bluuebunny/crossref_metadata_2025 huggingface dataset:
Granulocyte Colony-Stimulating Factor (G-CSF) Treatment of Childhood Acute Myeloid Leukemias That Overexpress the Differentiation-DefectiveG-CSFReceptor Isoform IV Is Associated With a Higher Incidence of Relapse
Authors: Ehlers Stephanie , Herbst Christin , Zimmermann Martin , Scharn Nicole , Germeshausen Manuela , von Neuhoff Nils , Zwaan Christian Michel , Reinhardt Katarina , Hollink Iris H. , Klusmann Jan-Henning , Lehrnbecher Thomas , Roettgers Silja , Stary Jan , Dworzak Michael , Welte Karl , Creutzig Ursula , Reinhardt Dirk
Published: April 2010

Purpose

This prospective, multicenter Acute Myeloid Leukemia Berlin-Frankfurt-Muenster (AML-BFM) 98 study randomly tested the ability of granulocyte colony-stimulating factor (G-CSF) to reduce infectious complications and to improve outcomes in children and adolescents with acute myeloid leukemia (AML). However, a trend toward an increased incidence of relapses in the standard-risk (SR) group after G-CSF treatment was observed.

Patients and Methods

Of 154 SR patients in the AML-BFM 98 cohort, 50 patients were tested for G-CSF receptor (G-CSFR) RNA isoform I and IV expression, G-CSFR cell surface expression, and acquired mutations in the G-CSFR gene.

Results

In patients randomly assigned to receive G-CSF after induction, 16 patients overexpressing the G-CSFR isoform IV showed an increased 5-year cumulative incidence of relapse (50% ± 13%) compared with 14 patients with low-level isoform IV expression (14% ± 10%; log-rank P = .04). The level of G-CSFR isoform IV had no significant effect in patients not receiving G-CSF (P = .19). Multivariate analyses of the G-CSF–treated subgroup, including the parameters G-CSFR isoform IV overexpression, sex, and favorable cytogenetics as covariables, revealed the prognostic relevance of G-CSFR isoform IV overexpression for 5-year event-free survival (P = .031) and the 5-year cumulative incidence of relapse (P = .049).

Conclusion

Our results demonstrate that children and adolescents with AMLs that overexpress the differentiation-defective G-CSFR isoform IV respond to G-CSF administration after induction, but with a significantly higher incidence of relapse.
Urologist Density and County-Level Urologic Cancer Mortality
Authors: Odisho Anobel Y. , Cooperberg Matthew R. , Fradet Vincent , Ahmad Ardalan E. , Carroll Peter R.
Published: April 2010

Purpose

The surgical work force distribution at the county level varies widely across the United States, and the impact of differential access on cancer outcomes is unclear. We used urologists as a test case because they are the first care providers for urologic cancers, can easily be identified from available data sources, and are unevenly distributed throughout the country. The goal of this study was to determine the effect of increasing urologist density on local prostate, bladder, and kidney cancer mortality.

Patients and Methods

Using county-level data from the Area Resource File, US Census, National Cancer Institute, and Centers for Disease Control, regression models were built for prostate, bladder, and kidney cancer mortality, controlling for categorized urologist density, county demographics, socioeconomic factors, and preexisting health care infrastructure.

Results

For each of the three cancers, there was a statistically significant cancer-specific mortality reduction associated with counties that had more than zero urologists (16% to 22% reduction for prostate cancer, 17% to 20% reduction for bladder cancer, and 8% to 14% reduction for kidney cancer with increasing urologist density) relative to zero urologists. However, increasing density greater than two urologists per 100,000 people had no statistically significant impact on mortality for any of the tumors studied.

Conclusion

The presence of a urologist is associated with lower mortality for urologic cancers in that county, but increasing urologist density does not yield further improvements. Therefore, a nuanced and geographically aware policy toward the size and distribution of the future work force is most likely to provide the greatest population-level improvement in cancer mortality outcomes.
Acupuncture for Pain and Dysfunction After Neck Dissection: Results of a Randomized Controlled Trial
Authors: Pfister David G. , Cassileth Barrie R. , Deng Gary E. , Yeung K. Simon , Lee Jennifer S. , Garrity Donald , Cronin Angel , Lee Nancy , Kraus Dennis , Shaha Ashok R. , Shah Jatin , Vickers Andrew J.
Published: April 2010

Purpose

To determine whether acupuncture reduces pain and dysfunction in patients with cancer with a history of neck dissection. The secondary objective is to determine whether acupuncture relieves dry mouth in this population.

Patients and Methods

Patients at a tertiary cancer center with chronic pain or dysfunction attributed to neck dissection were randomly assigned to weekly acupuncture versus usual care (eg, physical therapy, analgesia, and/or anti-inflammatory drugs, per patient preference or physician recommendation) for 4 weeks. The Constant-Murley score, a composite measure of pain, function, and activities of daily living, was the primary outcome measure. Xerostomia, a secondary end point, was assessed using the Xerostomia Inventory.

Results

Fifty-eight evaluable patients were accrued and randomly assigned from 2004 to 2007 (28 and 30 patients on acupuncture and control arms, respectively). Constant-Murley scores improved more in the acupuncture group (adjusted difference between groups = 11.2; 95% CI, 3.0 to 19.3; P = .008). Acupuncture produced greater improvement in reported xerostomia (adjusted difference in Xerostomia Inventory = –5.8; 95% CI, –0.9 to –10.7; P = .02).

