bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative trait loci associated with murine central corneal thickness
Authors: Lively Geoffrey D. , Koehn Demelza , Hedberg-Buenz Adam , Wang Kai , Anderson Michael G.
Published: April 2010

The cornea is a specialized transparent tissue responsible for refracting light, serving as a protective barrier, and lending structural support to eye shape. Given its importance, the cornea exhibits a surprising amount of phenotypic variability in some traits, including central corneal thickness (CCT). More than a mere anatomic curiosity, differences in CCT have recently been associated with risk for glaucoma. Although multiple lines of evidence support a strong role for heredity in regulating CCT, the responsible genes remain unknown. To better understand the genetic basis of CCT variability, we conducted a genomewide quantitative trait locus (QTL) analysis with (C57BLKS/J × SJL/J) F2mice. This experiment identified a locus, Cctq1 (central corneal thickness QTL 1) on chromosome 7 (Chr 7; peak, 105 Mb), that is significantly associated with CCT. To independently test the biological significance of these results, (C57BLKS/J × NZB/B1NJ) F2mice were generated and analyzed for associations with Chr 7. This experiment identified a significant association at 131 Mb. Furthermore, low-generation congenic mice in which the Chr 7 QTL interval from the SJL strain was transferred onto the KS background had CCT values significantly higher than inbred KS mice. These results demonstrate that the genetic dependence of CCT in mice is a multigenic trait, which in these contexts is significantly regulated by a region on Chr 7. Future identification of the genes for these QTL will provide improved understanding of the processes regulating CCT and the pathophysiology of glaucoma.
A Comparative Study between the Effects of Magnetic and Nonmagnetic Dopants on the Properties of ZnO Varistors
Authors: Sedky A. , El-Suheel E.
Published: April 2010

A comparative study between effects of Mn and Al on the properties of ZnO varistor sintered at 1200 is investigated by XRD, SEM hardness, and I-V measurements. Although both Mn and Al do not influence the well-known peaks related to wurtzite structure of ZnO ceramics, some other unknown peaks could be formed at higher doping content (). Also, the shape and size of grains are clearly different for both dopants. Average crystalline diameters, deduced
from XRD analysis, are between 42 nm and 62 nm, which are 50 times lower than those obtained from SEM micrographs, while the oxygen vacancies deduced from EDAX analysis, are gradually decreased by doping content for both dopants.
Interestingly, the values of breakdown field, nonlinear coefficient and barrier height are found to be higher in Mn samples as compared to Al samples, while the opposite is reported for leakage currents, hardness, and electrical conductivities. The values of
are changed from 2.67 V/cm to 41.67 V/cm for Al, and from 1928 V/cm to 6571 V/cm for Mn. The conductivity of Al samples is higher than that of ZnO, and it is nearly (103–105) times the conductivity of Mn samples. These
results are discussed in terms of the difference of magnetic moment and valence state between these two additives.
Matrix Metalloproteinase-14 (MT1-MMP)–Mediated Endoglin Shedding Inhibits Tumor Angiogenesis
Authors: Hawinkels Lukas J.A.C. , Kuiper Patricia , Wiercinska Eliza , Verspaget Hein W. , Liu Zhen , Pardali Evangelia , Sier Cornelis F.M. , ten Dijke Peter
Published: April 2010

Endoglin is a transforming growth factor-β coreceptor with a crucial role in angiogenesis. A soluble form of endoglin is present in the circulation, but the role of soluble endoglin (sEndoglin) is poorly understood. In addition, the endoglin shedding mechanism is not known. Therefore, we examined the role of sEndoglin in tumor angiogenesis and the mechanism by which the extracellular domain of endoglin is released from the membrane.In colorectal cancer specimens, we observed high endothelial endoglin protein expression, accompanied with slightly lower sEndoglin levels in the circulation, compared with healthy controls. In vitro analysis using endothelial sprouting assays revealed that sEndoglin reduced spontaneous and vascular endothelial growth factor–induced endothelial sprouting. Human umbilical vascular endothelial cells were found to secrete high levels of sEndoglin. Endoglin shedding was inhibited by matrix metalloproteinase (MMP) inhibitors and MMP-14 short hairpin RNA, indicating MMP-14 as the major endoglin shedding protease. Coexpression of endoglin and membrane-bound MMP-14 led to a strong increase in sEndoglin levels. Endoglin shedding required a direct interaction between endoglin and membrane-localized MMP-14. Using cleavage site mutants, we determined that MMP-14 cleaved endoglin at a site in close proximity to the transmembrane domain. Taken together, this study shows that MMP-14 mediates endoglin shedding, which may regulate the angiogenic potential of endothelial cells in the (colorectal) tumor microenvironment. Cancer Res; 70(10); 4141–50. ©2010 AACR.
Identification of the ENT1 Antagonists Dipyridamole and Dilazep as Amplifiers of Oncolytic Herpes Simplex Virus-1 Replication
Authors: Passer Brent J. , Cheema Tooba , Zhou Bingsen , Wakimoto Hiroaki , Zaupa Cecile , Razmjoo Mani , Sarte Jason , Wu Shulin , Wu Chin-lee , Noah James W. , Li Qianjun , Buolamwini John K. , Yen Yun , Rabkin Samuel D. , Martuza Robert L.
Published: April 2010

