bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced glycogen metabolism in adipose tissue decreases triglyceride mobilization
Authors: Markan Kathleen R. , Jurczak Michael J. , Allison Margaret B. , Ye Honggang , Sutanto Maria M. , Cohen Ronald N. , Brady Matthew J.
Published: April 2010

Adipose tissue is a primary site for lipid storage containing trace amounts of glycogen. However, refeeding after a prolonged partial fast produces a marked transient spike in adipose glycogen, which dissipates in coordination with the initiation of lipid resynthesis. To further study the potential interplay between glycogen and lipid metabolism in adipose tissue, the aP2-PTG transgenic mouse line was utilized since it contains a 100- to 400-fold elevation of adipocyte glycogen levels that are mobilized upon fasting. To determine the fate of the released glucose 1-phosphate, a series of metabolic measurements were made. Basal and isoproterenol-stimulated lactate production in vitro was significantly increased in adipose tissue from transgenic animals. In parallel, basal and isoproterenol-induced release of nonesterified fatty acids (NEFAs) was significantly reduced in transgenic adipose tissue vs. control. Interestingly, glycerol release was unchanged between the genotypes, suggesting that enhanced triglyceride resynthesis was occurring in the transgenic tissue. Qualitatively similar results for NEFA and glycerol levels between wild-type and transgenic animals were obtained in vivo during fasting. Additionally, the physiological upregulation of the phospho enolpyruvate carboxykinase cytosolic isoform (PEPCK-C) expression in adipose upon fasting was significantly blunted in transgenic mice. No changes in whole body metabolism were detected through indirect calorimetry. Yet weight loss following a weight gain/loss protocol was significantly impeded in the transgenic animals, indicating a further impairment in triglyceride mobilization. Cumulatively, these results support the notion that the adipocyte possesses a set point for glycogen, which is altered in response to nutritional cues, enabling the coordination of adipose glycogen turnover with lipid metabolism.
Curve-based multivariate distance matrix regression analysis: application to genetic association analyses involving repeated measures
Authors: Salem Rany M. , O'Connor Daniel T. , Schork Nicholas J.
Published: April 2010

Most, if not all, human phenotypes exhibit a temporal, dosage-dependent, or age effect. Despite this fact, it is rare that data are collected over time or in sequence in relevant studies of the determinants of these phenotypes. The costs and organizational sophistication necessary to collect repeated measurements or longitudinal data for a given phenotype are clearly impediments to this, but greater efforts in this area are needed if insights into human phenotypic expression are to be obtained. Appropriate data analysis methods for genetic association studies involving repeated or longitudinal measures are also needed. We consider the use of longitudinal profiles obtained from fitted functions on repeated data collections from a set of individuals whose similarities are contrasted between sets of individuals with different genotypes to test hypotheses about genetic influences on time-dependent phenotype expression. The proposed approach can accommodate uncertainty of the fitted functions, as well as weighting factors across the time points, and is easily extended to a wide variety of complex analysis settings. We showcase the proposed approach with data from a clinical study investigating human blood vessel response to tyramine. We also compare the proposed approach with standard analytic procedures and investigate its robustness and power via simulation studies. The proposed approach is found to be quite flexible and performs either as well or better than traditional statistical methods.
Niobium Uptake and Release by Bacterial Ferric Ion Binding Protein
Authors: Shi Yanbo , Harvey Ian , Campopiano Dominic , Sadler Peter J.
Published: April 2010

Ferric ion binding proteins (Fbps) transport FeIII across the periplasm and are vital for the virulence of many Gram negative bacteria. Iron(III) is tightly bound in a hinged binding cleft with octahedral coordination geometry involving binding to protein side chains (including tyrosinate residues) together with a synergistic anion such as phosphate. Niobium compounds are of interest for their potential biological activity, which has been little explored. We have studied the binding of cyclopentadienyl and nitrilotriacetato NbV complexes to the Fbp from Neisseria gonorrhoeae by UV‐vis spectroscopy, chromatography, ICP‐OES, mass spectrometry, and Nb K‐edge X‐ray absorption spectroscopy. These data suggest that NbV binds strongly to Fbp and that a dinuclear NbV centre can be readily accommodated in the interdomain binding cleft. The possibility of designing niobium‐based antibiotics which block iron uptake by pathogenic bacteria is discussed.
An Approach for Implementing State Machines with Online Testability
Authors: Lala P. K. , Mathews A. , Parkerson J. P.
Published: April 2010

During the last two decades, significant amount of research has been performed to simplify the detection of transient or soft errors in VLSI-based digital systems. This paper proposes an approach for implementing state machines that uses 2-hot code for state encoding. State machines designed using this approach allow online detection of soft errors in registers and output logic. The 2-hot code considerably reduces the number of required flip-flops and leads to relatively straightforward implementation of next state and output logic. A new way of designing output logic for online fault detection has also been presented.
The Abandoned Radical Hysterectomy for Cervical Cancer: Clinical Predictors and Outcomes
Authors: Gray Heidi J. , Seifert Erin , Sal y Rosas Victor G. , Nicandri Katrina F. , Koh Wui-Jin , Goff Barbara A.
Published: April 2010