Conclusion

Significant reductions in pain, dysfunction, and xerostomia were observed in patients receiving acupuncture versus usual care. Although further study is needed, these data support the potential role of acupuncture in addressing post–neck dissection pain and dysfunction, as well as xerostomia.
Oxaliplatin-Mediated Increase in Spleen Size As a Biomarker for the Development of Hepatic Sinusoidal Injury
Authors: Overman Michael J. , Maru Dipen M. , Charnsangavej Chusilp , Loyer Evelyn M. , Wang Huamin , Pathak Priyanka , Eng Cathy , Hoff Paulo M. , Vauthey Jean-Nicolas , Wolff Robert A. , Kopetz Scott
Published: April 2010

Purpose

Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury, with resultant sinusoidal damage and portal hypertension. We sought to explore the relationship between oxaliplatin induced hepatic sinusoidal injury, increases in spleen size, and the subsequent development of thrombocytopenia.

Patients and Methods

We retrospectively assessed the relationship between chemotherapy exposure, changes in spleen size (determined by volumetric measurements), and platelet counts in 136 patients treated with adjuvant fluorouracil and oxaliplatin (FOLFOX) or fluoropyrimidine for stage II or III colorectal adenocarcinoma. Hepatic sinusoidal injury and changes in spleen size were graded in a separate population of 63 patients with metastatic colorectal cancer receiving fluoropyrimidine and oxaliplatin before liver resection.

Results

Spleen size increased in 86% of patients treated with adjuvant FOLFOX (P < .001), with a ≥ 50% increase in 24% of patients. Spleen size did not significantly increase in patients treated with adjuvant fluoropyrimidine. Increases in spleen size correlated with cumulative oxaliplatin dose (P = .003). Patients with splenic enlargement ≥ 50% had higher rates of thrombocytopenia in the first year after completion of chemotherapy (27% v 5%; P = .003). In patients with hepatic metastases treated with preoperative fluoropyrimidine and oxaliplatin, increases in spleen size was a predictor of higher histologic grades of sinusoidal injury in both univariate (P = .03) and multivariate (P = .02) analyses.

Conclusion

Increases in spleen size correlate with increasing grade of hepatic sinusoidal injury and can serve as a simple method for identifying patients at risk for this toxicity. Oxaliplatin-induced increases in spleen size should be recognized as a potential etiology of persistent thrombocytopenia after oxaliplatin treatment.
Anemia in Hodgkin's Lymphoma: The Role of Interleukin-6 and Hepcidin
Authors: Hohaus Stefan , Massini Giuseppina , Giachelia Manuela , Vannata Barbara , Bozzoli Valentina , Cuccaro Annarosa , D'Alo' Francesco , Larocca Luigi Maria , Raymakers Reinier A.P. , Swinkels Dorine W. , Voso Maria Teresa , Leone Giuseppe
Published: April 2010

Purpose

Cytokines play a pivotal role in Hodgkin's lymphoma (HL). Because interleukin-6 (IL-6) induces expression of hepcidin, one of the principal regulators of iron metabolism, we studied the contribution of hepcidin in anemia in HL at diagnosis.

Patients and Methods

Plasma samples from 65 patients with HL were analyzed for hepcidin levels using a combination of weak cation exchange chromatography and time-of-flight mass spectrometry; cytokine levels were analyzed using enzyme-linked immunosorbent assays and parameters of iron metabolism and acute-phase reaction.

Results

Hepcidin plasma levels were significantly higher in HL patients when compared with controls, independent of the presence of anemia (P = .001). In the subset of patients with anemia, hepcidin levels inversely correlated with hemoglobin levels (P = .01). Analyzing parameters of iron metabolism, hepcidin levels showed a positive correlation with ferritin (P < .001) and an inverse correlation to iron and iron-binding capacity. Hepcidin strongly correlated to IL-6 levels (P < .001) but not to IL-10 or thymus and activation-regulated cytokine (TARC)/chemokine (C-C motif) ligand 17 (CCL17) levels. In a multivariate regression analysis, IL-6 and fibrinogen levels were independently associated with hepcidin. Higher hepcidin levels were observed in patients with more aggressive disease characteristics: stage IV disease (P = .01), presence of B symptoms (P = .03), and International Prognostic Score > 2 (P = .005).

Conclusion

Our findings suggest that in HL, hepcidin is upregulated by IL-6. Elevated hepcidin levels result in iron restriction and signs of anemia of chronic inflammation, although hepcidin-independent mechanisms contribute to development of anemia in HL.
Spironolactone Improves Glucose and Lipid Metabolism by Ameliorating Hepatic Steatosis and Inflammation and Suppressing Enhanced Gluconeogenesis Induced by High-Fat and High-Fructose Diet
Authors: Wada Tsutomu , Kenmochi Hiroki , Miyashita Yusuke , Sasaki Motohiro , Ojima Minoru , Sasahara Masakiyo , Koya Daisuke , Tsuneki Hiroshi , Sasaoka Toshiyasu
Published: April 2010