Oncolytic herpes simplex virus-1 (oHSV) vectors selectively replicate in tumor cells, where they kill through oncolysis while sparing normal cells. One of the drawbacks of oHSV vectors is their limited replication and spread to neighboring cancer cells. Here, we report the outcome of a high-throughput chemical library screen to identify small-molecule compounds that augment the replication of oHSV G47Δ. Of the 2,640-screened bioactives, 6 compounds were identified and subsequently validated for enhanced G47Δ replication. Two of these compounds, dipyridamole and dilazep, interfered with nucleotide metabolism by potently and directly inhibiting the equilibrative nucleoside transporter-1 (ENT1). Replicative amplification promoted by dipyridamole and dilazep were dependent on HSV mutations in ICP6, the large subunit of ribonucleotide reductase. Our results indicate that ENT1 antagonists augment oHSV replication in tumor cells by increasing cellular ribonucleoside activity. Cancer Res; 70(10); 3890–5. ©2010 AACR.
Inhibition of Mer and Axl Receptor Tyrosine Kinases in Astrocytoma Cells Leads to Increased Apoptosis and Improved Chemosensitivity
Authors: Keating Amy K. , Kim Grace K. , Jones Ashley E. , Donson Andrew M. , Ware Kathryn , Mulcahy Jean M. , Salzberg Dana B. , Foreman Nicholas K. , Liang Xiayuan , Thorburn Andrew , Graham Douglas K.
Published: April 2010

Astrocytomas account for the majority of malignant brain tumors diagnosed in both adult and pediatric patients. The therapies available to treat these neoplasms are limited, and the prognosis associated with high-grade lesions is extremely poor. Mer (MerTK) and Axl receptor tyrosine kinases (RTK) are expressed at abnormally high levels in a variety of malignancies, and these receptors are known to activate strong antiapoptotic signaling pathways that promote oncogenesis. In this study, we found that Mer and Axl mRNA transcript and protein expression were elevated in astrocytic patient samples and cell lines. shRNA-mediated knockdown of Mer and Axl RTK expression led to an increase in apoptosis in astrocytoma cells. Apoptotic signaling pathways including Akt and extracellular signal–regulated kinase 1/2, which have been shown to be activated in resistant astrocytomas, were downregulated with Mer and Axl inhibition whereas poly(ADP-ribose) polymerase cleavage was increased. Furthermore, Mer and Axl shRNA knockdown led to a profound decrease of astrocytoma cell proliferation in soft agar and a significant increase in chemosensitivity in response to temozolomide, carboplatin, and vincristine treatment. Our results suggest Mer and Axl RTK inhibition as a novel method to improve apoptotic response and chemosensitivity in astrocytoma and provide support for these oncogenes as attractive biological targets for astrocytoma drug development. Mol Cancer Ther; 9(5); 1298–307. ©2010 AACR.
Synergistic Antitumor Effect of S-1 and HER2-Targeting Agents in Gastric Cancer withHER2Amplification
Authors: Tanizaki Junko , Okamoto Isamu , Takezawa Ken , Tsukioka Sayaka , Uchida Junji , Kiniwa Mamoru , Fukuoka Masahiro , Nakagawa Kazuhiko
Published: April 2010

Amplification of human epidermal growth factor receptor 2 (HER2) has been detected in 20% to 30% of gastric cancers and is associated with a poor outcome. Combination therapies with HER2-targeting agents and cytotoxic agents are considered a potential therapeutic option for gastric cancer with HER2 amplification. We have now investigated the effects of combination treatment with the oral fluoropyrimidine S-1 and the HER2-targeting agents lapatinib or trastuzumab in gastric cancer cells with or without HER2 amplification. We used 5-fluorouracil (5FU) instead of S-1 for in vitro experiments, given that tegafur, a component of S-1, is metabolized to 5FU in the liver. The combination of 5FU and HER2-targeting agents synergistically inhibited cell proliferation and exhibited an enhanced proapoptotic effect in gastric cancer cells with HER2 amplification, but not in those without it. Lapatinib or trastuzumab also induced downregulation of thymidylate synthase (TS) expression and activity only in cells with HER2 amplification. The combination of 5FU and TS depletion by RNA interference also exhibited an enhanced proapoptotic effect in cells with HER2 amplification. These observations thus suggest that lapatinib-induced or trastuzumab-induced downregulation of TS is responsible, at least in part, for the synergistic antitumor effect of combined treatment with 5FU and HER2-targeting agents. The antitumor effect of the combination of S-1 and HER2-targeting agents in vivo was also greater than that of either drug alone. Our preclinical findings thus indicate that the combination of S-1 and HER2-targeting agents is a promising treatment option for gastric cancer with HER2 amplification. Mol Cancer Ther; 9(5); 1198–207. ©2010 AACR.
Effects of Short-term Celecoxib Treatment in Patients with Invasive Transitional Cell Carcinoma of the Urinary Bladder
Authors: Dhawan Deepika , Craig Bruce A. , Cheng Liang , Snyder Paul W. , Mohammed Sulma I. , Stewart Jane C. , Zheng Rong , Loman Rhoda A. , Foster Richard S. , Knapp Deborah W.
Published: April 2010

