Efficacies of the new Paclitaxel-eluting Coroflex Please™ Stent in percutaneous coronary intervention; comparison of efficacy between Coroflex Please™ and Taxus™ (ECO-PLEASANT) trial: study rationale and design

<p>Abstract</p> <p>Background</p> <p>Previous randomized trials have showed the superiority of Paclitaxel-eluting stent over bare metal stent in angiographic and clinical outcomes. Coroflex Please™ stent is a newly developed drug eluting stent using the Coroflex™ stent platform combined with the drug paclitaxel contained in a polymer coating. PECOPS I trial, one-arm observational study, showed that the clinical and angiographic outcomes of Coroflex Please™ stent were within the range of those of Taxus, the 1^stgeneration paclitaxel-eluting stent (PES). However, there have been no studies directly comparing the Coroflex Please™ stent with the Taxus Liberte™ stent that is the newest version of Taxus. Therefore, prospective, randomized trial is required to demonstrate the non-inferiority of Coroflex Please™ stent compared with Taxus Liberte™ stent in a head-to-head manner.</p> <p>Methods</p> <p>In the comparison of Efficacy between COroflex PLEASe™ ANd Taxus™ stent(ECO-PLEASANT) trial, approximately 900 patients are being prospectively and randomly assigned to the either type of Coroflex Please™ stent and Taxus Liberte™ stent via web-based randomization. The primary endpoint is clinically driven target vessel revascularization at 9 months. The secondary endpoints include major cardiac adverse events, target vessel failure, stent thrombosis and angiographic efficacy endpoints.</p> <p>Discussion</p> <p>The ECO-PLEASANT trial is the study not yet performed to directly compare the efficacy and safety of the Coroflex Please™ versus Taxus Liberte™ stent. On the basis of this trial, we will be able to find out whether the Coroflex Please™ stent is non-inferior to Taxus Liberte™ stent or not.</p> <p>Trial registration</p> <p>ClinicalTrials.gov number, NCT00699543.</p

Dynamics of Endoreplication during Drosophila Posterior Scutellar Macrochaete Development

Endoreplication is a variant type of DNA replication, consisting only of alternating G1 and S phases. Many types of Drosophila tissues undergo endoreplication. However, the timing and the extent to which a single endocycling macrochaete undergoes temporally programmed endoreplication during development are unclear. Here, we focused on the dynamics of endoreplication during posterior scutellar (pSC) macrochaete development. Quantitative analyses of C values in shaft cells and socket cells revealed a gradual rise from 8C and 4C at 8 hours after pupal formation (APF) to 72C and 24C at 29 hours APF, respectively. The validity of the values was further confirmed by the measurement of DNA content with a confocal laser microscope. BrdU incorporation assays demonstrated that shaft cells undergo four rounds of endoreplication from 18 to 29.5 hours APF. In contrast, socket cells undergo two rounds of endoreplication during the same period. Statistical analyses showed that the theoretical C values, based on BrdU assays, nearly coincide with the actually measured C values in socket cells, but not in shaft cells after 22 hours APF. These analyses suggest that socket cells undergo two rounds of endoreplication. However, the mechanism of endoreplication in the shaft cells may change from 22 hours APF, suggesting the possibility that shaft cells undergo two or four rounds of endoreplication during the periods. We also found that the timing of endoreplication differs, depending on the type of macrochaete. Moreover, endocycling in shaft cells of both the left and right sides of pSC bristle lineages occurs in the same pattern, indicating that the process is synchronized for specific types of macrochaete. Our findings suggest that endocycling in macrochaete cell lineages can be a model for understanding mechanisms of endoreplication at the single-cell level

A Measurement of Rb using a Double Tagging Method

The fraction of Z to bbbar events in hadronic Z decays has been measured by the OPAL experiment using the data collected at LEP between 1992 and 1995. The Z to bbbar decays were tagged using displaced secondary vertices, and high momentum electrons and muons. Systematic uncertainties were reduced by measuring the b-tagging efficiency using a double tagging technique. Efficiency correlations between opposite hemispheres of an event are small, and are well understood through comparisons between real and simulated data samples. A value of Rb = 0.2178 +- 0.0011 +- 0.0013 was obtained, where the first error is statistical and the second systematic. The uncertainty on Rc, the fraction of Z to ccbar events in hadronic Z decays, is not included in the errors. The dependence on Rc is Delta(Rb)/Rb = -0.056*Delta(Rc)/Rc where Delta(Rc) is the deviation of Rc from the value 0.172 predicted by the Standard Model. The result for Rb agrees with the value of 0.2155 +- 0.0003 predicted by the Standard Model.Comment: 42 pages, LaTeX, 14 eps figures included, submitted to European Physical Journal

Immune Events Associated with High Level Protection against Schistosoma japonicum Infection in Pigs Immunized with UV-Attenuated Cercariae