Recent evidence suggests that treatment with mineralocorticoid receptor antagonist suppressed local inflammation in vascular tissues or cardiomyocytes; therefore, we examined the effect of spironolactone on glucose and lipid metabolism in a mouse model with diet-induced diabetes and nonalcoholic fatty liver disease. C57BL/6 mice were fed either the control diet, 60% fat diet with 30% fructose water (HFFD), or HFFD with spironolactone for 8 wk. HFFD mice demonstrated apparent phenotypes of metabolic syndrome, including insulin resistance, hypertension, dyslipidemia, and fatty liver. Although treatment with spironolactone did not affect the increased calorie intake and body weight by HFFD, the increments of epididymal fat weight, blood pressure, serum triglyceride, free fatty acids, leptin, and total cholesterol levels were significantly suppressed. Elevation of blood glucose during glucose and insulin tolerance tests in HFFD mice was significantly lowered by spironolactone. Notably, increased glucose levels during pyruvate tolerance test in HFFD mice were almost completely ameliorated to control levels by the treatment. Staining with hematoxylin-eosin (HE) and Oil-red-O demonstrated marked accumulation of triglycerides in the centrilobular part of the hepatic lobule in HFFD mice, and these accumulations were effectively improved by spironolactone. Concomitantly HFFD feeding markedly up-regulated hepatic mRNA expression of proinflammatory cytokines (TNFα, IL-6, and monocyte chemoattractant protein-1), gluconeogenic gene phosphoenolpyruvate carboxykinase, transcription factor carbohydrate response element binding protein, and its downstream lipogenic enzymes, all of which were significantly suppressed by spironolactone. These results indicate that inhibition of mineralocorticoid receptor might be a beneficial therapeutic approach for diet-induced phenotypes of metabolic syndrome and fatty liver.
Electrical and Morphological Characteristics of Anteroventral Periventricular Nucleus Kisspeptin and Other Neurons in the Female Mouse
Authors: Ducret Eric , Gaidamaka Galina , Herbison Allan E.
Published: April 2010

Neurons in the rodent anteroventral periventricular nucleus (AVPV) play a key role in integrating circadian and gonadal steroid hormone information in the control of fertility. In particular, estradiol-sensitive kisspeptin neurons located in the AVPV, and adjacent structures [together termed the rostral periventricular area of the third ventricle (RP3V)], are critical for puberty onset and the preovulatory LH surge. The present study aimed to establish the morphological and electrical firing characteristics of RP3V neurons, including kisspeptin neurons, in the adult female mouse. Cell-attached electrical recordings, followed by juxtacellular dye filling, of 129 RP3V neurons in the acute brain slice preparation revealed these cells to exhibit multipolar (53%), bipolar (43%), or unipolar (4%) dendritic morphologies along with silent (16%), irregular (41%), bursting (25%), or tonic (34%) firing patterns. Postrecording immunocytochemistry identified 17 of 100 filled RP3V cells as being kisspeptin neurons, all of which exhibited complex multipolar dendritic trees and significantly (P < 0.05) higher bursting or high tonic firing rates compared with nonkisspeptin neurons. The firing pattern of RP3V neurons fluctuated across the estrous cycle with a significant (P < 0.05) switch from irregular to tonic firing patterns found on proestrus. A similar nonsignificant trend was found for kisspeptin neurons. All RP3V neurons responded to γ-aminobutyric acid and glutamate, about 10% to RFamide-related peptide-3, about 5% to vasopressin, 0% to vasoactive intestinal peptide, and 0% to kisspeptin. These studies provide a morphological and electrical description of AVPV/RP3V neurons and demonstrate their cycle-dependent firing patterns along with an unexpected lack of acute response to the circadian neuropeptides.
BMP-9 induces proliferation of multiple types of endothelial cells in vitro and in vivo
Authors: Suzuki Yuka , Ohga Noritaka , Morishita Yasuyuki , Hida Kyoko , Miyazono Kohei , Watabe Tetsuro
Published: April 2010

Members of the bone morphogenetic protein (BMP) family have been implicated in the development and maintenance of vascular systems. Whereas members of the BMP-2/4 and osteogenic protein-1 groups signal via activin receptor-like kinase (ALK)-2, ALK-3 and ALK-6, BMP-9 and BMP-10 have been reported to bind to ALK-1 in endothelial cells. However, the roles of BMP-9–ALK-1 signaling in the regulation of endothelial cells have not yet been fully elucidated. Here, using various systems, we examined the effects of BMP-9 on the proliferation of endothelial cells. Vascular-tube formation from ex vivo allantoic explants of mouse embryos was promoted by BMP-9. BMP-9, as well as BMP-4 and BMP-6, also induced the proliferation of in-vitro-cultured mouse embryonic-stem-cell-derived endothelial cells (MESECs) by inducing the expression of vascular endothelial growth factor receptor 2 and Tie2, a receptor for angiopoietin-1. A decrease in ALK-1 expression or expression of constitutively active ALK-1 in MESECs abrogated and mimicked the effects of BMP-9 on the proliferation of MESECs, respectively, suggesting that BMP-9 promotes the proliferation of these cells via ALK-1. Furthermore, in vivo angiogenesis was promoted by BMP-9 in a Matrigel plug assay and in a BxPC3 xenograft model of human pancreatic cancer. Consistent with these in vivo findings, BMP-9 enhanced the proliferation of in-vitro-cultured normal endothelial cells from dermal tissues of adult mice and of tumor-associated endothelial cells isolated from tumor xenografts in host mice. These findings suggest that BMP-9 signaling activates the endothelium tested in the present study via ALK-1.
MUC1 regulates nuclear localization and function of the epidermal growth factor receptor
Authors: Bitler Benjamin G. , Goverdhan Aarthi , Schroeder Joyce A.
Published: April 2010

