT and dopamine.
New Trends to Support Independence in Persons with Mild Dementia – A Mini-Review
Authors: Mokhtari M. , Aloulou H. , Tiberghien T. , Biswas J. , Racoceanu D. , Yap P.
Published: June 2012

Our research was motivated by the growing aging population worldwide and the need to concentrate research efforts on a specific target group; it focuses on elderly persons with physical and cognitive deficiencies. The primary goal is to enable persons with mild dementia to maximize their physical and mental functions through assistive technologies in order to be able to continue to participate in social networks and lead independent and purposeful lives. Persons with mild dementia usually have problems in performing activities of daily living due to episodic memory decline. These can include simple activities, such as bathing, changing clothes and preparing meals. Through extended field test trials involving end users, we have demonstrated that assistive technology that provides timely prompts, alarms and reminders can enable them to preserve their abilities and improve their quality of life. Understanding the user context, especially when targeting demented individuals, and providing the required personalized assistive services is the objective of our research work. Finding the appropriate user interface to interact with the provided services is often a barrier. Thus, we have adopted the approach of a multimodal interactive system with the living environment including a TV set, iPad-like tablets, sensors/actuators, and wireless speakers connected to a reasoning engine that is able to consider the complexity of the users’ profile defined by his/her cognitive abilities. In this paper we will mainly focus on the interaction level with the system as well as on the validation stages performed to meet the users’ requirements. This is the result of several years’ work since 2006 in the frame of two projects (IST-FP6 COGKNOW European completed project and AMUPADH ongoing project in Singapore).
Protective Effect of the Grape Seed Proanthocyanidin Extract in a Rat Model of Contrast-Induced Nephropathy
Authors: Ozkan Gulsum , Ulusoy Sukru , Orem Asım , Ersoz Safak , Alkanat Mehmet , Yucesan Fulya Balaban , Kaynar Kubra , Al Sait
Published: June 2012

Aim: Contrast-induced nephropathy (CIN) is a common cause of hospital-acquired acute renal failure. Although it is so common, there has been no approved therapy yet. We aimed to investigate the effect of grape seed proanthocyanidin extract (GSPE) on preventing CIN. Materials and Methods: 24 rats were divided into four groups as control group, GSPE group, contrast medium (CM) group, and CM+GSPE group. The experiment was discontinued on the ninth day. Blood samples were obtained for the measurement of renal function parameters. Renal tissues of the rats were removed for the analysis of oxidative system parameters. In addition to renal histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis. Results: There was a significant increase in BUN, creatinine, malondialdehyde (MDA) levels, apoptotic index (AI) and histopathological alteration in the CM group as compared to the control group. Furthermore, BUN, creatinine, MDA, total oxidant system and oxidative stress index levels, AI as well as renal histopathological alteration were significantly decreased in the CM+GSPE group. Conclusion: For the first time in the literature, we showed that GSPE provided biochemical and histopathological improvement in CIN. Our findings revealed that this improvement was associated with the decrease in oxidative damage and apoptosis.
Clinical Safety Assessment of Infant Nutrition
Authors: Fewtrell M.S.
Published: June 2012

Data on clinical safety and efficacy are ideally collected in a randomized clinical trial or, failing this, an observational study. Suitable outcomes vary depending on the intervention and population group, and certain outcomes such as growth may test both efficacy and safety. The use of growth as an important safety outcome has some limitations since it is currently not clear what represents an ‘optimal’ growth pattern. Several issues currently make the conduct and interpretation of infant nutrition trials challenging. These include difficulties in recruiting exclusively formula-fed infants, particularly given the emotive nature of infant feeding; the involvement of industry leading to real or perceived conflicts of interest; increased regulation and bureaucracy; and particular issues with long-term follow-up studies, notably cohort attrition. This paper addresses the implications of these issues and some potential solutions.
Laser Interstitial Thermal Therapy for Focal Cerebral Radiation Necrosis: A Case Report and Literature Review
Authors: Rahmathulla Gazanfar , Recinos Pablo F. , Valerio Jose E. , Chao Sam , Barnett Gene H.
Published: June 2012