BACKGROUND: The vaccination of radiation-attenuated Schistosoma japonicum cercariae can induce effective protection in artiodactyl, but the immune events related to protective immunity are not fully understood. To provide a paradigm for a human recombinant antigen vaccine, we have undertaken a vaccination and challenge experiment in pigs, which was recognized as an appropriate animal model in this type of study because of their similarity to human in immunology, and investigated the relative immune events induced by the radiation-attenuated S. japonicum cercariae. METHODS AND FINDINGS: We found that pigs immunized once with 400 µw UV-irradiated cercariae exhibited 63.84% and 71.82% reductions in worm burden and hepatic eggs respectively. Protective immunity in vaccinated pigs was associated with high level productions of IgM, total IgG, IgG1 and IgG2; IgG2 was significantly increased in the acute infection. IFN-γ levels could be elicited by immunization. At week 6 post-infection, IFN-γ, IL-4 and IL-10 levels also showed a dramatic rise synchronously in vaccinated pigs. Moreover, the granzyme b, nk-lysin, ifnγ, il4 and il10 mRNA levels in early skin-draining lymph nodes of immunized pigs were higher than those in pigs with non-irradiated cercariae infection. In addition, cytotoxicity-related genes in the mesenteric lymph nodes were significantly upregulated in vaccinated pigs in the acute infection. CONCLUSION/SIGNIFICANCE: Our results demonstrated that IFN-γ and IgG2 antibody production, as well as genes related to cytotoxicity are associated with the high level protection induced by UV-irradiated Schistosoma japonicum vaccine. These findings indicated that optimal vaccination against S. japonicum required the induction of IFN-γ, IgG2 antibody related to Th1 responses and cytotoxicity effect

Measurement of the B+ and B-0 lifetimes and search for CP(T) violation using reconstructed secondary vertices

The lifetimes of the B+ and B-0 mesons, and their ratio, have been measured in the OPAL experiment using 2.4 million hadronic Z(0) decays recorded at LEP. Z(0) --> b (b) over bar decays were tagged using displaced secondary vertices and high momentum electrons and muons. The lifetimes were then measured using well-reconstructed charged and neutral secondary vertices selected in this tagged data sample. The results aretau(B+) = 1.643 +/- 0.037 +/- 0.025 pstau(Bo) = 1.523 +/- 0.057 +/- 0.053 pstau(B+)/tau(Bo) = 1.079 +/- 0.064 +/- 0.041,where in each case the first error is statistical and the second systematic.A larger data sample of 3.1 million hadronic Z(o) decays has been used to search for CP and CPT violating effects by comparison of inclusive b and (b) over bar hadron decays, No evidence fur such effects is seen. The CP violation parameter Re(epsilon(B)) is measured to be Re(epsilon(B)) = 0.001 +/- 0.014 +/- 0.003and the fractional difference between b and (b) over bar hadron lifetimes is measured to(Delta tau/tau)(b) = tau(b hadron) - tau((b) over bar hadron)/tau(average) = -0.001 +/- 0.012 +/- 0.008

Characterization of the Fungal Microbiota (Mycobiome) in Healthy and Dandruff-Afflicted Human Scalps

The human scalp harbors a vast community of microbial mutualists, the composition of which is difficult to elucidate as many of the microorganisms are not culturable using current culture techniques. Dandruff, a common scalp disorder, is known as a causative factor of a mild seborrheic dermatitis as well as pityriasis versicolor, seborrheic dermatitis, and atopic dermatitis. Lipophilic yeast Malassezia is widely accepted to play a role in dandruff, but relatively few comprehensive studies have been reported. In order to investigate fungal biota and genetic resources of dandruff, we amplified the 26S rRNA gene from samples of healthy scalps and dandruff-afflicted scalps. The sequences were analyzed by a high throughput method using a GS-FLX 454 pyrosequencer. Of the 74,811 total sequence reads, Basidiomycota (Filobasidium spp.) was the most common phylum associated with dandruff. In contrast, Ascomycota (Acremonium spp.) was common in the healthy scalps. Our results elucidate the distribution of fungal communities associated with dandruff and provide new avenues for the potential prevention and treatment of dandruff

A comparison of the Charlson comorbidity index derived from medical records and claims data from patients undergoing lung cancer surgery in Korea: a population-based investigation

<p>Abstract</p> <p>Background</p> <p>Calculating the Charlson comorbidity index (CCI) from medical records is a time-consuming and expensive process. The objectives of this study are to 1) measure agreement between medical record and claims data for CCI in lung cancer patients and 2) predict health outcomes of lung cancer patients based on CCIs from both data sources.</p> <p>Methods</p> <p>We studied 392 patients who underwent surgery for pathologic stages I-III of lung cancer. The kappa value was used to measure the agreement between the 17 comorbidities of the CCI prevalence obtained from medical records and claims data. Multiple linear regression analyses were used to evaluate the relationships between CCI and length of stay and reimbursement cost.</p> <p>Results</p> <p>Out of 17 comorbidities identified in the Charlson comorbidity index, ten had a higher prevalence, four had a lower prevalence and three had a similar prevalence in claims data to those of medical records. The kappa values calculated from the two databases ranged from 0.093 to 0.473 for nine comorbidities. In predicting length of stay and reimbursement cost after surgical resection for lung cancer patients, the CCI scores derived from both the medical records and claims data were not statistically significant.</p> <p>Conclusions</p> <p>Poor agreement between medical record data and claims data may result from different motivations for collecting data. Further studies are needed to determine an appropriate method for predicting health outcomes based on these data sources.</p