Objective. Cervical cancer patients who had an abandoned radical hysterectomy were evaluated for preoperative clinical predictors, complication rates, and outcomes. Study Design. IRB approval was obtained for this retrospective analysis and chart review was performed. Results. From 268 women with early‐stage (IA2 to IIA) cervical cancer, 19 (7%) had an abandoned hysterectomy for finding grossly positive lymph nodes (84%) or pelvic spread of tumor (16%). No clinical characteristics clearly identified women preoperatively at risk of having an abandoned hysterectomy. In the abandoned group, 26% suffered major morbidities, compared to 34% in the completed group (OR 0.69, [CI 0.16–2.57], P = .789). Thirty‐seven percent recurred in the abandoned group, compared to 18% in the completed group (P = .168). Overall survival in the abandoned group was 73% versus 80% in the completed group (P = .772). Conclusion. The practice of abandoning a planned radical hysterectomy for unexpected metastatic disease may not worsen the outcome.
Role of H2O2 in RET/PTC1 Chromosomal Rearrangement Produced by Ionizing Radiation in Human Thyroid Cells
Authors: Ameziane-El-Hassani Rabii , Boufraqech Myriem , Lagente-Chevallier Odile , Weyemi Urbain , Talbot Monique , Métivier Didier , Courtin Françoise , Bidart Jean-Michel , El Mzibri Mohammed , Schlumberger Martin , Dupuy Corinne
Published: April 2010

During childhood, the thyroid gland is one of the most sensitive organs to the carcinogenetic effects of ionizing radiation that may lead to papillary thyroid carcinoma (PTC) associated with RET/PTC oncogene rearrangement. Exposure to ionizing radiation induces a transient “oxidative burst” through radiolysis of water, which can cause DNA damage and mediates part of the radiation effects. H2O2 is a potent DNA-damaging agent that induces DNA double-strand breaks, and consequently, chromosomal aberrations. Irradiation by 5 Gy X-ray increased extracellular H2O2. Therefore, we investigated the implication of H2O2 in the generation of RET/PTC1 rearrangement after X-ray exposure. We developed a highly specific and sensitive nested reverse transcription-PCR method. By using the human thyroid cell line HTori-3, previously found to produce RET/PTC1 after γ-irradiation, we showed that H2O2, generated during a 5 Gy X-ray irradiation, causes DNA double-strand breaks and contributes to RET/PTC1 formation. Pretreatment of cells with catalase, a scavenger of H2O2, significantly decreased RET/PTC1 rearrangement formation. Finally, RET/PTC chromosomal rearrangement was detected in HTori-3.1 cells after exposure of cells to H2O2 (25 μmol/L), at a dose that did not affect the cell viability. This study shows for the first time that H2O2 is able to cause RET/PTC1 rearrangement in thyroid cells and consequently highlights that oxidative stress could be responsible for the occurrence of RET/PTC1 rearrangement found in thyroid lesions even in the absence of radiation exposure. Cancer Res; 70(10); 4123–32. ©2010 AACR.
Epidermal Growth Factor Receptor and Mutant p53 Expand an Esophageal Cellular Subpopulation Capable of Epithelial-to-Mesenchymal Transition through ZEB Transcription Factors
Authors: Ohashi Shinya , Natsuizaka Mitsuteru , Wong Gabrielle S. , Michaylira Carmen Z. , Grugan Katharine D. , Stairs Douglas B. , Kalabis Jiri , Vega Maria E. , Kalman Ross A. , Nakagawa Momo , Klein-Szanto Andres J. , Herlyn Meenhard , Diehl J. Alan , Rustgi Anil K. , Nakagawa Hiroshi
Published: April 2010

Transforming growth factor-β (TGF-β) is a potent inducer of epithelial to mesenchymal transition (EMT). However, it remains elusive about which molecular mechanisms determine the cellular capacity to undergo EMT in response to TGF-β. We have found that both epidermal growth factor receptor (EGFR) overexpression and mutant p53 tumor suppressor genes contribute to the enrichment of an EMT-competent cellular subpopulation among telomerase-immortalized human esophageal epithelial cells during malignant transformation. EGFR overexpression triggers oncogene-induced senescence, accompanied by the induction of cyclin-dependent kinase inhibitors p15INK4B, p16INK4A, and p21. Interestingly, a subpopulation of cells emerges by negating senescence without loss of EGFR overexpression. Such cell populations express increased levels of zinc finger E-box binding (ZEB) transcription factors ZEB1 and ZEB2, and undergo EMT on TGF-β stimulation. Enrichment of EMT-competent cells was more evident in the presence of p53 mutation, which diminished EGFR-induced senescence. RNA interference directed against ZEB resulted in the induction of p15INK4B and p16INK4A, reactivating the EGFR-dependent senescence program. Importantly, TGF-β–mediated EMT did not take place when cellular senescence programs were activated by either ZEB knockdown or the activation of wild-type p53 function. Thus, senescence checkpoint functions activated by EGFR and p53 may be evaded through the induction of ZEB, thereby allowing the expansion of an EMT-competent unique cellular subpopulation, providing novel mechanistic insights into the role of ZEB in esophageal carcinogenesis. Cancer Res; 70(10); 4174–84. ©2010 AACR.
Intravital Imaging Illuminates Transforming Growth Factor β Signaling Switches during Metastasis
Authors: Giampieri Silvia , Pinner Sophie , Sahai Erik
Published: April 2010