Alteration of protein trafficking and localization is associated with several diseases, including cystic fibrosis, breast cancer, colorectal cancer, leukemia and diabetes. Specifically, aberrant nuclear localization of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, is a poor prognostic indicator in several epithelial carcinomas. It is now appreciated that in addition to signaling from the plasma membrane, EGFR also trafficks to the nucleus, and can directly bind the promoter regions of genes encoding cyclin D1 (CCND1) and B-Myb (MYBL2). We have previously established that loss of MUC1 in an EGFR-dependent transgenic mouse model of breast cancer correlates with the loss of cyclin D1 expression. Here, we provide evidence for a novel regulatory function of MUC1 in the trafficking and nuclear activity of EGFR. We found that MUC1 and EGFR interact in the nucleus of breast cancer cells, which promotes the accumulation of chromatin-bound EGFR. Additionally, the presence of MUC1 results in significant colocalization of EGFR and phosphorylated RNA polymerase II, indicating that MUC1 influences the association of EGFR with transcriptionally active promoter regions. Importantly, we found that the loss of MUC1 expression resulted in a decrease in the interaction between EGFR and the CCND1 promoter, which translated to a significant decrease in cyclin D1 protein expression. This data offers insights into a novel regulatory mechanism of EGFR nuclear function and could have important implications for evaluating nuclear localization in cancer.
The Arabidopsis DJ-1a protein confers stress protection through cytosolic SOD activation
Authors: Xu Xiang Ming , Lin Hong , Maple Jodi , Björkblom Benny , Alves Guido , Larsen Jan Petter , Møller Simon Geir
Published: April 2010

Mutations in the DJ-1 gene (also known as PARK7) cause inherited Parkinson's disease, which is characterized by neuronal death. Although DJ-1 is thought to be an antioxidant protein, the underlying mechanism by which loss of DJ-1 function contributes to cell death is unclear. Human DJ-1 and its Arabidopsis thaliana homologue, AtDJ-1a, are evolutionarily conserved proteins, indicating a universal function. To gain further knowledge of the molecular features associated with DJ-1 dysfunction, we have characterized AtDJ-1a. We show that AtDJ-1a levels are responsive to stress treatment and that AtDJ-1a loss of function results in accelerated cell death in aging plants. By contrast, transgenic plants with elevated AtDJ-1a levels have increased protection against environmental stress conditions, such as strong light, H2O2, methyl viologen and copper sulfate. We further identify superoxide dismutase 1 (SOD1) and glutathione peroxidase 2 (GPX2) as interaction partners of both AtDJ-1a and human DJ-1, and show that this interaction results in AtDJ-1a- and DJ-1-mediated cytosolic SOD1 activation in a copper-dependent fashion. Our data have highlighted a conserved molecular mechanism for DJ-1 and revealed a new protein player in the oxidative stress response of plants.
Angiotensin-II-induced apoptosis requires regulation of nucleolin and Bcl-xL by SHP-2 in primary lung endothelial cells
Authors: Lee Young H. , Mungunsukh Ognoon , Tutino Rebecca L. , Marquez Ana P. , Day Regina M.
Published: April 2010

Angiotensin II (Ang II) is a key proapoptotic factor in fibrotic tissue diseases. However, the mechanism of Ang-II-induced cell death in endothelial cells has not been previously elucidated. Using the neutral comet assay and specific receptor antagonists and agonists, we found that Ang-II-mediated apoptosis in primary pulmonary endothelial cells required the AT2 receptor. Ang II caused cytochrome c release from the mitochondria concurrent with caspase-3 activation and DNA fragmentation, and apoptosis was suppressed by an inhibitor of Bax-protein channel formation, implicating mitochondrial-mediated apoptosis. There was no evidence that the extrinsic apoptotic pathway was involved, because caspase-9, but not caspase-8, was activated by Ang-II treatment. Apoptosis required phosphoprotein phosphatase activation, and inhibition of the SHP-2 phosphatase (encoded by Ptpn11) blocked cell death. Reduced levels of anti-apoptotic Bcl-2-family members can initiate intrinsic apoptosis, and we found that Ang-II treatment lowered cytosolic Bcl-xL protein levels. Because the protein nucleolin has been demonstrated to bind Bcl-xL mRNA and prevent its degradation, we investigated the role of nucleolin in Ang-II-induced loss of Bcl-xL. RNA-immunoprecipitation experiments revealed that Ang II reduced the binding of nucleolin to Bcl-xL mRNA in an AU-rich region implicated in instability of Bcl-xL mRNA. Inhibition of SHP-2 prevented Ang-II-induced degradation of Bcl-xL mRNA. Taken together, our findings suggest that nucleolin is a primary target of Ang-II signaling, and that Ang-II-activated SHP-2 inhibits nucleolin binding to Bcl-xL mRNA, thus affecting the equilibrium between pro- and anti-apoptotic members of the Bcl-2 family.
Generalised Concept of Molar Absorption Coefficient for Non-Uniform Water Absorbance Patterns
Authors: Ikehata Akifumi
Published: April 2010

Aquaphotomics elucidates the use of the water–light interaction at all frequencies of the electromagnetic spectrum as a molecular mirror. The aquaphotome is the entire complement of water molecules' absorbance bands in aqueous and biological systems, i.e. a comprehensive spectral assignment of all existing water absorbance bands. development of the aquaphotome means constructing a data base of characteristic water absorbance bands and patterns in order to identify respective molecules surrounded by water. as it requires a huge amount of work and contributions from various scientific fields, development of new experimental designs and methods of spectral data analysis, the aquaphotomics column has started inviting contributions from scientists active in various fields. our first guest is Dr Ikehata from the National food research Institute in Japan. for a generalised analysis of absorption spectra of non-ideal mixtures, such as aqueous systems, he and his colleagues have recently proposed the use of partial molar absorption (PMA) and excess partial molar absorption (EPMA) with no wavelength limit. Calculating the generalised absorptivity is going to assist water band assignment and the interpretation of regression coefficients and loading plots in each study.— Roumiana Tsenkova
Validity of estimating non-sex hormone-binding globulin bound testosterone and oestradiol from total hormone measurements in boys and girls
Authors: Egleston Brian L , Chandler D Walt , Dorgan Joanne F
Published: April 2010

Background

Circulating levels of bioavailable oestradiol and testosterone are often desirable for clinical practice or investigational studies of children. However, assays to measure circulating hormone levels might not always be accessible. We sought to validate the empirical calculation of circulating bioavailable testosterone and oestradiol in children.

