bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Fluoroscopy and Ultrasound Guidance for Sacroiliac Joint Injection in Patients with Chronic Low Back Pain
Authors: Soneji Neilesh , Bhatia Anuj , Seib Rachael , Tumber Paul , Dissanayake Melanie , Peng Philip W.H.
Published: May 2015

Background and Objectives

Sacroiliac joint (SIJ) arthritis is a common cause of chronic mechanical low back pain (LBP) that is often treated with injection of local anesthetic and steroids. Ultrasound (US) has emerged as a viable alternative to fluoroscopy (FL) to guide SIJ injections; however, few studies have compared these modalities. In this prospective randomized, controlled trial, we compared both accuracy and efficacy of US and FL guidance for SIJ injections.

Methods

Forty patients with chronic moderate‐to‐severe LBP secondary to SIJ arthritis were randomized to receive US‐ or FL‐guided unilateral SIJ injections. Primary outcomes included pain at 1 month measured by numerical rating scale (NRS) scores. Secondary outcomes included NRS scores at 24 hours, 72 hours, 1 week, and 3 months after injection, physical functioning at 1 month after the procedure, procedure time, incidence of intra‐articular and peri‐articular needle placement, patient discomfort, overall patient satisfaction, and daily opioid consumption.

Results

There was no significant difference in NRS pain scores between the 2 groups at 1 month or at any other follow‐up points. A significant reduction from baseline mean NRS scores was observed in both groups at 1 month after injection (US 22.7%, P = 0.025; FL 37.3%, P < 0.001). There was no significant difference in procedure‐related variables, physical functioning, discomfort, opioid utilization, and patient satisfaction between the 2 groups.

Conclusions

Ultrasound‐guided SIJ injection with fluoroscopic confirmation has similar accuracy and efficacy to fluoroscopy alone for SIJ injections in patients with chronic low back pain secondary to SIJ arthritis.
Understanding and Reducing Inconsistency in Seatbelt‐Use Decisions: Findings from a Cardinal Decision Issue Perspective
Authors: Alattar Laith , Yates J. Frank , Eby David W. , LeBlanc David J. , Molnar Lisa J.
Published: May 2015

This article has two aims. The first is to present results that partly explain why some automobile drivers choose to use their seatbelts only part time, thereby exposing themselves to unnecessary risk. The second is to offer and illustrate the “cardinal decision issue perspective”(1) as a tool for guiding research and development efforts that focus on complex real‐life decision behaviors that can entail wide varieties of risk, including but not limited to inconsistent seatbelt use. Each of 24 young male participants drove an instrumented vehicle equipped to record continuously seatbelt use as well as other driving data. After all trips were finished, each participant completed an interview designed to reconstruct how he made randomly selected seatbelt‐use decisions under specified conditions. The interview also examined whether and how drivers established “decision policies” regarding seatbelt use. Such policies were good predictors of inconsistent seatbelt use. Drivers who had previously adopted policies calling for consistent seatbelt use were significantly more likely than others to actually drive belted. Meta‐decisions about seatbelt policy adoption appeared to rest on factors such as whether the driver had ever been asked to consider selecting a policy. Whether a driver made an ad hoc, on‐the‐spot seatbelt‐use decision was associated with a perceived need to make such a decision. Finally, participants with full‐time policies were especially likely to deploy their seatbelts by default, without recognizing the need to decide about belt use on a trip‐by‐trip basis. We end with recommendations for reducing inconsistencies in seatbelt use in actual practice.
Fiscal Transfers in a Monetary Union with Exit Option
Authors: Hefeker Carsten , Neugart Michael
Published: May 2015

It is widely debated whether a monetary union has to be accompanied by a fiscal transfer scheme to accommodate asymmetric shocks. We build a model of a monetary union with a central bank and two heterogeneous countries that are linked by a fiscal transfer scheme with repercussions on monetary policy. A central bank aiming at securing the existence of a monetary union in the presence of asymmetric shocks has to compensate single countries for the tax distortions arising from fiscal transfers. Monetary policy may become more expansionary or restrictive depending on asymmetries between member countries' inflation aversion and exit costs.
Mixed Frequency Structural Vector Auto-Regressive Models
Authors: Foroni Claudia , Marcellino Massimiliano
Published: May 2015

A mismatch between the timescale of a structural vector auto-regressive model and that of the time series data used for its estimation can have serious consequences for identification, estimation and interpretation of the impulse response functions. However, the use of mixed frequency data, combined with a proper estimation approach, can alleviate the temporal aggregation bias, mitigate the identification issues and yield more reliable responses to shocks. The problems and possible remedy are illustrated analytically and with both simulated and actual data.
A Supersymmetric AKNS Problem and Its Darboux‐Bäcklund Transformations and Discrete Systems
Authors: Xue Lingling , Liu Q. P.
Published: May 2015

In this paper, we consider a supersymmetric AKNS spectral problem. Two elementary and a binary Darboux transformations are constructed. By means of reductions, Darboux and Bäcklund transformations are given for the supersymmetric modified Korteweg‐de Vries, sinh‐Gordon, and nonlinear Schrödinger equations. These Darboux and Bäcklund transformations are adopted for the constructions of integrable discrete super systems, and both semidiscrete and fully discrete systems are presented. Also, the continuum limits of the relevant discrete systems are worked out.
Rights for All: A Response to Blau
Authors: Esparza Louis Edgar
Published: May 2015