Transforming growth factor β (TGFβ) has seemingly contradictory roles in tumor progression: it can promote metastatic invasion but also act as a tumor suppressor. Recently, two studies have used intravital imaging to unravel the role of TGFβ at different stages of the metastatic process. TGFβ promotes single cell motility, which enables invasion into blood vessels. However the activation of TGFβ signaling is a transient event and is not maintained at distant sites. The downregulation of TGFβ signaling at secondary sites then permits growth of secondary tumors. In the absence of TGFβ, cells are restricted to collective movement and lymphatic spread. Here, we discuss these findings and their potential implications. Cancer Res; 70(9); 3435–9. ©2010 AACR.
New Strategies in Prostate Cancer: Targeting Lipogenic Pathways and the Energy Sensor AMPK
Authors: Zadra Giorgia , Priolo Carmen , Patnaik Akash , Loda Massimo
Published: April 2010

Although the role of metabolic syndrome (MS) and a high fat diet in prostate cancer (PCa) risk is still a matter of intense debate, it is becoming increasingly clear that obesity can cause perturbations in metabolic pathways that contribute to the pathogenesis and progression of PCa. Moreover, prostate epithelial cells per se undergo a series of metabolic changes, including an increase in de novo lipogenesis, during the process of tumor formation. These metabolic alterations, at both the cellular and organismal levels, are intertwined with genetic aberrations necessary for neoplastic transformation. Thus, altered metabolism is currently subject to intense research efforts and might provide preventative and therapeutic opportunities, as well as a platform for biomarker development. In this article, we review evidence that the metabolic sensor 5′-AMP-activated protein kinase (AMPK), which physiologically integrates nutritional and hormonal signals and regulates cell survival and growth-related metabolic pathways to preserve intracellular ATP levels, represents a link between energy homeostasis and cancer. Thus, when AMPK is not activated, as in the setting of MS and obesity, systemic metabolic alterations permissive to the development of PCa are allowed to proceed unchecked. Hence, the use of AMPK activators and inhibitors of key lipogenic enzymes may represent a promising therapeutic strategy for PCa. Clin Cancer Res; 16(13); 3322–8. ©2010 AACR.
Inhibition of Fatty Acid Synthase Suppresses c-Met Receptor Kinase and Induces Apoptosis in Diffuse Large B-Cell Lymphoma
Authors: Uddin Shahab , Hussain Azhar R. , Ahmed Maqbool , Bu Rong , Ahmed Saeeda O. , Ajarim Dahish , Al-Dayel Fouad , Bavi Prashant , Al-Kuraya Khawla S.
Published: April 2010

Fatty acid synthase (FASN), the enzyme responsible for de novo synthesis of fatty acids, has emerged as a potential therapeutic target for several cancers; however, its role in diffuse large B-cell lymphoma (DLBCL) has not been fully elucidated. In this study, we investigated the role of FASN in a large series of DLBCL tissues in a tissue microarray (TMA) format followed by in vitro studies using DLBCL cell lines. FASN was found to be expressed in 62.6% DLBCL samples and was seen in highly proliferative tumors, manifested by high Ki67 (P < 0.0001). Significant association was found between tumors expressing high FASN and c-Met tyrosine kinase (P < 0.0002), as well as p-AKT (P = 0.0309). In vitro, pharmacological FASN inhibition and small interference RNA (siRNA) targeted against FASN triggered caspase-dependent apoptosis and suppressed expression of c-Met kinase in DLBCL cell lines, which further highlighted the molecular link between FASN and c-Met kinase. Finally, simultaneous targeting of FASN and c-Met with specific chemical inhibitors induced a synergistically stimulated apoptotic response in DLBCL cell lines. These findings provide evidence that FASN, via c-Met tyrosine kinase, plays a critical role in the carcinogenesis of DLBCL and strongly suggest that targeting FASN may have therapeutic value in treatment of DLBCL. Mol Cancer Ther; 9(5); 1244–55. ©2010 AACR.
Epigallocatechin Gallate Suppresses Lung Cancer Cell Growth through Ras–GTPase-Activating Protein SH3 Domain-Binding Protein 1
Authors: Shim Jung-Hyun , Su Zheng-Yuan , Chae Jung-Il , Kim Dong Joon , Zhu Feng , Ma Wei-Ya , Bode Ann M. , Yang Chung S. , Dong Zigang
Published: April 2010