The Structure of the Chemokine Receptor CXCR1 in Phospholipid Bilayers and Interactions with IL-8

CXCR1 is one of two high-affinity receptors for the CXC chemokine interleukin-8 (IL-8), a major mediator of immune and inflammatory responses implicated in many disorders, including tumor growth(1-3). IL-8, released in response to inflammatory stimuli, binds to the extracellular side of CXCR1. The ligand-activated intracellular signaling pathways result in neutrophil migration to the site of inflammation(2). CXCR1 is a class-A, rhodopsin-like G-protein-coupled receptor (GPCR), the largest class of integral membrane proteins responsible for cellular signal transduction and targeted as drug receptors(4-7). Despite its importance, its molecular mechanism is poorly understood due to the limited structural information available. Recently, structure determination of GPCRs has advanced by tailoring the receptors with stabilizing mutations, insertion of the protein T4 lysozyme and truncations of their amino acid sequences(8), as well as addition of stabilizing antibodies and small molecules(9) that facilitate crystallization in cubic phase monoolein mixtures(10). The intracellular loops of GPCRs are critical for G-protein interactions(11) and activation of CXCR1 involves both N-terminal residues and extracellular loops(2,12,13). Our previous NMR studies indicate that IL-8 binding to the N-terminal residues is mediated by the membrane, underscoring the importance of the phospholipid bilayer for physiological activity(14). Here we report the three-dimensional structure of human CXCR1 determined by NMR spectroscopy. The receptor is in liquid crystalline phospholipid bilayers, without modification of its amino acid sequence and under physiological conditions. Features important for intracellular G-protein activation and signal transduction are revealed

Working Memory Impairment in Fibromyalgia Patients Associated with Altered Frontoparietal Memory Network

BACKGROUND: Fibromyalgia (FM) is a disorder characterized by chronic widespread pain and frequently associated with other symptoms. Patients with FM commonly report cognitive complaints, including memory problem. The objective of this study was to investigate the differences in neural correlates of working memory between FM patients and healthy subjects, using functional magnetic resonance imaging (MRI). METHODOLOGY/PRINCIPAL FINDINGS: Nineteen FM patients and 22 healthy subjects performed an n-back memory task during MRI scan. Functional MRI data were analyzed using within- and between-group analysis. Both activated and deactivated brain regions during n-back task were evaluated. In addition, to investigate the possible effect of depression and anxiety, group analysis was also performed with depression and anxiety level in terms of Beck depression inventory (BDI) and Beck anxiety inventory (BAI) as a covariate. Between-group analyses, after controlling for depression and anxiety level, revealed that within the working memory network, inferior parietal cortex was strongly associated with the mild (r = 0.309, P = 0.049) and moderate (r = 0.331, P = 0.034) pain ratings. In addition, between-group comparison revealed that within the working memory network, the left DLPFC, right VLPFC, and right inferior parietal cortex were associated with the rating of depression and anxiety? CONCLUSIONS/SIGNIFICANCE: Our results suggest that the working memory deficit found in FM patients may be attributable to differences in neural activation of the frontoparietal memory network and may result from both pain itself and depression and anxiety associated with pain

Scrape Off Layer (SOL) transport and filamentary characteristics in high density tokamak regimes

A detailed cross-device investigation on the role of filamentary dynamics in high density regimes has been performed within the EUROfusion framework comparing ASDEX Upgrade (AUG) and TCV tokamaks. Both devices have run density ramp experiments at different levels of plasma current, keeping toroidal field or q95 constant in order to disentangle the role of parallel connection length and the current. During the scan at constant toroidal field, in both devices SOL profiles tend to develop a clear Scrape Off Layer (SOL) density shoulder at lower edge density whenever current is reduced. The different current behavior is substantially reconciled in terms of edge density normalized to Greenwald fraction. During the scan at constant q95 AUG exhibits a similar behaviour whereas in TCV no signature of upstream profile modification has been observed at lower level of currents. The latter behaviour has been ascribed to the lack of target density roll-over. The relation between upstream density profile modification and detachment condition has been investigated. For both devices the relation between blob-size and SOL density e-folding length is found independent of the plasma current, with a clear increase of blob-size with edge density normalized to Greenwald fraction observed. ASDEX Upgrade has also explored the filamentary behaviour in H-Mode. The experiments on AUG focused on the role of neutrals, performing discharges with and without the cryogenic pumps, highlighting how large neutral pressure not only in the divertor but at the midplane is needed in order to develop a H-Mode SOL profile shoulder in AUG