Most of the world's nations have revised their constitutions to protect the human rights of their citizens. Yet there has been no national discussion in this country to write human rights into our own constitution. Building on Blau's (2015) call to action, this work explores ways in which sociologists can align the principles of our profession to the advancement of human society and the protection of human rights.
Damage Monitoring of External Patch Repairs with Guided Ultrasonic Waves
Authors: Pavlopoulou S. , Worden K. , Soutis C.
Published: May 2015

A composite panel with a pre‐introduced hole was repaired with an external repair patch and tested under tension–tension fatigue. X‐ray radiography and microscopic analysis were employed to assess the developed damage which appeared first in the form of axial splitting at the hole and propagation until the final patch debonding. Piezoelectric transducers bonded on the top and bottom of the tested surface were utilised in‐phase and out‐of‐phase in order to excite separately the symmetric and antisymmetric fundamental Lamb wave modes. The estimation of each mode's arrival time was performed through the Akaike information criterion which indicated that only the excitation of the antisymmetric mode was successful due to the possible corruption of the symmetric mode with the shear horizontal mode. The study investigated the problem of inadequate training data set that resulted in a negative Mahalanobis squared distance after outlier analysis application. The study suggested a pseudoinverse approach for the inverse of the covariance matrix and a reduction in the selected feature through the principal component analysis and the isolation of the most representative principal components. Finally outlier analysis was applied, which successfully represented the condition of the structural integrity.
Detection of monoclonality in intestinal lymphoma with polymerase chain reaction for antigen receptor gene rearrangement analysis to differentiate from enteritis in dogs
Authors: Ohmura S. , Leipig M. , Schöpper I. , Hergt F. , Weber K. , Rütgen B. C. , Tsujimoto H. , Hermanns W. , Hirschberger J.
Published: May 2015

The diagnosis of canine intestinal lymphoma by morphological examination is challenging, especially when endoscopic tissue specimens are used. The utility of detection of antigen receptor gene rearrangement by polymerase chain reaction (PARR) in canine lymphoma has been well established, but its usefulness to distinguish enteritis and intestinal lymphoma remains unclear. In this retrospective study we assessed clonality of 29 primary canine intestinal lymphoma, 14 enteritis and 15 healthy control cases by PARR analysis, using formalin‐fixed, paraffin‐embedded full‐thickness tissue specimens. We could detect monoclonal rearrangements in 22 of 29 canine intestinal lymphomas [76%; 95% confidence interval (CI) 56–90%] and polyclonal rearrangements in all of the enteritis and healthy control cases (100%; CI 88–100%). We revealed a predominance of T‐cell phenotype compared to B‐cell phenotype (85%; CI 65–96% and 15%; CI 4–35%, respectively). We showed that PARR analysis contributes to differentiation of canine intestinal lymphoma from enteritis and to phenotyping of lymphomas.
Characteristics of Rayleigh–Bénard Convection in a Rectangular Channel With an Inner Hot Circular Cylinder
Authors: Choi Changyoung , Yeong Ha Man , Sik Yoon Hyun
Published: May 2015

The immersed boundary method (IBM) was used for three-dimensional numerical simulations, and the results for natural convection in a rectangular channel with an inner hot circular cylinder are presented. This simulation used Rayleigh numbers spanning 3 orders of magnitude, from 1×103 to 1×106. The Prandtl number considered in this study was 0.7. We investigated the effects of the inner cylinder's radius on the thermal convection and heat transfer in the space between the cylinder and rectangular channel. A map of the thermal and flow regimes is presented as a function of the cylinder's radius and the Rayleigh number.
Analysis and Design of a Passive Steering Mechanism for a Pedaled, Self-Balanced Unicycle
Authors: Huang Chun-Feng , Hong Jian-Hao , Yeh T.-J.
Published: May 2015

In this paper, a pedaled, self-balanced vehicle named Legway, is developed. The vehicle is structurally similar to a pedaled unicycle but uses a brushless DC (BLDC) hub motor as its main driving wheel. It is intended that the unstable longitudinal dynamics of the vehicle is stabilized by a feedback control system, but the lateral balancing and steering are manually controlled by the rider via a passive steering mechanism. This study is first devoted to the dynamic modeling of the steering mechanism. It is shown from analyzing the model that there is a critical speed beyond which the unicycle becomes open-loop stable in the lateral direction so that the rider can turn the handle to steer the unicycle as the conventional bicycle. The dynamic model is then used for conducting simulations for selecting appropriate design parameters. An experimental prototype is constructed based on the analysis result and the steering performance is experimentally verified.
Assessment of Offshore Wind Energy Projects in Denmark. A Comparative Study With Onshore Projects Based on Regulatory Real Options
Authors: Iniesta José Balibrea , Barroso Manuel Monjas
Published: May 2015

