bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis C Virus RNA Elimination and Development of Resistance in Replicon Cells Treated with BMS-790052
Authors: Wang Chunfu , Huang Haichang , Valera Lourdes , Sun Jin-Hua , O'Boyle Donald R. , Nower Peter T. , Jia Lingling , Qiu Dike , Huang Xin , Altaf Aneela , Gao Min , Fridell Robert A. 
Published: January 2012

ABSTRACT

BMS-790052, a first-in-class hepatitis C virus (HCV) replication complex inhibitor, targeting nonstructural protein 5A (NS5A), displays picomolar to nanomolar potency against genotypes 1 to 5. This exceptional potency translated into robust anti-HCV activity in clinical studies with HCV genotype 1-infected subjects. To date, all BMS-790052-associated resistance mutations have mapped to the N-terminal region of NS5A. To further characterize the antiviral activity of BMS-790052, HCV replicon elimination and colony formation assays were performed. Replicon was cleared from genotype 1a and 1b replicon cells in a time- and dose-dependent manner. Elimination of the genotype 1a replicon required longer treatment durations and higher concentrations of BMS-790052 than those for the genotype1b replicon. Single amino acid substitutions that conferred relatively low levels of resistance were observed at early time points and at low doses. Higher doses and longer treatment durations yielded mutations that conferred greater levels of resistance, including linked amino acid substitutions. Replicon cells that survived inhibitor treatment remained fully sensitivity to pegylated alpha interferon (pegIFN-α) and other HCV inhibitors. Moreover, genotype 1a replicon elimination was markedly enhanced when pegIFN-α and BMS-790052 were combined. Resistant variants observed in this study were very similar to those observed in a multiple ascending dose (MAD) monotherapy trial of BMS-790052, validating replicon elimination studies as a model to predict clinical resistance. Insights gained from the
in vitro
anti-HCV activity and resistance profiles of BMS-790052 will be used to help guide the clinical development of this novel HCV inhibitor.
Transferable Multidrug Resistance Plasmid Carrying
cfr
Associated with
tet
(L),
ant(4
′
)-Ia
, and
dfrK
Genes from a Clinical Methicillin-Resistant Staphylococcus aureus ST125 Strain
Authors: Ruiz de Gopegui Enrique , Juan Carlos , Zamorano Laura , Pérez José L. , Oliver Antonio 
Published: January 2012

ABSTRACT

A multidrug resistance (MDR) conjugative plasmid of ca. 50 kb (designated pERGB) was detected in a linezolid and methicillin-resistant
Staphylococcus aureus
strain with sequence type 125 (ST125-MRSA-IVc). This strain was detected in two patients with chronic obstructive pulmonary disease, previously treated with multiple antimicrobials, including linezolid. pERGB was transferable by conjugation and carried the resistance genes
cfr
(oxazolidinones, phenicols, lincosamides, pleuromutilins, and streptogramin A),
ant(4
′
)-Ia
(tobramycin),
tet
(L) (tetracycline), and
dfrK
(trimethoprim). A novel genetic structure, linking all of these resistance genes for the first time, was elucidated through sequencing of a 15,259-bp fragment from pERGB. Active surveillance to prevent the dissemination of such highly concerning MDR transferable elements is needed.
MpeR Regulates the
mtr
Efflux Locus in Neisseria gonorrhoeae and Modulates Antimicrobial Resistance by an Iron-Responsive Mechanism
Authors: Mercante Alexandra Dubon , Jackson Lydgia , Johnson Paul J. T. , Stringer Virginia A. , Dyer David W. , Shafer William M. 
Published: January 2012

ABSTRACT

Previous studies have shown that the MpeR transcriptional regulator produced by
Neisseria gonorrhoeae
represses the expression of
mtrF
, which encodes a putative inner membrane protein (MtrF). MtrF works as an accessory protein with the Mtr efflux pump, helping gonococci to resist high levels of diverse hydrophobic antimicrobials. Regulation of
mpeR
has been reported to occur by an iron-dependent mechanism involving Fur (ferric uptake regulator). Collectively, these observations suggest the presence of an interconnected regulatory system in gonococci that modulates the expression of efflux pump protein-encoding genes in an iron-responsive manner. Herein, we describe this connection and report that levels of gonococcal resistance to a substrate of the
mtrCDE
-encoded efflux pump can be modulated by MpeR and the availability of free iron. Using microarray analysis, we found that the
mtrR
gene, which encodes a direct repressor (MtrR) of
mtrCDE
, is an MpeR-repressed determinant in the late logarithmic phase of growth when free iron levels would be reduced due to bacterial consumption. This repression was enhanced under conditions of iron limitation and resulted in increased expression of the
mtrCDE
efflux pump operon. Furthermore, as judged by DNA-binding analysis, MpeR-mediated repression of
mtrR
was direct. Collectively, our results indicate that both genetic and physiologic parameters (e.g., iron availability) can influence the expression of the
mtr
efflux system and modulate levels of gonococcal susceptibility to efflux pump substrates.
Leukocyte Inflammatory Responses Provoked by Pneumococcal Sialidase
Authors: Chang Yung-Chi , Uchiyama Satoshi , Varki Ajit , Nizet Victor 
Published: January 2012