High-grade invasive transitional cell carcinoma (InvTCC) kills >14,000 people yearly in the United States, and better therapy is needed. Cyclooxygenase-2 (Cox-2) is overexpressed in bladder cancer. Cox inhibitors have caused remission of InvTCC in animal studies, and cancer regression was associated with doubling of the apoptotic index in the tumor. The purpose of this study was to determine the apoptosis-inducing effects of celecoxib (a Cox-2 inhibitor) in InvTCC in humans. Patients (minimum of 10 with paired tumor samples) with InvTCC who had elected to undergo cystectomy were enrolled. The main study end point was induction of apoptosis in tumor tissues. Patients received celecoxib (400 mg twice daily p.o. for a minimum of 14 days) between the time of diagnosis [transurethral resection of bladder tumor (TURBT)] and the time of cystectomy (standard frontline treatment for InvTCC). Terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling assay and immunohistochemistry were done on TURBT and cystectomy samples. Of 13 cases treated with celecoxib, no residual invasive cancer was identified in 3 patients at the time of cystectomy (post celecoxib). Of the 10 patients with residual cancer, 7 had induction of apoptosis in their tumor. Induction of apoptosis was less frequent (3 of 13 cases; P < 0.04) in control patients not receiving a Cox inhibitor. Expression of vascular endothelial growth factor in the tumor cells decreased more frequently (P < 0.026) in the treated patients as compared with nontreated control cases. The biological effects of celecoxib treatment (increased apoptosis) justify further study of the antitumor effects of Cox-2 inhibitors in InvTCC. Mol Cancer Ther; 9(5); 1371–7. ©2010 AACR.
Blood Biomarker Levels to Aid Discovery of Cancer-Related Single-Nucleotide Polymorphisms: Kallikreins and Prostate Cancer
Authors: Klein Robert J. , Halldén Christer , Cronin Angel M. , Ploner Alexander , Wiklund Fredrik , Bjartell Anders S. , Stattin Pär , Xu Jianfeng , Scardino Peter T. , Offit Kenneth , Vickers Andrew J. , Grönberg Henrik , Lilja Hans
Published: April 2010

Polymorphisms associated with prostate cancer include those in three genes encoding major secretory products of the prostate: KLK2 (encoding kallikrein-related peptidase 2; hK2), KLK3 (encoding prostate-specific antigen; PSA), and MSMB (encoding β-microseminoprotein). PSA and hK2, members of the kallikrein family, are elevated in sera of men with prostate cancer. In a comprehensive analysis that included sequencing of all coding, flanking, and 2 kb of putative promoter regions of all 15 kallikrein (KLK) genes spanning ≈280 kb on chromosome 19q, we identified novel single-nucleotide polymorphisms (SNP) and genotyped 104 SNPs in 1,419 cancer cases and 736 controls in Cancer Prostate in Sweden 1, with independent replication in 1,267 cases and 901 controls in Cancer Prostate in Sweden 2. This verified prior associations of SNPs in KLK2 and in MSMB (but not in KLK3) with prostate cancer. Twelve SNPs in KLK2 and KLK3 were associated with levels of PSA forms or hK2 in plasma of control subjects. Based on our comprehensive approach, this is likely to represent all common KLK variants associated with these phenotypes. A T allele at rs198977 in KLK2 was associated with increased cancer risk and a striking decrease of hK2 levels in blood. We also found a strong interaction between rs198977 genotype and hK2 levels in blood in predicting cancer risk. Based on this strong association, we developed a model for predicting prostate cancer risk from standard biomarkers, rs198977 genotype, and rs198977 × hK2 interaction; this model had greater accuracy than did biomarkers alone (area under the receiver operating characteristic curve, 0.874 versus 0.866), providing proof in principle to clinical application for our findings. Cancer Prev Res; 3(5); 611–9. ©2010 AACR.
Dysarthria in Friedreich’s Ataxia: A Perceptual Analysis
Authors: Folker Joanne , Murdoch Bruce , Cahill Louise , Delatycki Martin , Corben Louise , Vogel Adam
Published: April 2010

The aims of this study were to: (1) evaluate the perceptual speech dimensions, speech intelligibility and dysarthria severity of a group of individuals diagnosed with Friedreich’s ataxia (FRDA); (2) determine the presence of subgroups within FRDA dysarthria; (3) investigate the relationship between the speech outcome and the clinical factors of disease progression. The study included 38 individuals (21 female, 17 male) with a confirmed diagnosis of FRDA. A group of 20 non-neurologically impaired individuals served as controls. Perceptual analysis, investigating 30 different dimensions of speech, was conducted on a speech sample obtained from each participant. In addition, the Assessment of Intelligibility of Dysarthria Speech was administered. All FRDA participants presented with dysarthria with severities ranging from mild to moderate. Cluster analysis revealed 3 subgroups, the first presenting with mild dysarthric symptoms, the second with increased velopharyngeal involvement and the third characterized by increased laryngeal dysfunction. Dysarthria severity showed a significant correlation to disease duration but to no other clinical measure. The findings support the notion of subgroups in FRDA dysarthria, representing distinct impairments of the speech mechanism and perhaps reflective of differing evolutions beyond the cerebellum.
Effect of Rate Control on Speech Production and Intelligibility in Dysarthria
Authors: Van Nuffelen Gwen , De Bodt Marc , Vanderwegen Jan , Van de Heyning Paul , Wuyts Floris
Published: April 2010

The reported study investigated the effect of 7 rate control methods (RCM) on running speech intelligibility, speaking rate (SR), articulation rate (AR) and pause characteristics in 27 individuals with dysarthria. The data reveal that with the exception of slower on demand, each RCM resulted in lower mean SRs and ARs (p < 0.05). Clinically significant improvements in intelligibility were found in half of the participants with different types of dysarthria. The majority of them had normal or decreased ARs and SRs. The most effective methods were: alphabet board, hand tapping and pacing board. For the majority of speakers, the maximal decrease in speech rate was not associated with the maximal increase in intelligibility.
Transposable Elements in Reptilian and Avian (Sauropsida) Genomes
Authors: Kordis D.
Published: April 2010

