bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of cigarette smoke‐induced toll‐like receptor 4 expression by peroxisome proliferator‐activated receptor‐gamma agonists in bronchial epithelial cells
Authors: Yin Yan , Hou Gang , Li Er‐ran , Wang Qiu‐yue , Kang Jian 
Published: November 2013

AbstractBackground and objectiveThis study was designed to determine the effects of peroxisome proliferator‐activated receptor‐gamma (PPARγ) on airway inflammatory response to cigarette smoke (CS) exposure.MethodsFor the in vivo experiments, 50 male Wistar rats were randomly assigned to one of four groups and were exposed to CS and pretreatment with a PPARγ agonist, rosiglitazone or a vehicle (saline). PPARγ antagonist bisphenol A diglycidyl ether (BADGE) or saline was administered before rosiglitazone treatment. Leukotriene B4 (LTB4) and interleukin‐8 (IL‐8) were measured by enzyme‐linked immunosorbent assay. PPARγ and toll‐like receptor 4 (TLR4) expression levels were assessed by immunohistochemistry and real‐time polymerase chain reaction. For the in vitro experiments, human bronchial epithelial cells were stimulated with CS or phosphate buffer saline, pretreated with PPARγ agonist rosiglitazone or 15‐deoxy‐(Δ12,14)‐PG J2 before CS exposure. BADGE was administered prior to the agonist treatment. PPARγ, TLR4 and inhibitor of κB (IκBα) expression levels were assessed by Western bot.ResultsCS exposure decreased PPARγ expression, as well as increased IL‐8, LTB4 and TLR4 expression levels in bronchial epithelial cells in vivo and in vitro. Moreover, PPARγ ligands counteracted CS‐induced airway inflammation by reducing IL‐8 and LTB4 expression levels that are associated with TLR4 and nuclear factor‐kappa B (NF‐κB).ConclusionCS exposure increased the pro‐inflammatory activity of bronchial epithelial cells by affecting PPARγ expression. Moreover, PPARγ may play a significant role as a modulator of the TLR4‐dependent inflammatory pathway through NF‐κB in bronchial epithelial cells.
Respiratory syncytial virus induces leukotriene C4 synthase expression in bronchial epithelial cells
Authors: Sun Li‐hong , Chen Ai‐huan , Yang Zi‐feng , Chen Jason J. , Guan Wen‐da , Wu Jie‐ling , Qin Sheng , Zhong Nan‐shan 
Published: November 2013

AbstractBackground and objectiveRespiratory syncytial virus (RSV) results in acute wheezing in infants and is frequently associated with recurrent wheezing. Although RSV‐induced wheezing clinically resembles that of asthma, corticosteroids are not equivalently effective in RSV‐associated wheezing. The study sought to determine the mechanisms of RSV‐induced wheezing by establishing an in vitro model of RSV‐infected human bronchial epithelial cells (16‐HBEC).MethodsLeukotriene C4 synthase (LTC4S) messenger RNA (mRNA) expression in 16‐HBEC was detected using fluorescence quantitative polymerase chain reaction, and the relative level of LTC4S mRNA was expressed as quotient cycle threshold (qCt) based on the threshold cycle number value compared with that of β‐actin. Cysteinyl leukotrienes (CysLT) in culture supernatant were measured by enzyme‐linked immunosorbent assay. RSV‐infected 16‐HBEC was incubated with gradient concentration of budesonide (BUD) to assess its effects on LTC4S expression and CysLT secretion.ResultsRSV infection resulted in increased LTC4S mRNA expression between 48 and 96 h post‐infection. High level of CysLT was detected in the supernatant of RSV‐infected 16‐HBEC. BUD at concentrations of 10−10 to 10−5 mol/L did not significantly alter LTC4S mRNA expression.ConclusionsRSV infection upregulated LTC4S expression in HBEC leading to increased CysLT secretion. Such induction was not attenuated by BUD, suggesting that CysLT might contribute to the pathogenesis of RSV‐induced wheezing.
Quick and Easy One-Step Parameter Estimation in Differential Equations
Authors: Hall Peter , Ma Yanyuan 
Published: November 2013