ABSTRACT

Cell surface expression of sialic acid has been reported to decrease during immune cell activation, but the significance and regulation of this phenomenon are still being investigated. The major human bacterial pathogen
Streptococcus pneumoniae
causes pneumonia, sepsis and meningitis, often accompanied by strong inflammatory responses.
S. pneumoniae
expresses a sialidase (NanA) that contributes to mucosal colonization, platelet clearance, and blood-brain barrier penetration. Using wild-type and isogenic NanA-deficient mutant strains, we showed that
S. pneumoniae
NanA can desialylate the surface of human THP-1 monocytes, leading to increased ERK phosphorylation, NF-κB activation, and proinflammatory cytokine release.
S. pneumoniae
NanA expression also stimulates interleukin-8 release and extracellular trap formation from human neutrophils. A mechanistic contribution of unmasking of inhibitory Siglec-5 from
cis
sialic acid interactions to the proinflammatory effect of NanA is suggested by decreased SHP-2 recruitment to the Siglec-5 intracellular domain and RNA interference studies. Finally, NanA increased production of proinflammatory cytokines in a murine intranasal challenge model of
S. pneumoniae
pneumonia.

IMPORTANCE
Sialic acids decorate the surface of all mammalian cells and play important roles in physiology, development, and evolution. Siglecs are sialic acid-binding receptors on the surface of immune cells, many of which engage in
cis
interactions with host sialoglycan ligands and dampen inflammatory responses through transduction of inhibitory signals. Recently, certain bacterial pathogens have been shown to suppress leukocyte innate immune responses by molecular mimicry of host sialic acid structures and engagement of inhibitory Siglecs. Our present work shows that the converse can be true, i.e., that a microbial sialic acid-cleaving enzyme can induce proinflammatory responses, which are in part mediated by unmasking of an inhibitory Siglec. We conclude that host leukocytes are poised to detect and respond to microbial sialidase activity with exaggerated inflammatory responses, which could be beneficial or detrimental to the host depending on the site, stage and magnitude of infection.
Electrolytes in sick neonates – which sodium is the right answer?
Authors: King Richard I , Mackay Richard J , Florkowski Christopher M , Lynn Adrienne M 
Published: January 2012

IntroductionHypoproteinaemia leads to spuriously high-sodium values when measured by indirect ion-selective electrodes (ISE) as used in main laboratory analysers compared with direct ISE employed in point-of-care analysers (POCT). The authors, therefore, investigated the occurrence of hypoalbuminaemia and its effect on measured sodium from POCT and the main laboratory analyser of neonatal intensive-care samples.MethodSodium, in paired retrospective samples, measured by the main laboratory and neonatal unit blood-gas (POCT) analysers were compared.ResultsHypoalbuminaemia (<30 g/l) was present in 1400/2420 paired results. Sodium was higher when measured by laboratory analyser, the difference increased with decreasing albumin; sodium (laboratory – POCT)=7.6 (±1.1)–0.22 (±0.04)×albumin. A difference >3 mmol/l was present in 31% and consequently underestimated (9.4%) hyponatraemia and overestimated (3.8%) hypernatraemia.ConclusionHypoalbuminaemia is common in sick neonates and monitoring electrolytes using POCT and laboratory analysers frequently yield significantly different results with consequent misclassification. In these patients, measurement of electrolytes by direct ISE (blood-gas analyser) may be more accurate.
Systematic selection of screening participants by risk score in a chlamydia screening programme is feasible and effective
Authors: van den Broek Ingrid V F , Brouwers Elfi E H G , Götz Hannelore M , van Bergen Jan E A M , Op de Coul Eline L M , Fennema Johannes S A , Koekenbier Rik H , Pars Lydia L , van Ravesteijn Sander M , Hoebe Christian J P A 
Published: January 2012