Transposable elements (TEs) have profound effects on the structure, function and evolution of their host genomes. Our knowledge about these agents of genomic change in sauropsids, a sister group of mammals that includes all extant reptiles and birds, is still very limited. Invaluable information concerning the diversity, activity and repetitive landscapes in sauropsids has recently emerged from analyses of the draft genomes of chicken and Anolis and other preliminary reptilian genome sequencing projects. Avian and reptilian genomes differ significantly in the classes of TEs present, their fractional representation in the genome and by the level of TE activity. While lepidosaurian genomes contain many young, active TE families, the extant avian genomes have very few active TE lineages. Most reptilian genomes possess quite rich TE repertoires that differ considerably from those of birds and mammals, being more similar in diversity to that of lower vertebrates. The large amount of recently accumulated genome-wide data on TEs in diverse lineages of sauropsids has provided a remarkable opportunity to review current knowledge about TEs of sauropsids in their genomic context.
Dynamic Nucleotide Mutation Gradients and Control Region Usage in Squamate Reptile Mitochondrial Genomes
Authors: Castoe T.A. , Gu W. , de Koning A.P.J. , Daza J.M. , Jiang Z.J. , Parkinson C.L. , Pollock D.D.
Published: April 2010

Gradients of nucleotide bias and substitution rates occur in vertebrate mitochondrial genomes due to the asymmetric nature of the replication process. The evolution of these gradients has previously been studied in detail in primates, but not in other vertebrate groups. From the primate study, the strengths of these gradients are known to evolve in ways that can substantially alter the substitution process, but it is unclear how rapidly they evolve over evolutionary time or how different they may be in different lineages or groups of vertebrates. Given the importance of mitochondrial genomes in phylogenetics and molecular evolutionary research, a better understanding of how asymmetric mitochondrial substitution gradients evolve would contribute key insights into how this gradient evolution may mislead evolutionary inferences, and how it may also be incorporated into new evolutionary models. Most snake mitochondrial genomes have an additional interesting feature, 2 nearly identical control regions, which vary among different species in the extent that they are used as origins of replication. Given the expanded sampling of complete snake genomes currently available, together with 2 additional snakes sequenced in this study, we reexamined gradient strength and CR usage in alethinophidian snakes as well as several lizards that possess dual CRs. Our results suggest that nucleotide substitution gradients (and corresponding nucleotide bias) and CR usage is highly labile over the ∼200 m.y. of squamate evolution, and demonstrates greater overall variability than previously shown in primates. The evidence for the existence of such gradients, and their ability to evolve rapidly and converge among unrelated species suggests that gradient dynamics could easily mislead phylogenetic and molecular evolutionary inferences, and argues strongly that these dynamics should be incorporated into phylogenetic models.
The NIH Stroke Scale Can Establish Cognitive Function after Stroke
Authors: Cumming Toby B. , Blomstrand Christian , Bernhardt Julie , Linden Thomas
Published: April 2010

Background: Cognitive impairment is an important but underrecognised consequence of stroke. We investigated whether a subset of items from the NIH Stroke Scale (NIHSS) could yield valid information on cognitive status in a group of stroke patients. Methods: 149 stroke patients from the Göteborg 70+ Stroke Study were investigated after 18 months. We extracted 4 items corresponding to the NIHSS items on orientation, executive function, language and inattention. Scores on this subset of 4 NIHSS items (Cog-4) and the Mini-Mental State Examination (MMSE) were evaluated against a reference diagnosis of severe cognitive impairment. Results: The area under the receiver-operator curve (AUC) plotted for the Cog-4 scale against the diagnosis of severe cognitive impairment was 0.78; the MMSE had a slightly better diagnostic precision, with an AUC of 0.84. Making the executive task more difficult increased the precision of the Cog-4, raising the AUC to 0.81. Conclusions: A composite score based on 4 NIHSS items is almost as good as the MMSE in detecting severe cognitive impairment. Ideally, dedicated measures of cognition should be employed as a matter of course after stroke, but in their absence, the Cog-4 subscale provides an indication of cognitive functioning.
Cardiovascular Risk and Neuroradiological Profiles in Asymptomatic Vertebrobasilar Dolichoectasia
Authors: Ikeda Ken , Nakamura Yoshikazu , Hirayama Takehisa , Sekine Tokinori , Nagata Riya , Kano Osamu , Kawabe Kiyokazu , Kiyozuka Tetsuhito , Tamura Masaki , Iwasaki Yasuo
Published: April 2010

Background: Clinicoradiological variability of vertebrobasilar dolichoectasia (VBD) is known. Little is known about cardiovascular disease (CVD) risk and neuroradiological profiles of asymptomatic VBD. Methods: A total of 7,345 adults (5,534 men and 1,811 women) underwent physical checkup (PC) and brain magnetic resonance (MR) studies between 2004 and 2007. Asymptomatic VBD was diagnosed by neurological examination and MR angiography. Neuroradiological features were analyzed in VBD subjects. CVD risk factors were compared between VBD subjects and 5,000 controls matched by sex and age. Results: Ninety-six subjects (85 men and 11 women) had asymptomatic VBD. The detection rate was 1.3% and the male/female ratio 2.5. The mean age ± SD was 60.4 ± 10.6 years (60.0 ± 10.2 in men and 64.0 ± 13.1 in women). As compared to controls, the frequency of hypertension, obesity, smoking, dyslipidemia, diabetes mellitus and a family history of stroke or CVD was increased significantly in VBD subjects. The mean diameter ± SD of the basilar artery (BA) was 4.7 ± 0.2 mm. Only 4 subjects (4%) had a severe degree of elongation and lateral displacement of the BA. Contact of the vertebral artery with the rostral ventrolateral medulla (AMC) was found in 81 subjects: right AMC in 22 subjects and left AMC in 59 subjects. Frequency of hypertension was significantly higher in the left-AMC subjects (57%) than in subjects with right AMC (9%) and no AMC (5%). Other neuroradiological findings revealed small infarcts in 42 subjects, brainstem compression in 4, hydrocephalus in 4 and brain saccular aneurysm in 3. Conclusions: Asymptomatic VBD was detected in 1.3% of the Japanese PC group. Our data indicated male predominance, multiple CVD risk factors, neurovascular hypertension and small infarcts in asymptomatic VBD.
Improved Treatment Satisfaction and Convenience with Deferasirox in Iron-Overloaded Patients with β-Thalassemia: Results from the ESCALATOR Trial
Authors: Taher Ali , Al Jefri Abdullah , Elalfy Mohsen Saleh , Al Zir Kusai , Daar Shahina , Rofail Diana , Baladi Jean François , Habr Dany , Kriemler-Krahn Ulrike , El-Beshlawy Amal
Published: April 2010