SummaryDifferential equations are customarily used to describe dynamic systems. Existing methods for estimating unknown parameters in those systems include parameter cascade, which is a spline-based technique, and pseudo-least-squares, which is a local-polynomial-based two-step method. Parameter cascade is often referred to as a ‘one-step method’, although it in fact involves at least two stages: one to choose the tuning parameter and another to select model parameters. We propose a class of fast, easy-to-use, genuinely one-step procedures for estimating unknown parameters in dynamic system models. This approach does not need extraneous estimation of the tuning parameter; it selects that quantity, as well as all the model parameters, in a single explicit step, and it produces root-n-consistent estimators of all the model parameters. Although it is of course not as accurate as more complex methods, its speed and ease of use make it particularly attractive for exploratory data analysis.
The Bayesian Bridge
Authors: Polson Nicholas G. , Scott James G. , Windle Jesse 
Published: November 2013

SummaryWe propose the Bayesian bridge estimator for regularized regression and classification. Two key mixture representations for the Bayesian bridge model are developed: a scale mixture of normal distributions with respect to an α-stable random variable; a mixture of Bartlett–Fejer kernels (or triangle densities) with respect to a two-component mixture of gamma random variables. Both lead to Markov chain Monte Carlo methods for posterior simulation, and these methods turn out to have complementary domains of maximum efficiency. The first representation is a well-known result due to West and is the better choice for collinear design matrices. The second representation is new and is more efficient for orthogonal problems, largely because it avoids the need to deal with exponentially tilted stable random variables. It also provides insight into the multimodality of the joint posterior distribution, which is a feature of the bridge model that is notably absent under ridge or lasso-type priors. We prove a theorem that extends this representation to a wider class of densities representable as scale mixtures of beta distributions, and we provide an explicit inversion formula for the mixing distribution. The connections with slice sampling and scale mixtures of normal distributions are explored. On the practical side, we find that the Bayesian bridge model outperforms its classical cousin in estimation and prediction across a variety of data sets, both simulated and real. We also show that the Markov chain Monte Carlo algorithm for fitting the bridge model exhibits excellent mixing properties, particularly for the global scale parameter. This makes for a favourable contrast with analogous Markov chain Monte Carlo algorithms for other sparse Bayesian models. All methods described in this paper are implemented in the R package BayesBridge. An extensive set of simulation results is provided in two on-line supplemental files.
Evaluation of Erytra® fully automated analyser for Routine Use in Transfusion Laboratory
Authors: Chang C. , Brown M. , Davies L. , Pointon L. , Brown R. , Barker D. 
Published: November 2013

SUMMARYObjectiveTo evaluate efficiency and performance of Erytra® analyser in comparison to the reference platform of the NBT immunohaematology laboratory (Bio‐Rad ID‐System).BackgroundMoving to automation or semi‐automation is a major focus of transfusion centres. The Erytra® (Grifols) is a new fully automated walk‐away analyser with high volume processing capacity for pre‐transfusion testing, designed to be used with the unique 8‐column DG Gel® cards.Study Design and MethodsA total of 2201 immunohaematological tests (1041 ABO/D grouping, 1041 antibody screening, 51 antibody identification, 45 newborns (ABO/D and DAT) and 23 crossmatches were performed on 1160 donor/patient whole blood samples. Erytra®'s performance was assessed by means of a stress test replicating the routine work of a hospital laboratory.ResultsConcordant results between the Erytra® and the reference method were obtained in 2195 (99·73 %) of the tests. There were only three discrepancies out of 6246 reactions (0·05%) in ABO/D grouping, all in the reverse group which did not mislead to group identification. Of the 1041 samples screened for antibody presence, Erytra® detected all the relevant antibodies [9 not detected weak prophylactic anti‐D were determined to be clinically nonsignificant (<0·1 IU mL−1)] while Bio‐Rad ID‐System missed one anti‐e and one anti‐Jka. Concordance for D grouping, crossmatching and newborns was 100%. Results of the simulated stress test exercise highlighted the capacity of Erytra® for absorbing into 4 h workloads equivalent to 24 h of routine.ConclusionsGrifols' Erytra® analyser showed reliable high sensitivity, velocity and capacity to cope with high workload in the immunohaematology laboratory routine.
Hemolytic disease of the fetus and newborn caused by anti‐Lan
Authors: Brooks Sarah , Squires Jerry E. 
Published: November 2013