Methods

Six hundred and sixty-three eight- to 10-year olds were recruited to the Dietary Intervention Study in Children (DISC). DISC was a randomized clinical trial designed to test efficacy of a dietary intervention to reduce serum cholesterol (LDL-C) in children with elevated cholesterol. Assay measures of oestradiol, testosterone, sex hormone-binding globulin concentration (SHBG) and albumin concentration in girls as well as dihydrotestosterone in boys were measured for up to 10 y. We calculated measures of circulating non-SHBG bound oestradiol and testosterone from total hormone levels using the law of mass action. We compared proportional differences in assay measured minus calculated non-SHBG bound hormone levels versus their averages using generalized estimating equations-estimated linear regressions.

Results

On average, calculated values overestimated assay measured values (−11.7% for non-SHBG bound oestradiol in girls and −2.6% for non-SHBG bound testosterone in boys). The intercept and slope of the regression for non-SHBG bound oestradiol in girls were −0.13 (95% confidence interval [CI] −0.14 to −0.12) and 0.005 (95% CI 0.003–0.007), respectively. The intercept and slope for non-SHBG bound testosterone in boys were −0.16 (95% CI −0.17 to −0.14) and 0.0006 (95% CI 0.0005–0.0006).

Conclusion

While calculated values might be useful for research purposes, they are generally not close enough for clinical purposes.
Hunting down a double gap metabolic acidosis
Authors: Yan Ming-Tso , Chau Tom , Cheng Chih-Jen , Lin Shih-Hua
Published: April 2010

Double gap metabolic acidosis occurs in the setting of unmeasured active osmoles in the serum (osmolal gap) and anion gap (AG) metabolic acidosis. We describe a 67-year-old woman with acute respiratory failure on mechanical ventilator from pneumonia and anuric acute on chronic renal failure (urea nitrogen 21.4 mmol/L, creatinine 530.4 μmol/L) requiring haemodialysis (HD). On hospital day 5, she was found to have progressive metabolic acidosis (serum pH 7.16, PCO2 4.38 kPa, HCO3− 12.1 mmol/L and AG 21 mmol/L). There was no evidence of hypoxaemia, hypoperfusion or haemodynamic instability. Normal serum ketone and l-lactate but high serum osmolal gap (89.4 mmol/kg) was detected. A search for toxic alcohols revealed a high serum propylene glycol (PG 32.9 mmol/L), a stabilizing solvent for intravenous formulations of lorazepam, which was being used as sedation for mechanical ventilation. Unexpectedly, serum l- and d-lactate as metabolites of PG were not elevated. Although extended HD for eight hours completely removed serum PG and the osmolal gap, the predialysis high AG metabolic acidosis persisted, potentially related to hypercatabolism and anuric renal failure. PG should be in the differential diagnosis of the disorders with high osmolar gap and may not always be associated with l- or d-lactic acidosis.
Superficial siderosis – mechanism of disease: an alternative hypothesis
Authors: Nanda Sudip , Sharma Shree Gopal , Longo Santo
Published: April 2010

Superficial siderosis is an increasingly common diagnosis due to advances in imaging. Resulting from the presence of blood in the subarachnoid space, it leads to progressively debilitating ataxia, deafness and myelopathy. Magnetic resonance imaging has revolutionized diagnosis and management of this condition. In one-third of patients with this diagnosis, no subarachnoid bleed can be identified. A lack of sensitivity in our ability to detect subarachnoid bleed is a possible explanation in this group of patients. A novel approach would be to consider defects in the body's defense against intracranial iron overload as a possible cause of this disease. A disproportionately few patients develop superficial siderosis compared with the number who develop subarachnoid bleed from various clinical conditions. Normal physiological protective mechanisms exist in the central nervous system to protect it from damage by blood, haeme or free iron. Deficiency and defect of these protective mechanisms can provide insight into the pathogenetic mechanism of the group of patients where no subarachnoid haemorrhage is identified.
Bivariate Stochastic Dominance and Substitute Risk-(In)dependent Utilities
Authors: Denuit Michel , Eeckhoudt Louis
Published: April 2010

In this paper, we show that, despite their rigid analytical form, substitute risk-independent utilities have a much wider applicability than expected. Our contribution extends that of Mosler (Mosler, K. C. 1984. Stochastic dominance decision rules when the attributes are utility independent. Management Sci. 30(11) 1311–1322) by considering utility functions that exhibit properties beyond nonsatiation and risk aversion (e.g., prudence and temperance). By using the widespread idea of correlation aversion, substitute risk-independent utilities are shown to generate bivariate stochastic dominance. As an application, portfolios are compared to assess the possible hedging effect between two outcomes.
Innovative in-flight glass-melting technology using thermal plasmas
Authors: Watanabe Takayuki , Yatsuda Kazuyuki , Yao Yaochun , Yano Tetsuji , Matuura Tsugio
Published: April 2010