Whole-brain radiotherapy and stereotactic radiosurgery (SRS) play a central role in the treatment of metastatic brain tumors. Radiation necrosis occurs in 5% of patients and can be very difficult to treat. The available treatment options for radiation necrosis include prolonged high-dose corticosteroids, hyperbaric oxygen, anticoagulation, bevacizumab, and surgical resection. We present the first report and results using laser-interstitial thermal therapy (LITT) for medically refractory radionecrosis. A 74-year-old diabetic patient who had a history of non-small cell lung cancer with brain metastases and subsequent treatment with SRS, presented with a focal lesion in the left centrum semiovale with progressively worsening edema. Image findings were consistent with radiation necrosis that was refractory despite prolonged, high-dose steroid therapy. His associated comorbidities obviated alternative interventions and the lesion was not in a location amenable to surgical resection. We used laser thermal ablation to treat the biopsy-proven radionecrosis. The procedure was tolerated well and the patient was discharged 48 hours postoperatively. Imaging at 7-week follow-up showed near complete resolution of the edema and associated mass effect. Additionally, the patient was completely weaned off steroids. To our knowledge this is the first report using LITT for the treatment of focal radiation necrosis. LITT may be an effective treatment modality for patients with medically refractory radiation necrosis with lesions not amenable to surgical decompression.
No Evidence for an Epidemic of Stroke with the Ageing of the Population
Authors: Thrift Amanda G. , Tong Bin , Senes Susana , Waters Anne-Marie , Lalor Erin
Published: June 2012

Background/Aim: The ageing population in Australia may contribute to an epidemic of stroke in coming years. We aimed to assess whether deaths and hospitalisations from stroke in Australia are increasing. Methods: Nationwide age- and sex-specific hospitalisation episode data from 1996 to 1997 were used to predict future hospitalisations from stroke. Age- and sex-specific mortality data from 1997 were used to predict future mortality from stroke. These predictions were based on an expected increase in the population’s age and population growth. We compared these estimates to those observed in national figures for the following 9 years. Results: Based on 1996–1997 hospitalisation rates, we calculated that hospitalisations for stroke would be expected to rise from 27,399 to 35,041 in 2005–2006. Using 1997 mortality rates, deaths from stroke would be expected to rise from 9,126 to 12,726 in 2007. Observed hospitalisations (2005–2006) were 6,380 fewer than expected, while deaths (2007) were 4,103 fewer than expected. This represents a 2.21% annual reduction in hospitalisation rate, and a 4.0% annual reduction in mortality rate. Conclusion: Encouragingly, hospitalisation and mortality rates for stroke appear to be declining. If these figures reflect actual occurrences of stroke then it may be that primary and secondary prevention strategies are working.
The Peptide Nucleic Acid-Locked Nucleic Acid Polymerase Chain Reaction Clamp-Based Test for Epidermal Growth Factor Receptor Mutations in Bronchoscopic Cytological Specimens of Non-Small Cell Lung Cancer
Authors: Yamada Noriyuki , Oizumi Satoshi , Asahina Hajime , Shinagawa Naofumi , Kikuchi Eiki , Kikuchi Junko , Sakakibara-Konishi Jun , Tanaka Tomoaki , Kobayashi Kunihiko , Hagiwara Koichi , Nishimura Masaharu
Published: June 2012