BackgroundAntibodies to the high‐incidence red blood cell (RBC) antigen Lan (Langereis) are typically immunoglobulin G and have been shown to fix complement and cause hemolysis of Lan antigen–positive RBCs. Only three cases of hemolytic disease of the fetus and newborn (HDFN) have been reported involving anti‐Lan and all have been characterized as “mild.”Case ReportA 26‐year‐old Hispanic female presented in her fifth pregnancy for routine obstetric care. Due to progressively rising anti‐Lan titers, middle cerebral artery (MCA) Dopplers were performed. At 32 weeks of gestation, the antibody titer had reached 128; the MCA Doppler indicated that fetal anemia was severe. An intrauterine transfusion with Lan antigen–negative RBCs was performed and a viable infant was delivered 25 days later.DiscussionThree cases of HDFN associated with anti‐Lan have been previously reported. While these cases have been associated with somewhat variable serologic findings, none have resulted in fetal demise or severe symptomatology requiring pre‐ or postnatal intervention other than routine phototherapy. The current report, however, suggests that in some instances anti‐Lan can result in a more severe form of HDFN requiring more aggressive prenatal therapy.ConclusionIn spite of previous case reports suggesting that anti‐Lan is associated with relatively mild HDFN, this case suggests that in some instances, this antibody can cause severe HDFN requiring prenatal intervention.
Comparison of antibody titers in donor specimens and associated AS‐1 leukoreduced donor units
Authors: Hill Elizabeth A. , Bryant Barbara J. 
Published: November 2013

BackgroundDonor units with unexpected antibodies to red blood cell (RBC) antigens have transfusion restrictions and are often discarded by collection facilities. This study examined the antibody titer reduction in AS‐1 leukoreduced RBC (LR‐RBC) units and potential acceptability of these units for unrestricted transfusions.Study Design and MethodsDonor specimens and AS‐1 LR‐RBC segment samples from donors with positive antibody screens and group O donors were analyzed. Antibody identifications were performed, and titer results from the matched serum samples and segment supernatants were compared.ResultsDuring the 5‐month study, 39 donor samples with positive antibody screens, five random group O donor samples, and the associated LR‐RBC unit segments were assessed. The median donor sample and segment supernatant titers were 4 and 1, respectively. Alloantibodies were undetectable in 28% of the donor segment supernatants. The median anti‐A and anti‐B titers in the group O donor samples were 128 and were reduced to 32 in the donor segment supernatants. All ABO and other antibodies were diluted by the AS‐1 to a titer of not more than 32.ConclusionAntibody titers in AS‐1 LR‐RBC units were significantly decreased compared to donor specimens and were lower than anti‐A and ‐B titers in group O AS‐1 LR‐RBC units, which are frequently transfused to non–group O recipients. If a “clinically significant” titer for donor alloantibodies was established, blood centers could determine eligibility of units for unrestricted transfusions. This would decrease unnecessary RBC wastage and increase units available for transfusion.
Quality assurance of asymmetric jaw alignment using 2D diode array
Authors: Kim Sun Mo , Chmielewski Renata , Abbas Ahmar , Yeung Ivan W. T. , Moseley Douglas J. 
Published: November 2013

Purpose:A method using a 2D diode array is proposed to measure the junction gap (or overlap) and dose with high precision for routine quality assurance of the asymmetric jaw alignment.Methods:The central axis (CAX) of the radiation field was determined with a 15 × 15 cm2 photon field at four cardinal collimator angles so that the junction gap (or overlap) can be measured with respect to the CAX. Two abutting fields having a field size of 15 cm (length along the axis parallel to the junction) × 7.5 cm (width along the axis perpendicular to the junction) were used to irradiate the 2D diode array (MapCHECK2) with 100 MU delivered at the photon energy of 6 MV. The collimator was slightly rotated at 15° with respect to the beam central axis to increase the number of diodes effective on the measurement of junction gap. The junction gap and dose measured in high spatial resolution were compared to the conventional methods using an electronic portal imaging device (EPID) and radiochromic film, respectively. In addition, the reproducibility and sensitivity of the proposed method to the measurements of junction gap and dose were investigated.Results:The junction gap (or overlap) and dose measured by MapCHECK2 agreed well to those measured by the conventional methods of EPID and film (the differences ranged from −0.01 to 0 cm and from −1.34% to 0.6% for the gap and dose, respectively). No variation in the repeat measurements of the junction gap was found whereas the measurements of junction dose were found to vary in quite a small range over the days of measurement (0.21%–0.35%). While the sensitivity of the measured junction gap to the actual junction gap applied was the ideal value of 1 cm/cm as expected, the sensitivity of the junction dose to the actual junction gap increased as the junction gap (or overlap) decreased (maximum sensitivity: 201.7%/cm).Conclusions:The initial results suggest that the method is applicable for a comprehensive quality assurance of the asymmetric jaw alignment.
Simple Colorimetric Trypanothione Reductase-Based Assay for High-Throughput Screening of Drugs against Leishmania Intracellular Amastigotes
Authors: van den Bogaart Erika , Schoone Gerard J. , England Paul , Faber Dorien , Orrling Kristina M. , Dujardin Jean-Claude , Sundar Shyam , Schallig Henk D. F. H. , Adams Emily R. 
Published: November 2013