There is a gap in the literature on the assessment of renewable energy projects regarding the role of regulatory real options (RROs) that do not depend entirely on the project promoter and yet affect the value of the project. This paper provides a methodology for evaluating investments in offshore wind generation in Denmark, based on the use of this type of options. The main results show that these RROs held by the administration, decrease the value of these renewable generation projects in Denmark. This confirms previous research for onshore generation in the same country.
Prototype Testing of a Centrifugal Particle Receiver for High-Temperature Concentrating Solar Applications
Authors: Wu Wei , Trebing David , Amsbeck Lars , Buck Reiner , Pitz-Paal Robert
Published: May 2015

A novel concept of a particle receiver for high-temperature solar applications was developed and evaluated in the present work. The so-called Centrifugal Particle Receiver (CentRec) uses small bauxite particles as absorber, heat transfer, and storage medium at the same time. Due to advantageous optical and thermal properties, the particles can be heated up to 1000 °C without sintering in the storage. High thermal efficiencies at high outlet temperatures are expected indicating a promising way for cost reduction in solar power tower applications. A 15kWth prototype was designed, built, and tested in order to demonstrate the feasibility and potential of the proposed concept. Extensive high flux experiments were conducted, investigating the thermal receiver performance and efficiency. For an input flux of 670 kW m−2, the target outlet temperature of 900 °C at a receiver efficiency of about 75% was successfully demonstrated.
Numerical Simulation of Transient Three-Dimensional Temperature and Kerf Formation in Laser Fusion Cutting
Authors: Kheloufi Karim , Hachemi Amara El , Benzaoui Ahmed
Published: May 2015

In the present study, a three-dimensional transient numerical model was developed to study the temperature field and cutting kerf shape during laser fusion cutting. The finite volume model has been constructed, based on the Navier–Stokes equations and energy conservation equation for the description of momentum and heat transport phenomena, and the volume of fluid (VOF) method for free surface tracking. The Fresnel absorption model is used to handle the absorption of the incident wave by the surface of the liquid metal, and the enthalpy-porosity technique is employed to account for the latent heat during melting and solidification of the material. To model the physical phenomena occurring at the liquid film/gas interface, including momentum/heat transfer, a new approach is proposed which consists of treating friction force, pressure force applied by the gas jet, and the heat absorbed by the cutting front surface as source terms incorporated into the governing equations. All these physics are coupled and solved simultaneously in fluent CFD®. The main objective of using a transient phase change model in the current case is to simulate the dynamics and geometry of a growing laser-cutting generated kerf until it becomes fully developed. The model is used to investigate the effect of some process parameters on temperature fields and the formed kerf geometry.
Resputtering effect during MgO buffer layer deposition by magnetron sputtering for superconducting coated conductors
Authors: Xiao Shaozhu , Feng Feng , Shi Kai , Deng Shutong , Qu Timing , Zhu Yuping , Lu Hongyuan , Huang Rongxia , Han Zhenghe
Published: May 2015

In this study, MgO thin films were deposited by radio-frequency magnetron sputtering. The film thickness in the deposition area directly facing the target center obviously decreased compared with that in other areas. This reduction in thickness could be attributed to the resputtering effect resulting from bombardment by energetic particles mainly comprising oxygen atoms and negative oxygen ions. The influences of deposition position and sputtering pressure on the deposition rate were investigated. Resputtering altered the orientation of the MgO film from (111) to (001) when the film was deposited on a single crystal yttria-stabilized zirconia substrate. The density distribution of energetic particles was calculated on the basis of the measured thicknesses of the MgO films deposited at different positions. The divergence angle of the energetic particle flux was estimated to be approximately 15°. The energetic particle flux might be similar to the assisting ion flux in the ion beam assisted deposition process and could affect the orientation of the MgO film growth.
Milk needs Orai1
Authors: Prabakaran Sudhakaran
Published: May 2015

The store-operated calcium channel Orai1 is required for both the transport of calcium into milk and the ejection of milk during lactation.
Too stimulated to suck
Authors: Ferrarelli Leslie K.
Published: May 2015

Some insecticides activate TRP channels to overstimulate mechanosensory neurons to impair insect mouth movements and prevent feeding.
Which receptor underlies chronic pain?
Authors: Kelner Katrina L. , Gough Nancy R.
Published: May 2015

Finding that nicotinic receptors containing the α6 subunit, but not the α4, inhibit chronic pain points to a new set of potential therapeutic drugs.
Neurons promote glioma growth
Authors: Gough Nancy R.
Published: May 2015

Active neurons release neuroligin-3, which stimulates glioma proliferation.
Viral sensors get more involved
Authors: Foley John F.
Published: May 2015

The pattern recognition receptors RIG-I and MDA5 displace viral proteins that protect viral RNA in infected cells.
In Vitro
Activity of Dalbavancin against Drug-Resistant Staphylococcus aureus Isolates from a Global Surveillance Program
Authors: McCurdy Sandra P. , Jones Ronald N. , Mendes Rodrigo E. , Puttagunta Sailaja , Dunne Michael W.
Published: May 2015