Green tea is a highly popular beverage globally. Green tea contains a number of polyphenol compounds referred to as catechins, and (−)-epigallocatechin gallate (EGCG) is believed to be the major biologically active compound found in green tea. EGCG has been reported to suppress lung cancer, but the molecular mechanisms of the inhibitory effects of EGCG are not clear. We found that EGCG interacted with the Ras–GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) with high binding affinity (Kd = 0.4 μmol/L). We also showed that EGCG suppressed anchorage-independent growth of H1299 and CL13 lung cancer cells, which contain an abundance of the G3BP1 protein. EGCG was much less effective in suppressing anchorage-independent growth of H460 lung cancer cells, which express much lower levels of G3BP1. Knockdown shG3BP1-transfected H1299 cells exhibited substantially decreased proliferation and anchorage-independent growth. shG3BP1 H1299 cells were resistant to the inhibitory effects of EGCG on growth and colony formation compared with shMock-transfected H1299 cells. EGCG interfered with the interaction of G3BP1 and the Ras–GTPase-activating protein and further suppressed the activation of Ras. Additional results revealed that EGCG effectively attenuated G3BP1 downstream signaling, including extracellular signal-regulated kinase and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase, in wild-type H1299 and shMock H1299 cells but had little effect on H460 or shG3BP1 H1299 cells. Overall, these results strongly indicate that EGCG suppresses lung tumorigenesis through its binding with G3BP1. Cancer Prev Res; 3(5); 670–9. ©2010 AACR.
Is Prostate Cancer Prevention with Selenium All in the Genes?
Authors: Platz Elizabeth A.
Published: April 2010

This perspective discusses how well-conducted research by Penney et al. (beginning on page 604 in this issue of the journal) contributes to the incremental uncovering of the complex association between selenium and prostate cancer. These investigators' earlier findings and current questions, approaches, and findings regarding selenium for prostate cancer prevention are discussed. This group's work raises the following important inferences: Selenium may prevent poorer-prognosis prostate cancer and its progression to bony metastases and death, but only in men with genetic backgrounds that influence the requirement for selenium. These inferences point toward how to reconcile inconsistent prostate cancer risk results from the two randomized trials of selenium conducted to date. Cancer Prev Res; 3(5); 576–8. ©2010 AACR.
Studies of Chinese Speakers with Dysarthria: Informing Theoretical Models
Authors: Whitehill Tara L.
Published: April 2010

Most theoretical models of dysarthria have been developed based on research using individuals speaking English or other Indo-European languages. Studies of individuals with dysarthria speaking other languages can allow investigation into the universality of such models, and the interplay between language-specific and language-universal aspects of dysarthria. In this article, studies of Cantonese- and Mandarin-Chinese speakers with dysarthria are reviewed. The studies focused on 2 groups of speakers: those with cerebral palsy and those with Parkinson’s disease. Key findings are compared with similar studies of English speakers. Since Chinese is tonal in nature, the impact of dysarthria on lexical tone has received considerable attention in the literature. The relationship between tone [which involves fundamental frequency (F₀) control at the syllable level] and intonation (involving F₀ control at the sentential level) has received more recent attention. Many findings for Chinese speakers with dysarthria support earlier findings for English speakers, thus affirming the language-universal aspect of dysarthria. However, certain differences, which can be attributed to the distinct phonologies of Cantonese and Mandarin, highlight the language-specific aspects of the condition.
Short-Term Effects of Repetitive Transcranial Magnetic Stimulation on Speech and Voice in Individuals with Parkinson’s Disease
Authors: Hartelius L. , Svantesson P. , Hedlund A. , Holmberg B. , Revesz D. , Thorlin T.
Published: April 2010

The main characteristics of dysarthria in Parkinson’s disease (PD) are monotony of pitch and loudness, reduced stress, variable speech rate, imprecise consonants, and breathy and harsh voice. Earlier treatment studies have shown that dysarthria is less responsive to both pharmacological and surgical treatments than other gross motor symptoms. Recent findings have suggested that repetitive transcranial magnetic stimulation (rTMS) may have a beneficial effect on vocal function in PD. In the present study, 10 individuals with mild PD and no or minimal dysarthria were treated with rTMS as well as placebo stimulation in a blinded experiment. Stimulation was delivered using a frequency of 10 Hz and a stimulation intensity of 90% of the motor threshold. The site of stimulation was the cortical area corresponding to the hand, on the hemisphere contralateral to the patient’s most affected side. The participants were audio-recorded before and after both rTMS and sham stimulation. Acoustic analysis was performed on 3 sustained /a:/ for each of the 4 conditions, and analyzed both for the whole group as well as for men and women separately. Results showed that there were no significant differences between any of the conditions regarding duration of sustained fricative or sustained vowel phonation, diadochokinetic rates or intelligibility. Above all, the results of acoustic analyses showed an effect of placebo; there was a significant reduction in fundamental frequency (F₀) variation, pitch period perturbation, amplitude period perturbation, noise-to-harmonics ratio and coefficient of variation in F₀ between the recordings performed before compared to after sham stimulation.
Chromosomal Evolution in the Brazilian Geckos of the Genus Gymnodactylus (Squamata, Phyllodactylidae) from the Biomes of Cerrado, Caatinga and Atlantic Rain Forest: Evidence of Robertsonian Fusion Events and Supernumerary Chromosomes
Authors: Pellegrino K.C.M. , dos Santos R.M.L. , Rodrigues M.T. , Laguna M.M. , Amaro R.C. , Yonenaga-Yassuda Y.
Published: April 2010