Patient-reported outcomes of once-daily oral deferasirox (Exjade®) in iron-overloaded patients with β-thalassemia not achieving successful chelation with prior deferoxamine and/or deferiprone were investigated in a prospective, open-label, 1-year, multicenter study in the Middle East (ESCALATOR). The initial dose of deferasirox was 20 mg/kg/day, with subsequent dose adjustments. At baseline and the end of study (EOS), patients (n = 237) completed a 5-point rating scale for treatment satisfaction and convenience, and recorded time lost to treatment. At EOS, 90.7% of patients were ‘satisfied’/‘very satisfied’ with their iron chelation therapy (ICT) versus 23.2% at baseline. 92.8% (EOS) versus 21.5% (baseline) of patients considered their therapy to be ‘convenient’/‘very convenient’. Time lost to therapy for daily activities was substantially reduced (3.2 ± 8.6 [mean ± SD; EOS] vs. 30.1 ± 44.2 [baseline] h/month). Patients reported greater satisfaction and convenience, and lower impact on daily activities, with deferasirox than with previous ICT. This may help improve adherence to lifelong ICT in iron-overloaded β-thalassemia patients.
Systemic Levels of MMP2/TIMP2 and Cardiovascular Risk in CAPD Patients
Authors: Pawlak Krystyna , Tankiewicz Janina , Mysliwiec Michal , Pawlak Dariusz
Published: April 2010

Background/Aims: Matrix metalloproteinases (MMPs), their inhibitors (TIMPs), oxidative stress (SOX) and kynurenine (KYN) pathway have been postulated in cardiovascular disease (CVD) progression. We hypothesized the possible association between the MMP/TIMP system, KYNs and CVD prevalence in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods: We assessed MMP-2, MMP-9, TIMP-1, TIMP-2, KYN and its metabolite – quinolinic acid (QA), and SOX marker – Cu/Zn superoxide dismutase (Cu/Zn SOD) levels in CAPD patients both with and without CVD and healthy controls. Results: MMP-2, TIMP-2, Cu/Zn SOD, KYN and QA were significantly higher in CAPD patients with CVD than in patients without CVD and controls. MMP-2 and TIMP-2 were positively correlated with QA and Cu/Zn SOD levels, and the strong association was between MMP-2 and TIMP-2 levels. Multiple regression analyses identified Cu/Zn SOD, TIMP-2, QA and QA/KYN ratio as the factors independently associated with MMP-2, whereas MMP-2 and Cu/Zn SOD were independent variables affecting TIMP-2 levels. Conclusions: MMP-2 and TIMP-2 concentrations were higher in CAPD patients with CVD than in patients without CVD and healthy controls. Upregulation of the MMP-2/TIMP-2 system was associated with QA levels and increased oxidative status, suggesting the connection between KYN pathway activation, arterial remodeling and CVD prevalence in uremic patients on CAPD treatment.
Meta-Analysis Comparing Sevelamer and Calcium-Based Phosphate Binders on Cardiovascular Calcification in Hemodialysis Patients
Authors: Zhang Qian , Li Ming , Lu Yanwen , Li Haiming , Gu Yong , Hao Chuanming , Chen Jing
Published: April 2010

Background: Accelerated cardiovascular calcification often occurs in patients with cardiovascular disease who are on hemodialysis. We performed a meta-analysis to compare the effects of sevelamer hydrochloride and calcium-based phosphate binders on coronary artery calcification, C-reactive protein, alkaline phosphatase and intact parathyroid hormone in patients undergoing hemodialysis. Methods: We used the key words ‘sevelamer’ and ‘Renagel’ to retrieve studies from Medline, the Cochrane Library and conference proceedings. The trials searched were evaluated for eligibility and quality, and then the data were abstracted and analyzed. Results: We ultimately included 14 studies that enrolled a total of 3,271 patients. There was no difference in coronary artery calcium progression between the calcium and the sevelamer groups. Use of sevelamer, rather than calcium-based phosphate binders, was associated with significantly lower C-reactive protein levels (weighted mean difference (WMD) –1.42; 95% confidence interval (CI) –2.09 to –0.74), higher alkaline phosphatase levels (WMD 22.66; 95% CI 13.81–31.5) and higher intact parathyroid hormone levels (WMD 55.85; 95% CI 14.47–97.24). Conclusions: Treatment with sevelamer did not affect cardiovascular calcification, but there was a trend for lower C-reactive protein levels, higher alkaline phosphatase levels and intact parathyroid hormone levels among sevelamer-treated patients.
Evaluation of Sepsis/Systemic Inflammatory Response Syndrome, Acute Kidney Injury, and RIFLE Criteria in Two Tertiary Hospital Intensive Care Units in Turkey
Authors: Yegenaga Itir , Tuglular Serhan , Ari Elif , Etiler Nilay , Baykara Nur , Torlak Sinan , Acar Sertan , Akbas Turkay , Toker Kamil , Solak Zeynep Mine
Published: April 2010