In over a decade (2002 to 2012) of
Staphylococcus aureus
surveillance testing on 62,195 isolates, dalbavancin was demonstrated to be active against isolates that were either susceptible or nonsusceptible to daptomycin, linezolid, or tigecycline. Nearly all (99.8%) multidrug-resistant methicillin-resistant
S. aureus
isolates were inhibited by dalbavancin at ≤0.12 μg/ml (MIC
50/90
, 0.06/0.06 μg/ml), the current U.S. Food and Drug Administration (U.S. FDA) breakpoint. Overall, only 0.35% of the monitored
S. aureus
isolates had a dalbavancin MIC of either 0.25 or 0.5 μg/ml (i.e., were nonsusceptible).
Transfer of CMY-2 Cephalosporinase from Escherichia coli to Virulent Klebsiella pneumoniae Causing a Recurrent Liver Abscess
Authors: Lin Yi-Tsung , Pan Yi-Jiun , Lin Tzu-Lung , Fung Chang-Phone , Wang Jin-Town
Published: May 2015

A CMY-2-producing capsular type K2
Klebsiella pneumoniae
strain (TVGHKP93) with multidrug resistance was isolated from a recurrent liver abscess in a patient who also carried a CMY-2-producing
Escherichia coli
strain (TVGHEC01) in the stool. TVGHKP93 retained its high virulence compared with that of the isogenic strain (TVGHKP60) with wild-type resistance from the first liver abscess. Our conjugation experiment showed the successful transfer of the
bla
CMY-2
-carrying plasmid from TVGHEC01 into TVGHKP60. The transconjugant showed both high virulence and the multidrug-resistant phenotype, as did TVGHKP93.
Intensity and Mechanisms of Fluoroquinolone Resistance within the
H
30 and
H
30Rx Subclones of Escherichia coli Sequence Type 131 Compared with Other Fluoroquinolone-Resistant E. coli
Authors: Johnson James R. , Johnston Brian , Kuskowski Michael A. , Sokurenko Evgeni V. , Tchesnokova Veronika
Published: May 2015

The recent expansion of the
H
30 subclone of
Escherichia coli
sequence type 131 (ST131) and its CTX-M-15-associated
H
30Rx subset remains unexplained. Although ST131
H
30 typically exhibits fluoroquinolone resistance, so do multiple other
E. coli
lineages that have not expanded similarly. To determine whether
H
30 isolates have more intense fluoroquinolone resistance than other fluoroquinolone-resistant
E. coli
isolates and to identify possible mechanisms, we determined the MICs for four fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin, and norfloxacin) among 89 well-characterized, genetically diverse fluoroquinolone-resistant
E. coli
isolates (48 non-
H
30 and 41
H
30 [23
H
30Rx and 18
H
30 non-Rx]). We compared the MICs with the
H
30 and
H
30Rx status, the presence/number of nonsynonymous mutations in
gyrA
,
parC
, and
parE
, the presence of
aac
(
6
′)-
1b-cr
(an aminoglycoside/fluoroquinolone agent-modifying enzyme), and the efflux pump activity (measured as organic solvent tolerance [OST]). Among 1,518 recent
E. coli
clinical isolates, ST131
H
30 predominated clonally, both overall and among the fluoroquinolone-resistant isolates. Among the 89 study isolates, compared with non-
H
30 isolates,
H
30 isolates exhibited categorically higher MICs for all four fluoroquinolone agents, higher absolute ciprofloxacin and norfloxacin MICs, more nonsynonymous mutations in
gyrA
,
parC
, and
parE
(specifically
gyrA
D87N,
parC
E84V, and
parE
I529L), and a numerically higher prevalence of (
H
30Rx-associated)
aac
(
6
′)-
1b-cr
but lower OST scores. All putative resistance mechanisms were significantly associated with the MICs [for
aac
(
6
′)-
1b-cr
: ciprofloxacin and norfloxacin only].
parC
D87N corresponded with ST131
H
30 and
parE
I529L with ST131 generally. Thus, more intense fluoroquinolone resistance may provide ST131
H
30, especially
H
30Rx [if
aac
(
6
′)-
1b-cr
positive], with subtle fitness advantages over other fluoroquinolone-resistant
E. coli
strains. This urges both parsimonious fluoroquinolone use and a search for other fitness-enhancing traits within ST131
H
30.
In Vitro
Activity of Ceftolozane Alone and in Combination with Tazobactam against Extended-Spectrum-β-Lactamase-Harboring Enterobacteriaceae
Authors: Melchers Maria J. B. , van Mil Anita C. H. A. M. , Mouton Johan W.
Published: May 2015