ABSTRACT

Critical to the search for new anti-leishmanial drugs is the availability of high-throughput screening (HTS) methods to test chemical compounds against the relevant stage for pathogenesis, the intracellular amastigotes. Recent progress in automated microscopy and genetic recombination has produced powerful tools for drug discovery. Nevertheless, a simple and efficient test for measuring drug activity against
Leishmania
clinical isolates is lacking. Here we describe a quantitative colorimetric assay in which the activity of a
Leishmania
native enzyme is used to assess parasite viability. Enzymatic reduction of disulfide trypanothione, monitored by a microtiter plate reader, was used to quantify the growth of
Leishmania
parasites. An excellent correlation was found between the optical density at 412 nm and the number of parasites inoculated. Pharmacological validation of the assay was performed against the conventional alamarBlue method for promastigotes and standard microscopy for intracellular amastigotes. The activity of a selected-compound panel, including several anti-leishmanial reference drugs, demonstrated high consistency between the newly developed assay and the reference method and corroborated previously published data. Quality assessment with standard measures confirmed the robustness and reproducibility of the assay, which performed in compliance with HTS requirements. This simple and rapid assay provides a reliable, accurate method for screening anti-leishmanial agents, with high throughput. The basic equipment and manipulation required to perform the assay make it easy to implement, simplifying the method for scoring inhibitor assays.
Derepressed Transfer Properties Leading to the Efficient Spread of the Plasmid Encoding Carbapenemase OXA-48
Authors: Potron Anaïs , Poirel Laurent , Nordmann Patrice 
Published: November 2013

ABSTRACT

The current emergence of the carbapenemase OXA-48 among
Enterobacteriaceae
is related to the spread of a single IncL/M-type plasmid, pOXA-48a. This plasmid harbors the
bla
OXA-48
gene within a composite transposon, Tn
1999
, which is inserted into the
tir
gene, encoding a transfer inhibition protein. We showed that the insertion of Tn
1999
into the
tir
gene was involved in a higher transfer frequency of plasmid pOXA-48a. This may likely be the key factor for the successful dissemination of this plasmid.
Penetration of GSK1322322 into Epithelial Lining Fluid and Alveolar Macrophages as Determined by Bronchoalveolar Lavage
Authors: Naderer Odin J. , Rodvold Keith A. , Jones Lori S. , Zhu John Z. , Bowen Chester L. , Chen Liangfu , Dumont Etienne 
Published: November 2013

ABSTRACTGSK1322322 is a potent peptide deformylase inhibitor within vitroandin vivoactivity against multidrug-resistant skin and respiratory pathogens. This report provides plasma and intrapulmonary pharmacokinetics, safety, and tolerability of GSK1322322 after repeat (twice daily intravenous dosing for 4 days) dosing at 1,500 mg. Plasma samples were collected over the last 12-hour dosing interval of repeat dosing following the day 4 morning dose (the last dose). Bronchoalveolar lavage samples were collected once in each subject, either before or at 2 or 6 h after the last intravenous dose. Plasma area under the concentration-time curve (AUC0–τ) was 66.7 μg · h/ml, and maximum concentration of drug in serum (Cmax) was 25.4 μg/ml following repeat doses of intravenous GSK1322322. The time course of epithelial lining fluid (ELF) and alveolar macrophages (AM) mirrored the plasma concentration-time profile. The AUC0–τfor ELF and AM were 78.9 μg · h/ml and 169 μg · h/ml, respectively. The AUC0–τratios of ELF and AM to total plasma were 1.2 and 2.5, respectively. These ratios increased to 3.5 and 7.4, respectively, when unbound plasma was considered. These results are supportive of GSK1322322 as a potential antimicrobial agent for the treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. (This study has been registered atClinicalTrials.govunder registration number NCT01610388.)
Bactericidal Activity and Mechanism of Action of AZD5847, a Novel Oxazolidinone for Treatment of Tuberculosis
Authors: Balasubramanian V. , Solapure S. , Iyer H. , Ghosh A. , Sharma S. , Kaur P. , Deepthi R. , Subbulakshmi V. , Ramya V. , Ramachandran V. , Balganesh M. , Wright L. , Melnick D. , Butler S. L. , Sambandamurthy V. K. 
Published: November 2013