A stable 12-phase AC arc was generated by transformers at a commercial electric power system, and the arc behavior was characterized by image analysis. For the unique advantages, the multiphase AC arc was developed to apply to in-flight glass melting for the purpose of energy-saving and emission reduction. The effects of electrode configuration and sheath gas flow rate on the arc and melting behavior of granulated glass raw material were investigated. Results show that the discharge behavior and the high-temperature region can be controlled by the electrode configuration. The luminance area of the high-temperature region and its fluctuation reflect the discharge behavior. The vitrification degree of glass raw material is mostly dependent on the center temperature of arc. As sheath gas flow rate increases, the ratio of luminance area decreases and the center temperature of arc increases.
Modeling of the plasma chemistry and plasma–surface interactions in reactive plasmas
Authors: Bogaerts Annemie , De Bie Christophe , Eckert Maxie , Georgieva Violeta , Martens Tom , Neyts Erik , Tinck Stefan
Published: April 2010

In this paper, an overview is given of modeling activities going on in our research group, for describing the plasma chemistry and plasma–surface interactions in reactive plasmas. The plasma chemistry is calculated by a fluid approach or by hybrid Monte Carlo (MC)–fluid modeling. An example of both is illustrated in the first part of the paper. The example of fluid modeling is given for a dielectric barrier discharge (DBD) in CH4/O2, to describe the partial oxidation of CH4 into value-added chemicals. The example of hybrid MC–fluid modeling concerns an inductively coupled plasma (ICP) etch reactor in Ar/Cl2/O2, including also the description of the etch process. The second part of the paper deals with the treatment of plasma–surface interactions on the atomic level, with molecular dynamics (MD) simulations or a combination of MD and MC simulations.
Microplasma generation in artificial media and its potential applications
Authors: Tachibana Kunihide
Published: April 2010

Unlike the generation of uniform plasmas in a large volume, structured plasma comprising microplasmas has attracted increasing scientific and technological interest in recent years. Similarly, the concept of plasma generation in artificial media with gas–gas, gas–liquid, and gas–solid interfaces under intentionally organized and controlled conditions has the potential to open a new field in plasma science and technology. Amongst the subtopics of plasma generation in artificial media, we discuss here those dealing with micro-plasma jets in flowing gas channels, microdischarges within microbubbles generated in aqueous electrolyte solutions, and discharges in bubbled water and misted air. Our discussion is supported by preliminary results and aims to stimulate future systematic and quantitative investigations.
Atmospheric-pressure plasma sources: Prospective tools for plasma medicine
Authors: Weltmann Klaus Dieter , Kindel Eckhard , von Woedtke Thomas , Hähnel Marcel , Stieber Manfred , Brandenburg Ronny
Published: April 2010

Plasma-based treatment of chronic wounds or skin diseases as well as tissue engineering or tumor treatment is an extremely promising field. First practical studies are promising, and plasma medicine as an independent medical field is emerging worldwide. While during the last years the basics of sterilizing effects of plasmas were well studied, concepts of tailor-made plasma sources which meet the technical requirements of medical instrumentation are still less developed. Indeed, studies on the verification of selective antiseptic effects of plasmas are required, but the development of advanced plasma sources for biomedical applications and a profound knowledge of their physics, chemistry, and parameters must be contributed by physical research. Considering atmospheric-pressure plasma sources, the determination of discharge development and plasma parameters is a great challenge, due to the high complexity and limited diagnostic approaches. This contribution gives an overview on plasma sources for therapeutic applications in plasma medicine. Selected specific plasma sources that are used for the investigation of various biological effects are presented and discussed. Furthermore, the needs, prospects, and approaches for its characterization from the fundamental plasma physical point of view will be discussed.
Plasma functionalization of textiles: Specifics and possibilities
Authors: Guimond Sebastien , Hanselmann Barbara , Amberg Martin , Hegemann Dirk
Published: April 2010

Plasma technology offers many interesting possibilities for the production of high-value-added textiles. Nevertheless, textiles can have a considerable structural and chemical complexity, and their properties must be taken into account for the implementation of plasma processes. The influences of some of these properties are highlighted through several examples of recent interesting applications, such as the metallization of polyester yarns, the enhancement of fabric moisture wicking and the surface functionalization with plasma polymerization.
Diagnostic-based modeling on a micro-scale atmospheric-pressure plasma jet
Authors: Waskoenig Jochen , Niemi Kari , Knake Nikolas , Graham Lucy Marie , Reuter Stephan , Schulz-von der Gathen Volker , Gans Timo
Published: April 2010

Diagnostic-based modeling (DBM) actively combines complementary advantages of numerical plasma simulations and relatively simple optical emission spectroscopy (OES). DBM is applied to determine spatial absolute atomic oxygen ground-state density profiles in a micro atmospheric-pressure plasma jet operated in He–O2. A 1D fluid model with semi-kinetic treatment of the electrons yields detailed information on the electron dynamics and the corresponding spatio-temporal electron energy distribution function. Benchmarking this time- and space-resolved simulation with phase-resolved OES (PROES) allows subsequent derivation of effective excitation rates as the basis for DBM. The population dynamics of the upper O(3p3P) oxygen state (λ = 844 nm) is governed by direct electron impact excitation, dissociative excitation, radiation losses, and collisional induced quenching. Absolute values for atomic oxygen densities are obtained through tracer comparison with the upper Ar(2p1) state (λ = 750.4 nm). The resulting spatial profile for the absolute atomic oxygen density shows an excellent quantitative agreement to a density profile obtained by two-photon absorption laser-induced fluorescence spectroscopy.
Plasma catalysis: A solution for environmental problems
Authors: Whitehead J. Christopher
Published: April 2010