Ceftolozane, formally CXA-101, is a new antipseudomonal cephalosporin that is also active
in vitro
against
Enterobacteriaceae
but is vulnerable to extended-spectrum β-lactamases (ESBLs). The addition of tazobactam is intended to broaden coverage to most ESBL-producing
Escherichia coli
and
Klebsiella pneumonia
as well as other
Enterobacteriaceae
. The
in vitro
activities of ceftolozane-tazobactam combinations against 67 clinically and molecularly characterized ESBL-producing isolates were examined by checkerboard MIC testing to evaluate their potential clinical feasibility and to assess the optimal tazobactam concentrations to be used in MIC determinations of ceftolozane. Isolates included those from
E. coli
(
n
= 32),
K. pneumoniae
(
n
= 19),
Enterobacter cloacae
(
n
= 15), and
Citrobacter freundii
(
n
= 1). Checkerboard experiments were performed to study interactions over the range of 0.008 to 64 mg/liter ceftolozane and 0.063 to 32 mg/liter tazobactam using 2-fold-dilution series. The MIC
50
and MIC
90
of ceftolozane alone for all isolates were 16 and ≥64 mg/liter, respectively. Increasing concentrations of tazobactam resulted in decreasing MICs of ceftolozane. The 50th and 90th percentile concentrations of tazobactam required to reduce the MIC of ceftolozane to 8 mg/liter for all organisms in this ESBL collection were 0.5 and 4 mg/liter, respectively. For
E. coli
,
K. pneumoniae
, and
E. cloacae
, these values were 0.5 and 2, 1 and 16, and 0.5 and 4 mg/liter, respectively. When combined with a fixed amount of 4 mg/liter tazobactam (current CLSI concentration used for susceptibility testing), 90% of the isolates would have an MIC of ≤4 mg/liter. The combination ceftolozane-tazobactam is a promising alternative option for treating infections due to ESBL-harboring isolates.
In Vitro
Antimicrobial Susceptibility Patterns of Blastocystis
Authors: Roberts Tamalee , Bush Stephen , Ellis John , Harkness John , Stark Damien
Published: May 2015

Blastocystis
is the most common human enteric protist with controversial clinical significance. Metronidazole is considered a first-line treatment for
Blastocystis
infection; however, there has been increasing evidence for the lack of efficacy of this treatment. Treatment failure has been reported in several clinical cases, and recent
in vitro
studies have suggested the occurrence of metronidazole-resistant strains. In this study, we tested 12
Blastocystis
isolates from 4 common
Blastocystis
subtypes (ST1, ST3, ST4, and ST8) against 12 commonly used antimicrobials (metronidazole, paromomycin, ornidazole, albendazole, ivermectin, trimethoprim-sulfamethoxazole [TMP-SMX], furazolidone, nitazoxanide, secnidazole, fluconazole, nystatin, and itraconazole) at 10 different concentrations
in vitro
. It was found that each subtype showed little sensitivity to the commonly used metronidazole, paromomycin, and triple therapy (furazolidone, nitazoxanide, and secnidazole). This study highlights the efficacy of other potential drug treatments, including trimethoprim-sulfamethoxazole and ivermectin, and suggests that current treatment regimens be revised.
Bactericidal Effects and Mechanism of Action of Olanexidine Gluconate, a New Antiseptic
Authors: Hagi Akifumi , Iwata Koushi , Nii Takuya , Nakata Hikaru , Tsubotani Yoshie , Inoue Yasuhide
Published: May 2015

Olanexidine gluconate [1-(3,4-dichlorobenzyl)-5-octylbiguanide gluconate] (development code OPB-2045G) is a new monobiguanide compound with bactericidal activity. In this study, we assessed its spectrum of bactericidal activity and mechanism of action. The minimal bactericidal concentrations of the compound for 30-, 60-, and 180-s exposures were determined with the microdilution method using a neutralizer against 320 bacterial strains from culture collections and clinical isolates. Based on the results, the estimated bactericidal olanexidine concentrations with 180-s exposures were 869 μg/ml for Gram-positive cocci (155 strains), 109 μg/ml for Gram-positive bacilli (29 strains), and 434 μg/ml for Gram-negative bacteria (136 strains). Olanexidine was active against a wide range of bacteria, especially Gram-positive cocci, including methicillin-resistant
Staphylococcus aureus
and vancomycin-resistant enterococci, and had a spectrum of bactericidal activity comparable to that of commercial antiseptics, such as chlorhexidine and povidone-iodine.
In vitro
experiments exploring its mechanism of action indicated that olanexidine (i) interacts with the bacterial surface molecules, such as lipopolysaccharide and lipoteichoic acid, (ii) disrupts the cell membranes of liposomes, which are artificial bacterial membrane models, (iii) enhances the membrane permeability of
Escherichia coli
, (iv) disrupts the membrane integrity of
S. aureus
, and (v) denatures proteins at relatively high concentrations (≥160 μg/ml). These results indicate that olanexidine probably binds to the cell membrane, disrupts membrane integrity, and its bacteriostatic and bactericidal effects are caused by irreversible leakage of intracellular components. At relatively high concentrations, olanexidine aggregates cells by denaturing proteins. This mechanism differs slightly from that of a similar biguanide compound, chlorhexidine.
First Staphylococcal Cassette Chromosome
mec
Containing a
mecB
-Carrying Gene Complex Independent of Transposon Tn
6045
in a Macrococcus caseolyticus Isolate from a Canine Infection
Authors: Gómez-Sanz Elena , Schwendener Sybille , Thomann Andreas , Gobeli Brawand Stefanie , Perreten Vincent
Published: May 2015