Sepsis is a common cause of acute renal failure in intensive care units (ICU) with mortality rates as high as 60%. In this study, the clinical and laboratory predictors of acute kidney injury (AKI) in critically ill Turkish patients with sepsis/systemic inflammatory response syndrome were identified. We studied 139 (67 females/72 males) patients admitted to our ICUs with sepsis/systemic inflammatory response syndrome without renal failure. The clinical and laboratory parameters and treatments were recorded. Patients were classified as those without AKI (n = 60; 43.20%) and those with AKI (n = 79; 56.80%) based on the RIFLE (Risk, Injury, Failure, Loss, End-stage renal disease) criteria. Those with AKI were further classified as: risk in 27 (19%), injury in 25 (17.9%), failure in 25 (17.9%), and loss in 2 (1.4%). We found that the mortality rate increased with the severity of renal involvement: 56% in risk, 68% in injury, 72% in failure, and 100% in loss categories. Patients with AKI had a more positive fluid balance, higher central venous pressure, more vasopressor use, and lower systolic blood pressure. In multivariate analysis, the sequential organ failure assessment score, blood pressure, serum creatinine, and fluid balance were risk factors for the development of AKI. In this population, the incidence of AKI was higher and contrary to previous knowledge. A positive fluid balance also carries a risk for AKI and mortality in septic ICU patients. The RIFLE criteria were found to be applicable to our ICU population.
Atypical Chemokine Receptors in Renal Inflammation
Authors: Segerer Stephan , Jedlicka Jan , Wüthrich Rudolf P.
Published: April 2010

Chemokines are structurally related proteins which form a large family of chemotactic cytokines. They provide a general communication system for cells and regulate lymphocyte migration. These proteins orchestrate the formation of microenvironments in lymphoid tissue, promote lymphoid organogenesis and help foster vascular and lymphatic angiogenesis. In addition to the classical G protein-coupled chemokine receptors, many chemokines also bind to a family of nonsignaling proteins, now called interceptors (chemokine-internalizing proteins). Here we summarize recent data on the role of interceptors in chemokine biology with a focus on renal inflammation.
Endogenous Ligands for TLR2 and TLR4 Are Not Involved in Renal Injury following Ureteric Obstruction
Authors: Chowdhury Paramit , Sacks Steven Howard , Sheerin Neil Stephen
Published: April 2010

Background: Toll-like receptors (TLRs) are a recently described arm of innate immunity. As well as responding to conserved molecular patterns found on pathogens, TLRs can also respond to endogenous ligands. Those described for TLR2 and TLR4 include molecules released following tissue injury including heat shock proteins and matrix proteins. We hypothesised that following injury, TLRs on renal tubular cells are activated by these endogenous ligands, resulting in cytokine production and cellular infiltration which propagate the fibrotic process. Methods: We performed unilateral ureteric obstruction (UUO) in wild-type C57BL/6, TLR2 knockout and TLR4 knockout mice. Gene expression of TGF-β and TNF-α within renal tissue was analysed by real-time PCR. Kidneys were also scored for the level of tubulointerstitial fibrosis, collagen type IV deposition and macrophage infiltration. Results: No significant difference was found in the degree of tubulointerstitial fibrosis, collagen type IV deposition or macrophage infiltration 14 days after UUO between the 3 groups. Renal TNF-α and TGF-β gene expression was also similar in all groups 3 days after UUO. Conclusions: TLR2 and TLR4 do not play a significant role in the development of tubulointerstitial fibrosis following obstruction.
Religious Explanatory Models in Patients with Psychosis: A Three-Year Follow-Up Study
Authors: Huguelet P. , Mohr S. , Gilliéron C. , Brandt P.-Y. , Borras L.
Published: April 2010

Background/Aims: Spirituality and religiousness have been shown to be highly prevalent in patients with psychosis. Yet the influence of religious denomination as it affects coping methods and/or as an explanatory model for illness and treatment remains to be determined. This study aims (1) to investigate if religious denomination is associated with explanatory models, (2) to assess the evolution over time of these explanatory models, and (3) to examine the relationship between these explanatory models and the spiritual vision of treatment and adhesion to such treatment. Sampling and Methods: Of an initial cohort of 115 outpatients, 80% (n = 92) participated in a 3-year follow-up study. The evolution of their religious explanatory models was assessed in order to evaluate if religious denomination, as a meaning-making coping tool, is associated with the patients’ explanatory models. Finally, we examined the relationship between these representations and the patients’ spiritual visions of treatment and treatment adhesion. Results: A spiritual vision of the illness (as part of an explanatory model) was more frequent in patients with psychosis for whom the subjective dimension of religion was important. However, there was no association between the patients’ religious denomination and their spiritual vision of the illness. The analyses showed that the various contents of spiritual visions of illness were not positive or negative per se; instead, they depended on how this religious vision was integrated into the person’s experience. Examining longitudinal aspects of coping showed that the spiritual vision sometimes changed, but was not associated with clinical or social outcome. Conclusions: For patients with psychosis, explanatory models frequently involve a religious component which is independent of denomination and likely to change over time. Clinicians should address this issue on a regular basis, by asking patients about their explanatory model before trying to build a bridge with the medical model.
Prevalence of Testicular Microlithiasis in Males with Congenital Adrenal Hyperplasia and Its Association with Testicular Adrenal Rest Tumors
Authors: Poyrazoglu Sukran , Saka Nurcin , Agayev Ayaz , Yekeler Ensar
Published: April 2010