Chromosomes of the South American geckos Gymnodactylus amarali and G. geckoides from open and dry areas of the Cerrado and Caatinga biomes in Brazil, respectively, were studied for the first time, after conventional and AgNOR staining, CBG- and RBG-banding, and FISH with telomeric sequences. Comparative analyses between the karyotypes of open areas and the previously studied Atlantic forest species G. darwinii were also performed. The chromosomal polymorphisms detected in populations of G. amarali from the states of Goiás and Tocantins is the result of centric fusions (2n = 38, 39 and 40), suggesting a differentiation from a 2n = 40 ancestral karyotype and the presence of supernumerary chromosomes. The CBG- and RBG-banding patterns of the Bs are described. G. geckoides has 40 chromosomes with gradually decreasing sizes, but it is distinct from the 2n = 40 karyotypes of G. amarali and G. darwinii due to occurrence of pericentric inversions or centromere repositioning. NOR location seems to be a marker for Gymnodactylus, as G. amarali and G. geckoides share a medium-sized subtelocentric NOR-bearing pair, while G. darwinii has NORs at the secondary constriction of the long arm of pair 1. The comparative analyses indicate a non-random nature of the Robertsonian rearrangements in the genus Gymnodactylus.
Origin and Evolution of Parthenogenetic Genomes in Lizards: Current State and Future Directions
Authors: Fujita M.K. , Moritz C.
Published: April 2010

The atypical characteristics of parthenogenetic lizards offer a rare glimpse into the evolution of asexual vertebrate genomes, addressing the genetic consequences of 2 major hypotheses regarding the absence of sex: reduced potential for adaptation and the accumulation of deleterious mutations. As a consequence of their hybrid origin, parthenogenetic lizards exhibit admixed genomes that offer opportunities to study functional genomics and the disruption of coevolved gene complexes in a potentially perpetual hybrid background. The high heterozygosity also provides substantial signal to track instances of fundamental genomic processes, such as intergenomic recombination, transcriptional silencing, and mutation. The mitochondrial genomes of parthenogenetic lizards have unveiled evidence for both slipped-strand mispairing and unconventional initiation/termination of DNA replication as mechanisms generating large, tandem duplications that are fleeting in sexual animals, as well as a rare glimpse into the intermediate steps of the duplication-random loss model of mitochondrial gene rearrangement. Several important questions remain, for instance, how do polyploid, and in particular triploid, lineages solve issues of genome dosage? What are the molecular bases of meiosis and development that enable parthenogenesis? Expanding the synergy between natural history research and molecular biology promises to address these unanswered questions. Advances in methodology (such as genomic in situ hybridization) as well as high-throughput genome and transcriptome sequencing offer new opportunities to explore the persistent questions regarding asexual genome evolution with great precision.
Risk of Aneurysm Rupture at Intracranial Arterial Bifurcations
Authors: van der Kolk Nicolien M. , Algra Ale , Rinkel Gabrië‘l J.E.
Published: April 2010

Background: Aneurysms on the posterior circulation, most commonly located at the basilar top, have a higher risk of rupture than aneurysms on the anterior circulation. If hemodynamic shear stress, which has its maximum impact at the distal carina of bifurcations, explains the higher rupture rate of basilar top aneurysms, aneurysms at the top of the carotid artery should have similar rupture rates given their geometrical similarities. Aim: Our purpose was to compare rupture risks of carotid and basilar artery bifurcation aneurysms. Methods: We included studies from Medline and Embase searches and compared proportions of ruptured and unruptured aneurysms at the basilar and carotid bifurcation with the assumption that carotid aneurysms are twice as prevalent based on the presence of 2 carotid and 1 basilar artery bifurcation on the circle of Willis. Results: Of all unruptured aneurysms, 8.3% were located on the basilar and 6.0% on the carotid bifurcation; 8.0% of all ruptured aneurysms were located on the basilar and 4.3% on the carotid bifurcation. Subsequently the ratios of carotid versus basilar aneurysms were 0.72 for unruptured and 0.55 for ruptured aneurysms, instead of the expected 2.0. Conclusions: Aneurysms are less frequently located on the carotid than on the basilar artery bifurcation. The proportion of ruptured carotid aneurysms is smaller than that of unruptured carotid aneurysms, suggesting a lower rupture risk for aneurysms at the carotid artery bifurcation. The anatomical geometry of the bifurcations and concomitant hemodynamic stress are considered an unlikely explanation for the higher risk of posterior circulation aneurysms.
Spherical Carbon Adsorbent (AST-120) Protects Deterioration of Renal Function in Chronic Kidney Disease Rats through Inhibition of Reactive Oxygen Species Production from Mitochondria and Reduction of Serum Lipid Peroxidation
Authors: Owada Shigeru , Maeba Teruhiko , Sugano Yasuji , Hirayama Aki , Ueda Atsushi , Nagase Sohji , Goto Sumie , Nishijima Fuyuhiko , Bannai Kenji , Yamato Hideyuki
Published: April 2010