A methicillin-resistant
mecB
-positive
Macrococcus caseolyticus
(strain KM45013) was isolated from the nares of a dog with rhinitis. It contained a novel 39-kb transposon-defective complete
mecB
-carrying staphylococcal cassette chromosome
mec
element (SCC
mec
KM45013
). SCC
mec
KM45013
contained 49 coding sequences (CDSs), was integrated at the 3′ end of the chromosomal
orfX
gene, and was delimited at both ends by imperfect direct repeats functioning as integration site sequences (ISSs). SCC
mec
KM45013
presented two discontinuous regions of homology (SCC
mec
coverage of 35%) to the chromosomal and transposon Tn
6045
-associated SCC
mec
-like element of
M. caseolyticus
JCSC7096: (i) the
mec
gene complex (98.8% identity) and (ii) the
ccr
-carrying segment (91.8% identity). The
mec
gene complex, located at the right junction of the cassette, also carried the β-lactamase gene
blaZm
(
mecRm-mecIm-mecB-blaZm
). SCC
mec
KM45013
contained two cassette chromosome recombinase genes,
ccrAm2
and
ccrBm2
, which shared 94.3% and 96.6% DNA identity with those of the SCC
mec
-like element of JCSC7096 but shared less than 52% DNA identity with the staphylococcal
ccrAB
and
ccrC
genes. Three distinct extrachromosomal circularized elements (the entire SCC
mec
KM45013
, ΨSCC
mec
KM45013
lacking the
ccr
genes, and SCC
KM45013
lacking
mecB
) flanked by one ISS copy, as well as the chromosomal regions remaining after excision, were detected. An unconventional circularized structure carrying the
mecB
gene complex was associated with two extensive direct repeat regions, which enclosed two open reading frames (ORFs) (ORF46 and ORF51) flanking the chromosomal
mecB
-carrying gene complex. This study revealed
M. caseolyticus
as a potential disease-associated bacterium in dogs and also unveiled an SCC
mec
element carrying
mecB
not associated with Tn
6045
in the genus
Macrococcus
.
Causes and Implications of the Disappearance of Rifampin Resistance in a Rat Model of Methicillin-Resistant Staphylococcus aureus Foreign Body Osteomyelitis
Authors: Brinkman Cassandra L. , Tyner Harmony L. , Schmidt-Malan Suzannah M. , Mandrekar Jayawant N. , Patel Robin
Published: May 2015

Orthopedic foreign body-associated infections are often treated with rifampin-based combination antimicrobial therapy. We previously observed that rifampin-resistant and methicillin-resistant
Staphylococcus aureus
(MRSA) isolates were present 2 days after cessation of rifampin therapy in experimental foreign body osteomyelitis. Unexpectedly, only rifampin-susceptible isolates were detected 14 days after the completion of treatment. We studied two rifampin-resistant isolates recovered 2 days after treatment and one rifampin-susceptible isolate recovered 14 days after treatment. Growing these isolates alone
in vitro
or
in vivo
demonstrated no fitness defects; however, in mixed culture, rifampin-susceptible bacteria outcompeted rifampin-resistant bacteria.
In vivo
, two courses of rifampin treatment (25 mg/kg of body weight every 12 h for 21 days) yielded a greater decrease in bacterial quantity in the bones of treated animals 14 days following treatment than that in animals receiving a single course of treatment (
P
= 0.0398). In infections established with equal numbers of rifampin-resistant and rifampin-susceptible bacteria, one course of rifampin treatment did not affect bacterial quantities. Rifampin-resistant and rifampin-susceptible isolates were recovered both 2 days and 14 days following treatment completion; however, the proportion of animals with rifampin-resistant isolates was lower at 14 days than that at 2 days following treatment completion (
P
= 0.024). In untreated animals infected with equal numbers of rifampin-resistant and rifampin-susceptible bacteria for 4 weeks, rifampin-susceptible isolates were exclusively recovered, indicating the outcompetition of rifampin-resistant by rifampin-susceptible isolates. The data presented imply that although there is no apparent fitness defect in rifampin-resistant bacteria when grown alone, they are outcompeted by rifampin-susceptible bacteria when the two are present together. The findings also suggest that selected rifampin resistance may not persist in initially rifampin-susceptible infections following the discontinuation of rifampin.
A Derivative of the Thiopeptide GE2270A Highly Selective against Propionibacterium acnes
Authors: Fabbretti Attilio , He Cheng-Guang , Gaspari Eleonora , Maffioli Sonia , Brandi Letizia , Spurio Roberto , Sosio Margherita , Jabes Daniela , Donadio Stefano
Published: May 2015