Background: Testicular microlithiasis (TM) is characterized by calcium deposits within the seminiferous tubules and is associated with benign and malign conditions. Aim: To determine TM prevalence in patients with congenital adrenal hyperplasia (CAH) and its association with testicular adrenal rest tumors (TART). Patients and Methods: Scrotal ultrasound using a high-frequency linear transducer (12 MHz) was performed in 41 patients aged 12.1 ± 4.7 (range 3.5–23.3) years and 49 healthy similarly aged controls. TM was classified with respect to the number of microliths per ultrasound field as limited (LTM, <5 microliths) and classic (CTM, ≧ 5 microliths). CTM was graded as grade 1 (5–10 microliths), grade 2 (11–20 microliths), and grade 3 (>20 microliths). Results: TM was detected bilaterally in 9 (21.9%) patients and 2 (4.1%) control cases (1 bilateral, 1 unilateral). Four patients had LTM, one evaluated as grade 1, one as grade 2, and three as grade 3. There were 9 patients with TART. Four patients had TM and TART concomitantly. Conclusion: Because TM is frequently found in patients with CAH and may also exist concomitantly with TART, we recommend that these patients be followed annually by testicular ultrasound.
Screening of Genital Anomalies in Newborns and Infants in Two Egyptian Governorates
Authors: Mazen I. , El-Ruby M. , Kamal R. , El-Nekhely I. , El-Ghandour M. , Tantawy S. , El-Gammal M.
Published: April 2010

Background: External genital anomalies are among the most common congenital anomalies. Proper early diagnosis and management of genital abnormalities are of great importance to minimize medical, psychological and social complications. Aim: To detect the incidence of external genital anomalies and disorders of sex development (DSD) in Great Cairo and Qalyubiyah governorates. Subjects and Methods: 20,000 newborns and infants up to the age of 6 months coming for compulsory vaccination at primary health care units and centers in Great Cairo and Qalyubiyah governorates were examined in the years 2006–2007 for suspected genital anomalies. Results: There were 187 (93.5/10,000) cases with external genital anomalies among the screened 20,000 participants. Various abnormalities in the form of 46,XY DSD, undescended testis, hydrocele, hypospadias, micropenis, synechia of the labia and other genital anomalies were diagnosed and classified after thorough clinical examination, and hormonal, radiological, and laparoscopic investigations. Conclusion: This first pilot study in Great Cairo and Qalyubiyah governorates showed a relatively high incidence of genital anomalies and DSD. Therefore, we recommend more studies including larger population sizes to detect the actual incidence of genital anomalies and DSD in Egypt in order to serve those patients and their families.
Fiberoptic Bronchoscopy during Nasal Non-Invasive Ventilation in Acute Respiratory Failure
Authors: Chiner E. , Sancho-Chust J.N. , Llombart M. , Senent C. , Camarasa A. , Signes-Costa J.
Published: April 2010

Background: Various methods have been described for safely performing fiberoptic bronchoscopy (FB) while applying non-invasive positive pressure ventilation (NIPPV) in patients with acute respiratory failure (ARF). Objectives: To evaluate the safety of a new method to perform FB in patients with ARF. Methods: Patients with ARF in whom FB was indicated were studied. The primary end-point was a mean drop in oxygen saturation (SaO2) after the procedure. During nasal NIPPV, FB was performed via the mouth using a bite block sealed with an elastic glove finger allowing bronchoscope insertion. Results: Thirty-five patients were included in the final study (63 ± 17 years, 74% men, PaO2/FiO2 ratio 168 ± 63). A total of 35 bronchoaspirates, 21 protected brushings, 11 bronchoalveolar lavages and 8 bronchial biopsies were done. The cardiorespiratory variables at the start and end of FB were: SaO2 93 ± 3 to 94 ± 5%, heart rate 95 ± 17 to 99 ± 22 b.p.m. and respiratory rate 24 ± 11 to 25 ± 11 respirations/min. The lowest SaO2 value reached during the procedure was 86 ± 3% and the maximal ETCO2 rise was 41 ± 4 mm Hg. Leakage was <50 ml/s in 32 patients. The clinical course was favorable in 66%. Invasive ventilation was necessary in 11%, 5 ± 4 days after FB. Twelve patients (33%) died 3 ± 2 days after FB as a result of their underlying disease. Conclusions: The system allowed to perform FB safely in patients with ARF. Although there is a relatively high rate of intubation and invasive mechanical ventilation due to illness severity, there was no worsening of oxygenation or complications attributable to the procedure.
Global Hybrid Public-Private Bodies: The World Anti-Doping Agency (WADA)
Authors: Casini Lorenzo
Published: April 2010

Acting in concert, States, sporting institutions and members of the international community have created a body that is emblematic of the emergence of the new forms of hybrid public-private governance mechanisms in the global sphere: the World Anti-Doping Agency (WADA). This article examines the structure and activities of this institution, in order to highlight a number of problems concerning the increasing use of public-private partnerships (PPPs) at the global level: the spread of normative functions carried out by global institutions and the binding force of these norms; the harmonization of different regulations at the global level; and the adoption of administrative law type mechanisms within global regimes and the emergence of global administrative law.
Holocene soils and sediments around Ma’rib Oasis, Yemen: Further Sabaean treasures?
Authors: Pietsch Dana , Kühn Peter , Scholten Thomas , Brunner Ueli , Hitgen Holger , Gerlach Iris
Published: April 2010