Background/Aim: An imbalance in renal redox status contributes to progression of renal dysfunction. We investigated the effects of an oral charcoal adsorbent (AST-120) on renal redox status, superoxide production from renal mitochondria, and serum lipid peroxidation using chronic kidney disease (CKD) model rats. Methods: CKD was induced by 5/6 nephrectomy. CKD rats were divided into 2 groups: controls, and those treated with AST-120 for 20 weeks. We evaluated: (1) renal redox status by in vivo low-frequency electron spin resonance imaging (EPRI); (2) renal superoxide scavenging activity (SSA); (3) superoxide production from renal mitochondria; (4) immunostaining for Cu-Zn superoxide dismutase (SOD), and (5) oxidative stress markers including LDL-negative charge (LDL-CMF), serum lipid peroxide (LPO) and urinary hexanoyl-lysine (HEL). The effect of indoxyl sulfate, a uremic toxin, on mitochondrial superoxide production was also investigated. Results: AST-120 treatment improved renal function, renal SSA, renal mitochondrial superoxide production, renal SOD expression, renal redox status by EPRI, and oxidative stress profiles by LDL-CMF, LPO and urinary HEL. Addition of indoxyl sulfate increased mitochondrial superoxide production and AST-120 also decreased this. Conclusions: Improvements in the redox status and lipid peroxidation induced by AST-120 may delay the progression of CKD.
Non-Verbal Behaviour of Patients with Schizophrenia in Medical Consultations – A Comparison with Depressed Patients and Association with Symptom Levels
Authors: Dimic Sara , Wildgrube Christiane , McCabe Rosemarie , Hassan Imren , Barnes Thomas R.E. , Priebe Stefan
Published: April 2010

Background: The Dutch psychiatrist Rümke introduced the notion that patients with schizophrenia could be recognised intuitively by an experienced psychiatrist, naming the process as the ‘praecox feeling’. This feeling may reflect aspects of the non-verbal behaviour of patients as shown in a medical consultation. The aim of this study was to test whether aspects of the initial non-verbal behaviour of patients with schizophrenia and depression in medical consultations differ and are associated with symptom levels in each group. Sampling and Method: The first 2 min of videotaped outpatient consultations with 78 patients (39 each with schizophrenia and depression) were analysed by researchers who were masked to the diagnosis and symptom levels of the patients. Non-verbal behaviour was assessed using a modified Ethological Coding System for Interviews. Symptom levels were rated by independent researchers on the Positive and Negative Syndrome Scale and Beck Depression Inventory. Results: The 2 diagnostic groups showed significant differences on 1 out of 6 aspects of non-verbal communication, with patients with schizophrenia exhibiting more ‘flight’ behaviour, i.e. more looking down or away, crouching and freezing. Within the group of patients with schizophrenia, more ‘flight’ and less ‘assertion’ were associated with higher symptom levels. Conclusion: Initial ‘flight’ behaviour of patients in medical consultations may be specific for schizophrenia and associated with the symptoms of that illness. Such behaviour might indicate an avoidance of potentially adverse communication, and future research should investigate whether it can also be identified in everyday social interactions other than medical consultations.
A Phase II Trial of Epirubicin, Oxaliplatin, and Capecitabine (EOX) as First-Line Chemotherapy in Advanced Gastric Cancer: A Chinese Single-Center Experience
Authors: Xiang Xiao Jun , Qiu Feng , Xiong Jian Ping , Zhang Ling , Yu Feng , Feng Miao , Zhan Zheng Yu
Published: April 2010

Objective: This study aimed at evaluating the efficacy and safety of epirubicin, oxaliplatin, and capecitabine (EOX) in advanced gastric cancer (AGC) patients in the Chinese population. Patients and Methods: Patients with previously untreated advanced measurable gastric cancer received epirubicin (50 mg/m2, day 1), oxaliplatin (130 mg/m2 2-hour infusion, day 1) and capecitabine (625 mg/m2 orally, twice daily, days 1–21) every 3 weeks.Results: Of 48 enrolled patients, 47 were evaluable for efficacy and 48 for toxicity. A median of five cycles (range 1–8) was administered. The overall response rate was 51.1% (95% CI 36–66) with two complete responses, 22 partial responses, 16 stable diseases, and 7 progressions. Median progression-free survival was 6.5 months (95% CI 5.6–7.4) and median overall survival was 10.4 months (95% CI 8.8–12.0). Grade 3–4 neutropenia and anemia were observed in 22.9 and 6.3% of patients, respectively. Grade 3–4 nonhematological toxicities included alopecia (18.9%), nausea (8.3%), vomiting (6.3%), diarrhea (6.3%), hand-foot syndrome (4.2%) and neurological toxicity (2.1%). Conclusion: In our experience, the EOX regimen was highly effective, well tolerated and conveniently delivered as first-line chemotherapy for AGC patients in the Chinese population.
Disability and Depressive Symptoms in Later Life: The Stress-Buffering Role of Informal and Formal Support
Authors: Chan Natalie , Anstey Kaarin J. , Windsor Tim D. , Luszcz Mary A.
Published: April 2010

Background: Despite the increasing utilization of formal services by older adults in many nations, there is a paucity of research that has examined the relationships between disability, formal support and depressive symptoms in later life. Objective: We investigated whether support received for daily activities, either from formal and/or informal sources, weakened the deleterious relationship between disability and depression symptoms in later life and whether these stress-buffering effects were stronger in later years of older adulthood. Methods: Participants were 1,359 community-dwelling older adults drawn from Wave 1 of the Australian Longitudinal Study of Ageing. Hierarchical multiple regression was used. Results: Individuals receiving support from (1) informal sources only and (2) both informal and formal sources had weaker relationships between disability and depressive symptoms, relative to those receiving no support. The interaction between informal and formal support and disability also revealed that for individuals with above average functional limitations, receipt of this support type was associated with fewer depressive symptoms. However, for individuals with no functional limitations, receipt of both informal and formal support was not associated with depressive symptoms. The stress-buffer age variation hypothesis received no support. Conclusions: Findings suggest that receiving a combination of informal and formal support may be sufficient to offset the harmful association between disability and depressive symptoms in later life. In addition, findings further emphasized the importance of informal support in later life. In contrast, formal support in isolation may not be sufficient to confer a protective effect. Given the expected increase in utilization of formal services among older adults in the coming decades, it is essential that future research investigates the possible factors that underlie this null result.
Privileges and Immunities of Global Public-Private Partnerships: A Case study of the Global Fund to Fight AIDs, Tuberculosis and Malaria
Authors: Aziz Davinia Abdul
Published: April 2010