A chemical derivative of the thiopeptide GE2270A, designated NAI003, was found to possess a substantially reduced antibacterial spectrum in comparison to the parent compound, being active against just a few Gram-positive bacteria. In particular, NAI003 retained low MICs against all tested isolates of
Propionibacterium acnes
and, to a lesser extent, against
Enterococcus faecalis
. Furthermore, NAI003 showed a time- and dose-dependent killing of both a clindamycin-resistant and a clindamycin-sensitive
P. acnes
isolate. Gel shift experiments indicated that, like the parent compound, NAI003 retained the ability to bind to elongation factors Tu (EF-Tus) derived from
Escherichia coli
,
E. faecalis
, or
P. acnes
, albeit with reduced efficiency. In contrast, EF-Tus derived from the NAI003-insensitive
Staphylococcus aureus
or
Streptococcus pyogenes
did not bind this compound. These results were confirmed by
in vitro
studies using a hybrid translation system, which indicated that NAI003 can inhibit most efficiently protein synthesis driven by the
P. acnes
EF-Tu.
P. acnes
mutants resistant to NAI003 were isolated by direct plating. With one exception, all analyzed strains carried mutations in the
tuf
gene, encoding EF-Tu. Because of its selective effect on
P. acnes
in comparison to resident skin flora, NAI003 represents a promising candidate for the topical treatment of acne, which has already completed a phase 1 clinical study.
Identifying Francisella tularensis Genes Required for Growth in Host Cells
Authors: Brunton J. , Steele S. , Miller C. , Lovullo E. , Taft-Benz S. , Kawula T.
Published: May 2015

Francisella tularensis
is a highly virulent Gram-negative intracellular pathogen capable of infecting a vast diversity of hosts, ranging from amoebae to humans. A hallmark of
F. tularensis
virulence is its ability to quickly grow to high densities within a diverse set of host cells, including, but not limited to, macrophages and epithelial cells. We developed a luminescence reporter system to facilitate a large-scale transposon mutagenesis screen to identify genes required for growth in macrophage and epithelial cell lines. We screened 7,454 individual mutants, 269 of which exhibited reduced intracellular growth. Transposon insertions in the 269 growth-defective strains mapped to 68 different genes.
FTT_0924
, a gene of unknown function but highly conserved among
Francisella
species, was identified in this screen to be defective for intracellular growth within both macrophage and epithelial cell lines.
FTT_0924
was required for full Schu S4 virulence in a murine pulmonary infection model. The Δ
FTT_0924
mutant bacterial membrane is permeable when replicating in hypotonic solution and within macrophages, resulting in strongly reduced viability. The permeability and reduced viability were rescued when the mutant was grown in a hypertonic solution, indicating that
FTT_0924
is required for resisting osmotic stress. The Δ
FTT_0924
mutant was also significantly more sensitive to β-lactam antibiotics than Schu S4. Taken together, the data strongly suggest that
FTT_0924
is required for maintaining peptidoglycan integrity and virulence.
Colonization of Epidermal Tissue by Staphylococcus aureus Produces Localized Hypoxia and Stimulates Secretion of Antioxidant and Caspase-14 Proteins
Authors: Lone Abdul G. , Atci Erhan , Renslow Ryan , Beyenal Haluk , Noh Susan , Fransson Boel , Abu-Lail Nehal , Park Jeong-Jin , Gang David R. , Call Douglas R.
Published: May 2015

A partial-thickness epidermal explant model was colonized with green fluorescent protein (GFP)-expressing
Staphylococcus aureus
, and the pattern of
S. aureus
biofilm growth was characterized using electron and confocal laser scanning microscopy. The oxygen concentration in explants was quantified using microelectrodes. The relative effective diffusivity and porosity of the epidermis were determined using magnetic resonance imaging, while hydrogen peroxide (H
2
O
2
) concentration in explant media was measured by using microelectrodes. Secreted proteins were identified and quantified using elevated-energy mass spectrometry (MS
E
).
S. aureus
biofilm grows predominantly in lipid-rich areas around hair follicles and associated skin folds. Dissolved oxygen was selectively depleted (2- to 3-fold) in these locations, but the relative effective diffusivity and porosity did not change between colonized and control epidermis. Histological analysis revealed keratinocyte damage across all the layers of colonized epidermis after 4 days of culture. The colonized explants released significantly (
P
< 0.01) more antioxidant proteins of both epidermal and
S. aureus
origin, consistent with elevated H
2
O
2
concentrations found in the media from the colonized explants (
P
< 0.001). Caspase-14 was also elevated significantly in the media from the colonized explants. While H
2
O
2
induces primary keratinocyte differentiation, caspase-14 is required for terminal keratinocyte differentiation and desquamation. These results are consistent with a localized biological impact from
S. aureus
in response to colonization of the skin surface.
Pathogenic Leptospira interrogans Exoproteins Are Primarily Involved in Heterotrophic Processes
Authors: Eshghi Azad , Pappalardo Elisa , Hester Svenja , Thomas Benjamin , Pretre Gabriela , Picardeau Mathieu
Published: May 2015