The ancient cultures of Southern Arabia are increasingly recognised as playing as major a role in the heritage of mankind as the early cultures of Egypt, Mesopotamia or the Indus Valley. The beginning of the widely known Sabaean culture dates back to the end of the second millennium BC. Whereas, undoubtedly, its wealth came mainly from the trade along the Incense Road, the backbone of its economy was irrigated agriculture. Since agriculture is based on soil and water resources and, hence, land availability, the buried soils and sediments of the area surrounding the Ma’rib Oasis have been investigated, both as an archive of Holocene soil development in Pre-Sabaean times and as ‘natural treasures’, as, for example, ores or alabaster are defined. The natural buried Holocene soils around Ma’rib are rich in phosphate, organic material and volcanic ashes. In a few places they demonstrate cultivation before the Great Dam of Ma’rib was built in the first millennium BC. Most important are those soils that formed during the Neolithic between 8000 and 3000 BC, a time before the permanent settlement of humans in the Bronze Age, and before the arrival of those of the early Sabaean period at the Ar-Rub’ Al-Khali desert margin. Since the area surrounding the oasis shows a huge variety of landscapes, such as dune belts, volcanic fields with archaeological structures and different soils, it is worth accentuating the significance of Holocene soils as an important record or archive of land use. As well as classical soil analysis, AMS- 14C-datings, the results of phytolith analysis and geochemistry, including XRF data, have been taken into consideration.
An Analysis between Implied and Realised Volatility in the Greek Derivative Market
Authors: Filis George
Published: April 2010

In this article, we examine the relationship between implied and realised volatility in the Greek derivative market. We examine the differences between realised volatility and implied volatility of call and put options for at-the-money index options with a two-month expiration period. The findings provide evidence that implied volatility is not an efficient estimate of realised volatility. Implied volatility creates overpricing, for both call and put options, in the Greek market. This is an indication of inefficiency for the market. In addition, we find evidence that realised volatility ‘Granger causes’ implied volatility for call options, and implied volatility of call options ‘Granger causes’, the implied volatility of put options.
Child ADHD Severity and Positive and Negative Parenting as Predictors of Child Social Functioning: Evaluation of Three Theoretical Models
Authors: Kaiser Nina M. , McBurnett Keith , Pfiffner Linda J.
Published: April 2010

Objective: Prior research has established links between child social functioning and both parenting and child ADHD severity; however, research examining the way that these variables work together is lacking. The current article aims to test three possible models (main effects, mediation, and moderation) by which ADHD severity and positive and negative parenting on the part of both mothers and fathers may work together to predict child social functioning. Method: In a combined sample of children ages 5 to 11 with and without ADHD ( N = 143), multiple regression was used to assess: (a) the main effects of ADHD severity and of positive and negative parenting by both mothers and fathers on child social skill and aggressive behavior; (b) parenting as a potential mediator of the relation between ADHD severity and child social skill and aggressive behavior; and (c) ADHD severity as a potential moderator of the relation between parenting and child social skill and aggressive behavior dependent variables. Results: Significant main effects of both ADHD severity and parenting on child social skill and aggression were found. There was some evidence to support parenting (particularly negative parenting) as a mediator of the relation between ADHD severity and child social skill and aggression. There was no evidence of significant moderational effects. Conclusion: Parenting and ADHD severity are independently associated with child social skill and aggressive behavior.To the extent that these associations are causal, multimodal treatment targeting both symptom reduction and improved parenting may be especially effective for the treatment of social problems related to childhood ADHD. Furthermore, evidence for parenting as a mediator of the relation between ADHD severity and child outcomes suggests that changes in child symptoms may also improve parenting practices, thus leading to improved child outcomes. ( J. of Att. Dis. 2011; 15(3) 193-203)
Italian Television in the Multichannel Age
Authors: D'Arma Alessandro
Published: April 2010

It is only in the last few years that multichannel television has really made inroads in Italy. This article assesses the nature and extent of change that has taken place in Italian television in the move from a handful of terrestrial channels to hundreds of digital channels. It considers emerging trends in terms of ownership, revenue models, programming and consumption. It is argued that Italian television has undergone substantial change in recent years, the rise of News Corporation’s Sky Italia and the growing centrality of pay-TV to the economics of the industry being the main novelties. However, there are also important elements of continuity. Mediaset and RAI’s established terrestrial channels remain the only truly mass-audience media in Italy. Judging from current viewing patterns and in light of regulatory conditions and economic considerations, they are likely to remain so even in the all-digital scenario of the near future. In the longer term, however, fundamental change may also occur at this level, the analysis pointing in particular to the risk for public broadcaster RAI to become increasingly marginal in future, given the political and economic constraints it currently faces.
Negotiating treatment for hepatitis C: Interpersonal alignment in the clinical encounter
Authors: Körner Henrike
Published: April 2010

Antiviral treatment for hepatitis C constitutes a considerable physical and psycho-social challenge without guarantee of treatment success. Using semi-structured in-depth interviews, this article investigates the experiences of people on hepatitis C treatment and the experiences of physicians who care for people with hepatitis C. Given the importance of the interpersonal dimension of the patient—physician relationship for patients accessing treatment, adhering to treatment, dealing with treatment side-effects and completing treatment, the article focuses on the interpersonal dimension of patients’ and physicians’ accounts. The theoretical foundation is ‘appraisal’ theory from systemic functional linguistics, which is grounded in Bakhtin’s notions of heteroglossia and dialogism. The article describes the intersubjective stances that patients and physicians adopt in accounts of their interactions about hepatitis C treatment, the values they construct and the semantic backdrop against which these meanings are constructed. The article traces the semantic patterns of intersubjective alignment and disalignment between patients and physicians, as well as the semantics of patients’ challenging the intersubjective stances taken by their physicians. While the biomedical discourse was intersubjectively at odds with the experiences of some patients, others aligned with it. In fact, understanding and speaking the language of biomedicine enabled some patients to challenge the traditional doctor—patient relationship and to reconfigure it into a partnership approach.