Objectives: Cytological examination of samples obtained by bronchoscopy is a useful method for establishing the diagnosis of non-small cell lung cancer (NSCLC). However, the utility of a highly sensitive method for the detection of epidermal growth factor receptor (EGFR) mutation in the cytological specimens has not been fully evaluated. Methods: We retrospectively examined the efficacy of the peptide nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp method for detecting EGFR mutations in 122 bronchoscopic cytological specimens from NSCLC patients. Results: Overall, 41 specimens (33.6%) were positive for EGFR mutation. Twenty-nine (39.7%) of 73 specimens obtained by using endobronchial ultrasonography with a guide sheath, 7 (33.3%) of 21 specimens obtained under direct vision by using a conventional bronchoscope, 4 (36.4%) of 11 specimens obtained by using an ultrathin bronchoscope, and 1 (5.9%) of 17 specimens obtained by endobronchial ultrasound-guided transbronchial needle aspiration were positive for EGFR mutation. Furthermore, among 22 resected NSCLC cases, the EGFR mutation status obtained from bronchoscopic materials was consistent with the status obtained from surgical samples, with the exception of 1 case. Conclusion: The detection of EGFR mutation by subjecting bronchoscopic cytological specimens to a PNA-LNA PCR clamp assay proves useful.
Depressive Symptoms and Untreated Dental Caries in Older Independently Living South Brazilians
Authors: Hugo F.N. , Hilgert J.B. , de Sousa M.d.L.R. , Cury J.A.
Published: June 2012

Background: The importance of psychological reactions in modifying oral health behaviors and salivary immunity has been shown previously, but few studies assessed whether psychological reactions are associated with caries in populations. Thus, the aim of this study was to examine the association of depressive symptoms with untreated caries using a hierarchal approach. Methods: In this cross-sectional study, a random sample of 390 South Brazilians aged 60 years or more was evaluated using a structured questionnaire assessing sociodemographic, behavior, health and depressive symptoms (Geriatric Depression Scale) data. Oral examinations were carried out in order to assess: (1) dental status, using the DMFT index; (2) dental plaque, using the Visible Plaque Index, and (3) unstimulated saliva flow, using the spit method. A hierarchical model based on the framework of caries was carried out to assess whether depressive symptoms were associated with prevalent untreated dental caries (or D >0). Results: Depressive symptoms, number of teeth and plaque accumulation were significant predictors of caries with respect to the D >0 outcome. Conclusion: Our findings suggest that depressive symptoms may act as determinants of caries, adding to the body of knowledge supporting the importance of psychological reactions in oral health/disease processes.
Molecular and Clinical Characteristics of 26 Cases with Structural Y Chromosome Aberrations
Authors: Kim J.-W. , Park S.-Y. , Ryu H.-M. , Lee D.-E. , Lee B.-Y. , Kim S.-Y. , Park Y.-S. , Lee H.-S. , Seo J.-T.
Published: June 2012

Structural abnormalities include various types of translocations, inversions, deletions, duplications and isochromosomes. Structural abnormalities of the Y chromosome are estimated to affect less than 1% of the newborn male population and are particularly hazardous for male reproductive function. The objective of this study was to characterize a group of patients with structural abnormalities of the Y chromosome. All patients who visited our laboratory between 2007 and 2010 underwent cytogenetic investigations. Among these, we detected 26 patients with structural abnormalities of the Y chromosome. To confirm the structural Y chromosome alterations, we used special bandings, FISH and multiplex PCR to detect Y chromosome microdeletions. Of the 26 patients presented here, 11 had an isodicentric Y chromosome, 7 had an inversion, 3 had a translocation, 2 had a derivative, 2 had a Yqs and 1 had a deletion. Sixteen were diagnosed with azoospermia, 8 as normal fertile males and 1 as a man who was unable to donate semen due to mental retardation. One of the patients having 45,X/46,X,idic(Y) was reported to be phenotypically female with primary amenorrhea and without uterus. Deletions of the AZFbc region were correlated with the sperm concentration (p < 0.05), but no correlation with the levels of FSH, LH, testosterone, prolactin and estradiol were found. The present report shows that the precise identification of structural Y chromosome aberrations may be clinically important for genetic counseling and assisted reproductive technology treatment.