The question of whether it is at all appropriate to extend privileges and immunities regimes beyond international organizations to the increasingly ubiquitous global public-private partnership structure has received little attention to date in the scholarly literature. This article examines this question through a study of the Global Fund to Fight AIDS, Tuberculosis and Malaria, a permanent global public-private partnership that formally incorporates non-state actors as equal players in its core governance structures. The article concludes that considerations of genesis and administrative law-type analyses of institutional design may, to some extent, substitute for the constituent treaty of classical international law in order to identify which global public-private partnerships should benefit from privileges and immunities, as well as the specific privileges and immunities to be granted in each case to facilitate the effective fulfilment of these partnerships' mandates.
Democracy Promotion, Civil Society Building, and the Primacy of Politics
Authors: Jamal Manal A.
Published: April 2010

Since 1991, Western bilateral and multilateral democracy promotion assistance, especially for civil society development, has increased dramatically. Much of the literature that assesses the impact of this assistance has focused on either direct recipients in civil society or macro transformations, with minimal systematic analysis of how developments in civil society unfold. This article argues that political settlements shape the impact of Western civil society building initiatives. The inclusivity of political settlements can determine who receives funding and who does not and also influences the representativeness of political institutions. In contexts with noninclusive political settlements, where certain groups are excluded from the settlement and the settlement enjoys minimal support, democracy promotion efforts are more likely to exacerbate polarization, thereby weakening the quality of civil society. Examining the women’s sector of civil society in the Palestinian territories and El Salvador, this article illustrates the primacy of political settlements and the limitations of civil society building in contexts where certain actors are excluded from the onset.
Development of a new control device for stabilizing blood level in reservoir during extracorporeal circulation
Authors: Momose Naoki , Yamakoshi Rie , Kokubo Ryo , Yasuda Toru , Iwamoto Norio , Umeda Chinori , Nakajima Itsuro , Yanagisawa Mitsunobu , Tomizawa Yasuko
Published: April 2010

We developed a simple device that stabilizes the blood level in the reservoir of the extracorporeal circulation open circuit system by measuring the hydrostatic pressure of the reservoir to control the flow rate of the arterial pump. When the flow rate of the venous return decreases, the rotation speed of the arterial pump is automatically slowed down. Consequently, the blood level in the reservoir is stabilized quickly between two arbitrarily set levels and never falls below the pre-set low level. We conducted a basic experiment to verify the operation of the device, using a mock circuit with water. Commercially available pumps and reservoir were used without modification. The results confirmed that the control method effectively regulates the reservoir liquid level and is highly reliable. The device possibly also functions as a safety device.
An Examination of Direct and Indirect Effects of Maltreatment Dimensions and Other Ecological Risks on Persistent Youth Offending
Authors: Verrecchia P.J. , Fetzer Matthew D. , Lemmon John H. , Austin Thomas L.
Published: April 2010

The study examined the ecological model by testing the direct and indirect effects of four maltreatment dimensions (supervisory neglect, age at onset, recurrence, and severity) on persistent youth offending. A path model was constructed hypothesizing that maltreatment, family functioning, and community risks would increase behavior and academic problems in childhood and delinquency in adolescence. The design featured within-group analysis that included methodological and statistical controls determining how variations in maltreatment affect delinquent behavior among maltreated children. Supervisory neglect produced direct and indirect effects. Maltreatment severity produced direct effects only. Family functioning and community risks produced indirect effects. The results support the ecological explanation of the maltreatment/delinquency link. The key implication of the study is that accurate and early identification of maltreatment, coupled with interventions that improve parental discipline and supervision, will reduce persistent youth offending while also mediating the effects of other risk factors.
TV Comedy Audiences and Media Technology
Authors: Kalviknes Bore Inger-Lise
Published: April 2010

Drawing on focus group data, this article explores the ways in which British and Norwegian viewers constructed the role of media technology in their engagement with TV comedy. Arguing that TV comedy on pre-recorded DVDs tended to have far greater significance for British participants than Norwegian participants, the article maintains that this technology had different sets of cultural meanings in the two national contexts. The discussion examines factors that might contribute to this national difference, and considers how DVD usage may affect audience engagement. While DVDs have been seen to address viewers as fan consumers or collectors, most of these users primarily associated this technology with the convenience of timeshifting. Along with VHS and video files, DVDs were seen to offer viewers greater control over when and how they wanted to engage with TV comedy.
Effective Communications Regulation in an Era of Convergence?
Authors: Simpson Seamus
Published: April 2010