The combination of a nonthermal, atmospheric plasma with a catalyst is investigated as a means of destroying pollutants in waste gas streams. Using the examples of dichloromethane (DCM) and toluene in air streams, it is shown that the destruction of the pollutant can be increased whilst lowering the operating temperature, giving increasing energy efficiency. Unwanted by-products can also be reduced selectively by appropriate choice of catalyst and of the plasma–catalyst configuration. By studying the temperature dependence of plasma catalysis, some ideas can be obtained about the nature of the interaction between plasma and catalyst in the processing.
Laboratory testing during critical care transport: point-of-care testing in air ambulances
Authors: Di Serio Francesca , Petronelli Maria Antonia , Sammartino Eugenio
Published: April 2010

Air and ground transport are used for prehospital transport of patients in acute life-threatening situations, and increasingly, critically ill patients undergo interhospital transportation. Results from clinical studies suggest that critical tests performed during the transport of critically ill patients presents a potential opportunity to improve patient care. Our project was to identify, according to the recommendations published at this time, a model of point-of-care testing (POCT) (arterial blood gases analysis and glucose, sodium, potassium, ionized calcium, hematocrit/hemoglobin measurements) in air ambulances. In order to identify the key internal and external factors that are important to achieving our objective, an analysis of the Strengths, Weaknesses, Opportunities, and Threats (SWOT analysis) was incorporated into our planning model prior to starting the project. To allow the entire POCT process (pre-, intra-, and post-analytic steps) to be under the control of the reference laboratory, an experimental model of information technology was applied. Real-time results during transport of critically ill patients must be considered to be an integral part of the patient care process and excellent channels of communication are needed between the intensive care units, emergency medical services and laboratories. With technological and computer advances, POCT during critical care transport will certainly increase in the future: this will be a challenge from a laboratory and clinical context.

Clin Chem Lab Med 2010;48:955–61.
PATHFAST™ NT-proBNP (N-terminal-pro B type natriuretic peptide): a multicenter evaluation of a new point-of-care assay
Authors: Zaninotto Martina , Mion Monica Maria , Di Serio Francesca , Caputo Marco , Ottomano Cosimo , Plebani Mario
Published: April 2010

Background: The biochemical determination of cardiac natriuretic peptides, primarily brain natriuretic peptide (BNP) and the amino-terminal fragment of its pro-hormone proBNP (NT-proBNP), are reliable tools for diagnosing cardiac disease, establishing prognosis and evaluating the effectiveness of treatment. These biomarkers have proven to be of particular value in the management of chronic and acute heart failure patients, and in the outpatient and the emergency setting.

Methods: A multicenter evaluation was performed to assess the practicability, and the analytical and clinical performance of a new point-of-care testing (POCT) PATHFAST™ NT-proBNP assay. This is an immunochemiluminescent assay using two polyclonal antibodies in a sandwich test format, and performed with a PATHFAST™ automated analyzer.

Results: The limit of detection (mean+3 SD of the signal of 20 replicates of the zero calibrator obtained in one run) was 0.535 ng/L. An imprecision study, performed in accordance with the CLSI protocol, showed coefficients of variation of 4.0%–6.4% (within-run imprecision), 0.0%–3.4% (between-run imprecision), 5.5%–7.2% (between-day imprecision), 7.6%–8.9% (total imprecision). The method was linear to 28,755 ng/L. Slopes and intercepts ranged from 0.89 to 0.90 and from 10.96 to 22.85, respectively when lithium-heparin plasma samples (n=100) were used to compare the assay under evaluation with the routine laboratory methods (Dimension RxL®, Stratus® CS). When testing matched samples (n=52), a significant difference was found between the 50th percentile NT-proBNP concentration in K2EDTA whole blood, K2EDTA plasma, lithium-heparin plasma and serum. No significant interference was observed for NT-proBNP in lipemic (tryglicerides up to 28.54 mmol/L), icteric (total and conjugated bilirubin up to 513 and 13 μmol/L, respectively) or hemolyzed (hemoglobin up to 13.50 g/L) samples. The NT-proBNP concentration in a group of 180 healthy donors was significantly influenced by age and gender. In a selected population of patients (n=56) with acute dyspnea admitted to the emergency department, a marked reduction in cardiac natriuretic peptide concentrations was observed in hospitalized patients suffering from heart failure who had a better prognosis compared with those with a poorer prognosis (NT-proBNP mean Δ change, % from –22 to –71 vs. +9 to –11).

Conclusions: The satisfactory analytical and clinical performance of the PATHFAST™ NT-proBNP assay, together with its excellent practicability, suggests that it would be a reliable tool in clinical practice, in the emergency setting for point-of-care testing, as well as in the central laboratory.

Clin Chem Lab Med 2010;48:1029–34.
Verdeckte Sacheinlage und (unzulässiges) Hin- und Herzahlen einer Einlage nach dem MoMiG – ein Überblick
Authors: Sporré Oliver
Published: April 2010

Wenn Gesellschafter einer GmbH versuchen, ihrer Verpflichtung zur Leistung der Gesellschaftereinlage durch eine sog. verdeckte Sacheinlage oder ein Hin- und Herzahlen nachzukommen, gehen sie ein erhebliches Risiko ein, die Einlage (nochmals) leisten zu müssen, so z. B. bei einer Insolvenz der Gesellschaft. Der Gesetzgeber hat durch das MoMiG in § 19 Abs. 4 und 5 GmbHG nunmehr die verdeckte Sacheinlage und das Hin- und Herzahlen geregelt und bestimmt, unter welchen Voraussetzungen der Gesellschafter dadurch von der Leistung der Gesellschaftereinlage befreit wird.
Peeling the onion: Outcomes to origins in retrograde narrative
Authors: Ireland Ken
Published: April 2010