ObjectivesSystematic screening forChlamydia trachomatisby individual invitation can be optimised by filtering participants on risk profile, excluding people at no or low risk. The authors investigated this technique in a large-scale chlamydia screening programme in the Netherlands in one rural region where relatively low prevalence was expected (<2%).MethodsInvitees were alerted by personal letter to log in tohttp://www.chlamydiatest.nland fill in an 8-item questionnaire. Only invitees with sufficient score could proceed to request a test kit. The authors investigated the effect of selection on participation, positivity and acceptability in three screening rounds and on the number needed to invite and the number needed to screen.ResultsThe selection led to exclusion of 36% of potential participants and a positivity rate of 4.8% among participants, achieving similar number needed to screen values in the rural and urban areas. Higher scores were clearly related to higher positivity rates. Persons who were excluded from participation did not have a lower response in the next round. The acceptability study revealed disappointment about exclusion of 30% of excluded participants but most approved of the screening set-up.ConclusionsSystematic selection of screening participants by risk score is feasible and successful in realising higher positivity rates. A somewhat stricter selection could be applied in the rural and urban areas of the screening programme. Multiple-item selection with a cut-off total score may work better than, more commonly used, selection by single criteria, especially in low-risk populations. Acceptability of selection is high but could still be improved by better communication on expectations.
Prescriber Monitoring for Benign Prostatic Hyperplasia Within a Family Medicine Clinic
Authors: Sherman Justin J. , Welch Ron W. , Hill T. Matthew , McEwen Corey 
Published: January 2012

Purpose: The purpose of this study was to compare prescriber monitoring for safety and efficacy of medication classes used to treat benign prostatic hyperplasia (BPH). Methods: This was a retrospective chart review of patients diagnosed with BPH who were prescribed medications within a family medicine clinic between January 2008 and August 2010. Patients were divided into those receiving nonselective and uroselective alpha-blockers, 5-alpha reductase inhibitors (5-ARIs), and combination therapy. A chart review was performed with regard to predetermined criteria to monitor how efficacy and adverse effects were assessed by providers in the clinic. Results: A general genitourinary assessment was documented most frequently for patients receiving 5-ARIs and least frequently in patients receiving nonselective alpha-blockers. A digital rectal examination was documented in 11% of patients. Prostate-specific antigen concentrations were assessed evenly across all medication classes and documented in 47% of eligible patients. However, the American Urological Association Symptom Index and quality-of-life questions were not performed on any patients, and assessments of adverse effects were not documented. Conclusion: Although prescribers in a family medicine clinic recorded a general genitourinary assessment for patients receiving BPH medications, a more standardized approach is needed.
Cell type specificity of female lung cancer associated with sulfur dioxide from air pollutants in Taiwan: An ecological study
Authors: Tseng Ching-Yu , Huang Yi-Chia , Su Shih-Yung , Huang Jing-Yang , Lai Cheng-Hsiu , Lung Chia-Chi , Ho Chien-Chang , Liaw Yung-Po 
Published: January 2012

Abstract

Background
Many studies have examined the association between air pollutants (including sulfur dioxide [SO2], carbon monoxide [CO], nitrogen dioxide [NO2], nitric oxide [NO], ozone [O3], and particulate matter < 10 μm [PM10]) and lung cancer. However, data from previous studies on pathological cell types were limited, especially for SO2 exposure. We aimed to explore the association between SO2 exposure from outdoor air pollutants and female lung cancer incidence by cell type specificity.

Methods
We conducted an ecological study and calculated annual average concentration of 6 air pollutants (SO2, CO, NO2, NO, O3, and PM10) using data from Taiwan Environmental Protection Administration air quality monitoring stations. The Poisson regression models were used to evaluate the association between SO2 and age-standardized incidence rate of female lung cancer by two major pathological types (adenocarcinoma [AC] and squamous cell carcinoma [SCC]). In order to understand whether there is a dose-response relationship between SO2 and two major pathological types, we analyzed 4 levels of exposure based on quartiles of concentration of SO2.