ABSTRACT

Treatment of tuberculosis (TB) is impaired by the long duration and complexity of therapy and the rising incidence of drug resistance. There is an urgent need for new agents with improved efficacy, safety, and compatibility with combination chemotherapies. Oxazolidinones offer a potential new class of TB drugs, and linezolid—the only currently approved oxazolidinone—has proven highly effective against extensively drug-resistant (XDR) TB in experimental trials. However, widespread use of linezolid is prohibited by its significant toxicities. AZD5847, a novel oxazolidinone, demonstrates improved
in vitro
bactericidal activity against both extracellular and intracellular
M. tuberculosis
compared to that of linezolid. Killing kinetics in broth media and in macrophages indicate that the rate and extent of kill obtained with AZD5847 are superior to those obtained with linezolid. Moreover, the efficacy of AZD5847 was additive when tested along with a variety of conventional TB agents, indicating that AZD5847 may function well in combination therapies. AZD5847 appears to function similarly to linezolid through impairment of the mycobacterial 50S ribosomal subunit. Future studies should be undertaken to further characterize the pharmacodynamics and pharmacokinetics of AZD5847 in both
in vitro
and animal models as well is in human clinical trials.
Insights into the Mode of Action of Novel Fluoroketolides, Potent Inhibitors of Bacterial Protein Synthesis
Authors: Krokidis Marios G. , Márquez Viter , Wilson Daniel N. , Kalpaxis Dimitrios L. , Dinos George P. 
Published: November 2013

ABSTRACTKetolides, the third generation of expanded-spectrum macrolides, have in the last years become a successful weapon in the endless war against macrolide-resistant pathogens. Ketolides are semisynthetic derivatives of the naturally produced macrolide erythromycin, displaying not only improved activity against some erythromycin-resistant strains but also increased bactericidal activity as well as inhibitory effects at lower drug concentrations. In this study, we present a series of novel ketolides carrying alkyl-aryl side chains at the C-6 position of the lactone ring and, additionally, one or two fluorine atoms attached either directly to the lactone ring at the C-2 position or indirectly via the C-13 position. According to our genetic and biochemical studies, these novel ketolides occupy the known macrolide binding site at the entrance of the ribosomal tunnel and exhibit lower MIC values against wild-type or mutant strains than erythromycin. In most cases, the ketolides display activities comparable to or better than the clinically used ketolide telithromycin. Chemical protection experiments usingEscherichia coliribosomes bearing U2609C or U754A mutations in 23S rRNA suggest that the alkyl-aryl side chain establishes an interaction with the U2609-A752 base pair, analogous to that observed with telithromycin but unlike the interactions formed by cethromycin. These findings reemphasize the versatility of the alkyl-aryl side chains with respect to species specificity, which will be important for future design of improved antimicrobial agents.
Meta-Analysis of the Adverse Effects of Long-Term Azithromycin Use in Patients with Chronic Lung Diseases
Authors: Li Hui , Liu Ding-Hui , Chen Lu-Lu , Zhao Qi , Yu Yan-Zhe , Ding Jing-Jing , Miao Li-Yun , Xiao Yong-Long , Cai Hou-Rong , Zhang De-Ping , Guo Yu-Biao , Xie Can-Mao 
Published: November 2013

ABSTRACT
The adverse effects of azithromycin on the treatment of patients with chronic lung diseases (CLD) were evaluated in the present study. MEDLINE and other databases were searched for relevant articles published until August 2013. Randomized controlled trials that enrolled patients with chronic lung diseases who received long-term azithromycin treatment were selected, and data on microbiological studies and azithromycin-related adverse events were abstracted from articles and analyzed. Six studies were included in the meta-analysis. The risk of bacterial resistance in patients receiving long-term azithromycin treatment was increased 2.7-fold (risk ratio [RR], 2.69 [95% confidence interval {95% CI}, 1.249, 5.211]) compared with the risk in patients receiving placebo treatment. On the other hand, the risk of bacterial colonization decreased in patients receiving azithromycin treatment (RR, 0.551 [95% CI, 0.460, 0.658]). Patients receiving long-term azithromycin therapy were at risk of increased impairment of hearing (RR, 1.168 [95% CI, 1.030, 1.325]). This analysis provides evidence supporting the idea that bacterial resistance can develop with long-term azithromycin treatment. Besides the increasingly recognized anti-inflammatory role of azithromycin used in treating chronic lung diseases, we should be aware of the potential for adverse events with its long-term use.