This article explores recent problems with premium rate number service (PRS) use in UK participation TV, utilizing a regulatory convergence analytical framework. In 2003, the UK government created the communications convergence regulator, Ofcom, yet PRS regulation continued to remain the responsibility of PhonepayPlus (PPP), originally established in 1986. The article argues that Ofcom could have anticipated the problem concerning TV phone-ins, or at least reacted to adverse developments more quickly. PPP was unable to achieve this because of its regulatory culture and narrower focus. The consequences of the PRS saga have been significant. Damage to the reputation of the PRS business and commercial broadcasters has occurred. Citizen trust in public service broadcasting has been eroded. Regulatory remedies provided by Ofcom and PPP are likely to minimize future system abuses. However, that all PRS-in-TV regulatory activity has not been completely subsumed into Ofcom’s operational structure remains an operational anomaly.
The market, competition, and equality
Authors: Dietsch Peter
Published: April 2010

How much inequality does market interaction generate? The answer to this question partly depends on the level of competition among economic agents. Yet, in their normative analysis of the market, theories of distributive justice focus on individual characteristics such as talents as determinants of income, and tend to ignore structural features such as competition. Economists, on the other hand, dispose of the conceptual tools to assess the distributive impact of competition, but their analysis is usually limited to allocative efficiency. Part I of the article distinguishes my argument from conventional perspectives on income inequality and redistribution. Whereas the latter propose either to redistribute income once the market interaction has taken place or to adjust the initial holdings of market participants, I focus on the distributive impact of the institutional structure of the market itself. Part II outlines the ways in which various forms of competition affect distribution. My objective here is descriptive in nature, but shows that a normative evaluation of the market has to take seriously the distributive impact of competition. This impact can be broken down into the analysis of three overlapping groups of economic agents, namely consumers, workers, and capital owners. Consumers potentially gain from competition in the form of lower prices, but these gains are only realized if competition does not put pressure on their work income at the same time. Unless competition squeezes profits unusually hard, capital owners tend to benefit from competition.
Groups, Teams, and Communities of Practice: A Comparison
Authors: Gilley Ann , Kerno Steven J.
Published: April 2010

Groups, teams, and communities of practice (CoPs) are becoming ubiquitous on the modern landscape. However, the organizational conditions under which these structures are most appropriate and when they are of little or no use have received little attention. This article compares and contrasts groups, teams, and CoPs, and offers guidelines and a word of caution for HRD professionals and their organizations attempting to orchestrate the transition to CoPs.
Kaizen Teams: Integrated HRD Practices for Successful Team Building
Authors: Stone Kyle B.
Published: April 2010

Lean thinking has evolved as an operational strategy over the past few decades and is integral to the fabric of many leading organizations. Within lean organizations, the pursuit of identifying and eliminating non—value-added activities and processes from the value stream is achieved through self-directed teams commonly called kaizen teams. This conceptual article introduces lean thinking, including a brief overview of lean origins, guiding principles for kaizen events and associated teams, and their location within team-building research and literature. Four just-in-time team-building learning modules for kaizen events are presented with appropriate resources for additional research of relevant theories.
Communities of Practice: Beyond Teams
Authors: Kerno Steven J. , Mace Stephanie L.
Published: April 2010

Communities of practice are being incorporated by organizations into internal knowledge management schema, as well as the extended knowledge system, capable of spanning elements from the external environment. This article seeks to explore the positive outcomes associated with the approach as well as potential challenges confronting communities of practice so organizations may more competently manage conditions crucial to their success. An overview of communities of practice, including an historical background, theoretical definition, common characteristics, structural components, benefits, challenges, limitations, and recommendations for organizational success will be presented. A discussion and conclusions section ends this article.
The Clinical Utility of Cardiopulmonary Exercise Testing in Suspected or Confirmed Myocardial Ischemia
Authors: Pinkstaff Sherry , Peberdy Mary Ann , Fabiato Alexander , Finucane Sheryl , Arena Ross
Published: April 2010

Heart disease is a major cause of morbidity and mortality in the United States, with coronary artery disease (CAD) representing more than half of all cardiovascular events. Stable patients presenting with symptoms suggestive of CAD are likely to undergo an exercise electrocardiogram (ECG) and/ or imaging study as a first-line diagnostic assessment. A cardiopulmonary exercise test (CPX) is an ECG stress test plus ventilatory gas analysis. Recently, CPX has been used to detect exercise-induced myocardial ischemia (EIMI) suggestive of underlying CAD. Two CPX variables, oxygen pulse (VO2/HR) and the slope of oxygen consumption versus work rate (Δ VO2/ Δ WR), have been identified to be especially indicative of EIMI. Currently, there are a number of diagnostic tests available for the identification of CAD, with the most widely used being stress ECG, stress myocardial perfusion imaging (MPI) and echocardiography, and cardiac catheterization. Exercise ECG, although inexpensive, has a number of well-recognized limitations, including low sensitivity resulting in false-negative results. Stress (exercise or pharmaceutically induced) MPI and catheterization are more accurate but also more invasive and expensive. It appears that CPX may improve the diagnostic accuracy of exercise ECG. This review will address the potential utility of CPX in patients with suspected or confirmed myocardial ischemia.