Results
The Poisson regression results showed that with the first quartile of SO2 concentration as the baseline, the relative risks for AC/SCC type cancer among females were 1.20 (95% confidence interval [CI], 1.04-1.37)/1.39 (95% CI, 0.96-2.01) for the second, 1.22 (95% CI, 1.04-1.43)/1.58 (95% CI, 1.06-2.37) for the third, and 1.27 (95% CI, 1.06-1.52)/1.80 (95% CI, 1.15-2.84) for the fourth quartile of SO2 concentration. The tests for trend were statistically significant for both AC and SCC at P = 0.0272 and 0.0145, respectively.

Conclusion
The current study suggests that SO2 exposure as an air pollutant may increase female lung cancer incidence and the associations with female lung cancer is much stronger for SCC than for AC. The findings of this study warrant further investigation on the role of SO2 in the etiology of SCC.
Peripheral blood gene expression: it all boils down to the RNA collection tubes
Authors: Menke Andreas , Rex-Haffner Monika , Klengel Torsten , Binder Elisabeth B , Mehta Divya 
Published: January 2012

Abstract

Background
Gene expression profiling from peripheral blood is a valuable tool for biomarker discovery in clinical studies. Different whole blood RNA collection and processing methods are highly variable and might confound comparisons of results across studies. The main aim of the study was to compare genome-wide gene expression profiles obtained from the two widely used commercially available whole blood RNA collection systems - PAXgene™ and Tempus™ tubes. Comparisons of present call rates, variances, correlations and influence of globin reduction across the two collection systems was performed using in vivo glucocorticoid stimulation in 24 peripheral blood samples from three individuals.

Results
RNA quality, yield and numbers of detected transcripts from the two RNA collection systems was comparable, with no significant differences between the tube types. Globin reduction resulted in a significant increase in present call rates (p = 8.17 × 10-5 and p = 1.95 × 10-3 in PAXgene™ and Tempus™ tubes respectively) and significant decrease in gene expression variance in both RNA collection tubes (p = 0.0025 and p = 0.041 in PAXgene™ and Tempus™ tubes respectively). Comparisons of glucocorticoid receptor-stimulated gene expression profiles between the two collection tube systems revealed an overlap of only 17 to 54%, depending on the stringency level of the statistical thresholds. This overlap increased by 1-8% when the RNA samples were processed to remove the globin mRNA.

Conclusion
RNA obtained from PAXgene™ and Tempus™ tubes was comparable in terms of quality and yield, however, detectable gene expression changes after glucocorticoid receptor stimulation were distinct, with an overlap of only up to 46% between the two collection systems. This overlap increased to 54% when the samples were depleted of globin mRNA and drastically reduced to 17-18% when only gene expression differences with a fold change greater than 2.0 were assessed. These results indicate that gene expression profiles obtained from PAXgene™ and Tempus™ differ drastically and should not be analyzed together. These data suggest that researchers must exert caution while interpreting expression profiles obtained through different RNA collection tubes.
Alterations in vasomotor systems and mechanics of resistance-sized mesenteric arteries from SHR and WKY male rats following in vivo testosterone manipulation
Authors: Toot Jonathan D , Reho John J , Ramirez Rolando J , Novak Jacqueline , Ely Daniel L 
Published: January 2012

Abstract

Background
Testosterone (T) and the sympathetic nervous system each contribute to the pathology of hypertension. Altered blood vessel reactivity is also associated with the pathology of high blood pressure. The purpose of this study was to examine the effects of T manipulation in the regulation of resistance-sized blood vessel reactivity.

Methods
Adult spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) male rats at 8 weeks of age were used. The rats were divided into groups consisting of gonadally intact controls (CONT), castrate with sham implant (CAST) and castrate with T implant (CAST + T) (n = 6 to 12 per group). Following a short-term period of T treatment (approximately 4 weeks), plasma norepinephrine (NE) and plasma T were assessed by performing high-performance liquid chromatography and RIA, respectively. Resistance-sized mesenteric artery reactivity was assessed on a pressurized arteriograph for myogenic reactivity (MYO), phenylephrine (PE) responsiveness and passive structural mechanics.

Results
SHR and WKY males exhibited similar physiological trends in T manipulation, with castration significantly lowering plasma T and NE and T replacement significantly increasing plasma T and NE. T manipulation in general resulted in significant alterations in MYO of second-order mesenteric arteries, with T replacement decreasing MYO in SHR (P < 0.05) compared to CONT, T replacement increasing MYO, and CAST decreasing MYO in WKY rats (P < 0.001) compared to CONT rats. Additionally, PE-induced constriction was significantly altered in both strains following T treatment, with the effective concentration of PE to constrict the vessel to 50% of the total diameter significantly increased in the CAST + T SHR compared to CONT (P < 0.05). Comparisons of passive structural mechanics between SHR and WKY treatment groups indicated in SHR a significantly increased wall-to-lumen ratio and decreased circumferential wall stress compared to WKY treatment groups.