Relatively uncommon in fiction as a whole, the procedure of telling-in-reverse offers a range of unexpected and unconventional perspectives. By commencing at a terminal juncture, the fictional trajectory is directed towards past rather than future. Stressing how and why rather than what, retrograde narrative engages readers by supplying results before causes, sustaining curiosity when the later stages of events are known, but exploiting the characters' relative ignorance of what lies ahead of them, and forcing readers to confront their own processes of response and memory, to make sense of material already presented. Illustrations from fiction by Sarah Waters, Martin Amis, John Banville, and Elizabeth Jane Howard are supplemented by examples from drama and film, to demonstrate the wider implications of this sequential strategy.
Building the stages of drama: Towards a Text World Theory account of dramatic play-texts
Authors: Cruickshank Tracy , Lahey Ernestine
Published: April 2010

In this article we apply the cognitive theory of discourse known as Text World Theory to the study of one play – Tom Stoppard's Rosencrantz and Guildernstern are Dead. The result of this application is twofold. First, it extends the capabilities of Text World Theory by introducing two new world types to the framework which are necessary to enable the theory to account better for dramatic texts. Following Richard Hosley's separation of stage directions into theatrical and fictional signals, we suggest ways in which these signals may prompt readers to toggle between “staged worlds” and “fictional worlds”. Second, our paper enlarges the stylistic toolkit for the analysis of dramatic play-texts, offering a cognitively-oriented alternative to the more traditional discourse-analytical approaches to the genre.
Local Glutamate Level Dictates Adenosine A2AReceptor Regulation of Neuroinflammation and Traumatic Brain Injury
Authors: Dai Shuang-Shuang , Zhou Yuan-Guo , Li Wei , An Jian-Hong , Li Ping , Yang Nan , Chen Xing-Yun , Xiong Ren-Ping , Liu Ping , Zhao Yan , Shen Hai-Ying , Zhu Pei-Fang , Chen Jiang-Fan
Published: April 2010

During brain injury, extracellular adenosine and glutamate levels increase rapidly and dramatically. We hypothesized that local glutamate levels in the brain dictates the adenosine–adenosine A2Areceptor (A2AR) effects on neuroinflammation and brain damage outcome. Here, we showed that, in the presence of low concentrations of glutamate, the A2AR agonist 3-[4-[2-[[6-amino-9-[(2R,3R,4S,5S)-5-(ethylcarbamoyl)-3,4-dihydroxy-oxolan-2-yl]purin-2-yl]amino]ethyl]phenyl]propanoic acid (CGS21680) inhibited lipopolysaccharide (LPS)-induced nitric oxide synthase (NOS) activity of cultured microglial cells, an effect that was dependent on the protein kinase A (PKA) pathway. However, in high concentrations of glutamate, CGS21680 increased LPS-induced NOS activity in a protein kinase C (PKC)-dependent manner. Thus, increasing the local level of glutamate redirects A2AR signaling from the PKA to the PKC pathway, resulting in a switch in A2AR effects from antiinflammatory to proinflammatory. In a cortical impact model of traumatic brain injury (TBI) in mice, brain water contents, behavioral deficits, and expression of tumor necrosis factor-α, interleukin-1 mRNAs, and inducible NOS were attenuated by administering CGS21680 at post-TBI time when brain glutamate levels were low, or by administering the A2AR antagonist ZM241385 [4-(2-{[5-amino-2-(2-furyl)[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-yl]amino}ethyl)phenol] at post-TBI time when brain glutamate levels were elevated. Furthermore, pre-TBI treatment with the glutamate release inhibitor (S)-4C3HPG [(S)-4-carboxy-3-hydroxyphenylglycine] converted the debilitating effect of CGS21680 administered at post-TBI time with high glutamate level to a neuroprotective effect. This further indicates that the switch in the effect of A2AR activation in intact animals from antiinflammatory to proinflammatory is dependent on glutamate concentration. These findings identify a novel role for glutamate in modulation of neuroinflammation and brain injury via the adenosine–A2AR system.
Social Interactions Determine Postural Network Sensitivity to 5-HT
Authors: Cattaert Daniel , Delbecque Jean-Paul , Edwards Donald H. , Issa Fadi A.
Published: April 2010

The excitability of the leg postural circuit and its response to serotonin (5-HT) were studiedin vitroin thoracic nervous system preparations of dominant and subordinate male crayfishes. We demonstrate that the level of spontaneous tonic activity of depressor and levator motoneurons (MNs) (which control downward and upward movements of the leg, respectively) and the amplitude of their resistance reflex are larger in dominants than in subordinates. Moreover, we show that serotonergic neuromodulation of the postural circuit also depends on social status. Depressor and levator MN tonic firing rates and resistance reflex amplitudes were significantly modified in the presence of 10 μm5-HT in dominants but not in subordinates. Using intracellular recording from depressor MNs, we show that their input resistance was not significantly different in dominants and subordinates in control conditions. However, 5-HT produced a marked depolarization in dominants and a significantly weaker depolarization in subordinates. Moreover, in the presence of 5-HT, the amplitude of the resistance reflex and the input resistance of MNs increased in dominants and decreased in subordinates. The peak amplitude and the decay phase of unitary EPSPs triggered by sensory spikes were significantly increased by 5-HT in dominants but not in subordinates. These observations suggest that neural networks are more reactive in dominants than in subordinates, and this divergence is even reinforced by 5-HT modulation.