Conclusions
These data suggest that T and NE are involved in a complex interaction with both myogenic reactivity and structural alterations of resistance-sized blood vessels and that these factors likely contribute to the development and maintenance of hypertension.
Spinel Cobalt Oxide Catalyzed Controlled Hydration of Aromatic Nitriles
Authors: Gangarajula Yuvaraj , Gopal Buvaneswari 
Published: January 2012

Abstract
Selective hydration of aromatic nitriles to their respective amides has been achieved in the presence of spinel cobalt oxide, Co3O4 as a heterogeneous catalyst. Higher yields of the products in shorter duration have been accomplished under hydrothermal condition compared to thermal refluxing.
pH-Responsive Optical Modulation of Chemically Reduced Graphene through Noncovalent Interaction with Poly(acrylic acid)
Authors: Lee Jung Yup , In Insik 
Published: January 2012

Abstract
pH-responsive chemically reduced graphene/poly(acrylic acid) (PAA) assembly is simply formulated through noncovalent interaction. Graphene/PAA assembly shows optical absorbance change depending on pH of the solution. Structural rearrangement of graphene/PAA assembly might contribute this optical modulation at different pH through either “hydrophobic interaction dominating” mode in strongly acidic medium or “charge repulsion dominating” mode in strongly basic medium.
Isotope Ratio Analysis of Individual Plutonium and Uranium–Plutonium Mixed Oxide Particles by Thermal Ionization Mass Spectrometry with a Continuous Heating Method
Authors: Suzuki Daisuke , Saito-Kokubu Yoko , Lee Chi-Gyu , Esaka Fumitaka , Magara Masaaki , Kimura Takaumi 
Published: January 2012

Abstract
Isotope ratio analysis of individual plutonium and uranium–plutonium mixed oxide (MOX) particles was performed using a combination of single particle transfer and thermal ionization mass spectrometry (TIMS) with a continuous heating method, namely the particles were measured without any chemical treatment. Accurate values were obtained for all isotope ratios of the individual particles prepared from standard solution. As a consequence, it is confirmed that the combination method is useful for isotope ratio analysis of individual plutonium and MOX particles.
Alumina-on-alumina hip implants
Authors: Affatato S. , Traina F. , De Fine M. , Carmignato S. , Toni A. 
Published: January 2012

Alumina–alumina bearings are among the most resistant to wear in total hip replacement. Examination of their surfaces is one way of comparing damage caused by wear of hip joints simulated in vitro to that seen in explanted bearings. The aim of this study was to determine whether second-generation ceramic bearings exhibited a better pattern of wear than those reported in the literature for first-generation bearings. We considered both macro- and microscopic findings.We found that long-term alumina wear in association with a loose acetabular component could be categorised into three groups. Of 20 specimens, four had ‘low wear’, eight ‘crescent wear’ and eight ‘severe wear’, which was characterised by a change in the physical shape of the bearing and a loss of volume. This suggests that the wear in alumina–alumina bearings in association with a loose acetabular component may be variable in pattern, and may explain, in part, why the wear of a ceramic head in vivo may be greater than that seen after in vitro testing.
Retention of forearm plates
Authors: Clement N. D. , Yousif F. , Duckworth A. D. , Teoh K. H. , Porter D. E. 
Published: January 2012

Most surgeons favour removing forearm plates in children. There is, however, no long-term data regarding the complications of retaining a plate. We present a prospective case series of 82 paediatric patients who underwent plating of their forearm fracture over an eight-year period with a minimum follow-up of two years. The study institution does not routinely remove forearm plates. A total of 116 plates were used: 79 one-third tubular plates and 37 dynamic compression plates (DCP). There were 12 complications: six plates (7.3%) were removed for pain or stiffness and there were six (7.3%) implant-related fractures. Overall, survival of the plates was 85% at 10 years. Cox regression analysis identified radial plates (odds ratio (OR) 4.4, p = 0.03) and DCP fixation (OR 3.2, p = 0.02) to be independent risk factors of an implant-related fracture. In contrast ulnar plates were more likely to cause pain or irritation necessitating removal (OR 5.6, p = 0.04). The complications associated with retaining a plate are different, but do not occur more frequently than the complications following removal of a plate in children.