Leptospirosis is a life-threatening and emerging zoonotic disease with a worldwide annual occurrence of more than 1 million cases. Leptospirosis is caused by spirochetes belonging to the genusLeptospira. The mechanisms of disease manifestation in the host remain elusive, and the roles of leptospiral exoproteins in these processes have yet to be determined. Our aim in this study was to assess the composition and quantity of exoproteins of pathogenicLeptospira interrogansand to construe how these proteins contribute to disease pathogenesis. Label-free quantitative mass spectrometry of proteins obtained fromLeptospiraspirochetes culturedin vitrounder conditions mimicking infection identified 325 exoproteins. The majority of these proteins are conserved in the nonpathogenic speciesLeptospira biflexa, and proteins involved in metabolism and energy-generating functions were overrepresented and displayed the highest relative abundance in culture supernatants. Conversely, proteins of unknown function, which represent the majority of pathogen-specific proteins (presumably involved in virulence mechanisms), were underrepresented. Characterization of variousL. interrogansexoprotein mutants in the animal infection model revealed host mortality rates similar to those of hosts infected with wild-typeL. interrogans. Collectively, these results indicate that pathogenicLeptospiraexoproteins primarily function in heterotrophic processes (the processes by which organisms utilize organic substances as nutrient sources) to maintain the saprophytic lifestyle rather than the virulence of the bacteria. The underrepresentation of proteins homologous to known virulence factors, such as toxins and effectors in the exoproteome, also suggests that disease manifesting fromLeptospirainfection is likely caused by a combination of the primary and potentially moonlight functioning of exoproteins.
Tim-3 Induces Th2-Biased Immunity and Alternative Macrophage Activation during Schistosoma japonicum Infection
Authors: Hou Nan , Piao Xianyu , Liu Shuai , Wu Chuang , Chen Qijun
Published: May 2015

T cell immunoglobulin- and mucin-domain-containing molecule 3 (Tim-3) has been regarded as an important regulatory factor in both adaptive and innate immunity. Recently, Tim-3 was reported to be involved in Th2-biased immune responses in mice infected withSchistosoma japonicum, but the exact mechanism behind the involvement of Tim-3 remains unknown. The present study aims to understand the role of Tim-3 in the immune response againstS. japonicuminfection. Tim-3 expression was determined by flow cytometry, and increased Tim-3 expression was observed on CD4+and CD8+T cells, NK1.1+cells, and CD11b+cells from the livers ofS. japonicum-infected mice. However, the increased level of Tim-3 was lower in the spleen than in the liver, and no increase in Tim-3 expression was observed on splenic CD8+T cells or CD11b+cells. The schistosome-induced upregulation of Tim-3 on natural killer (NK) cells was accompanied by reduced NK cell numbersin vitroandin vivo. Tim-3 antibody blockade led to upregulation of inducible nitric oxide synthase and interleukin-12 (IL-12) mRNA in CD11b+cells cocultured with soluble egg antigen and downregulation of Arg1 and IL-10, which are markers of M2 macrophages. In summary, we observed schistosome-induced expression of Tim-3 on critical immune cell populations, which may be involved in the Th2-biased immune response and alternative activation of macrophages during infection.
Immunoprofiling of the Tryptophan-Rich Antigen Family in Plasmodium vivax
Authors: Wang Bo , Lu Feng , Cheng Yang , Chen Jun-Hu , Jeon Hye-Yoon , Ha Kwon-Soo , Cao Jun , Nyunt Myat Htut , Han Jin-Hee , Lee Seong-Kyun , Kyaw Myat Phone , Sattabongkot Jetsumon , Takashima Eizo , Tsuboi Takafumi , Han Eun-Taek
Published: May 2015

Tryptophan-rich antigens (TRAgs) are an antigen family that has been identified in human and rodent malaria parasites. TRAgs have been proposed as candidate antigens for potential vaccines. ThePlasmodium vivaxTRAg (PvTRAg) family includes 36 members. Each PvTRAg contains a tryptophan-rich (TR) domain in the C-terminal region. In this study, we recombinantly expressed all 36 PvTRAgs using a cell-free expression system, and, for the first time, profiled the IgG antibody responses against all PvTRAgs in the sera from 96 vivax malaria patients and 40 healthy individuals using protein microarray technology. The mean seropositive rate for all PvTRAgs was 60.3%. Among them, nine PvTRAgs were newly identified in this study and showed a seropositive rate of >50%. Five of them, PvTRAg_13, PvTRAg_15, PvTRAg_16, PvTRAg_26, and PvTRAg_29, produced higher levels of IgG antibody, even in low-endemicity countries. In addition, the results of an immunofluorescence analysis suggest that PvTRAgs are, at least in part, associated with caveola-vesicle complexes, a unique structure ofP. vivax-infected erythrocytes. The mechanism of formation and the function of these abundant membrane structures are not known. Further investigation aimed at determining the functions of these proteins would lead to a better understanding of the blood-stage biology ofP. vivax.
The Protein Interactome of Mycobacteriophage Giles Predicts Functions for Unknown Proteins
Authors: Mehla Jitender , Dedrick Rebekah M. , Caufield J. Harry , Siefring Rachel , Mair Megan , Johnson Allison , Hatfull Graham F. , Uetz Peter
Published: May 2015

Mycobacteriophages are viruses that infect mycobacterial hosts and are prevalent in the environment. Nearly 700 mycobacteriophage genomes have been completely sequenced, revealing considerable diversity and genetic novelty. Here, we have determined the protein complement of mycobacteriophage Giles by mass spectrometry and mapped its genome-wide protein interactome to help elucidate the roles of its 77 predicted proteins, 50% of which have no known function. About 22,000 individual yeast two-hybrid (Y2H) tests with four different Y2H vectors, followed by filtering and retest screens, resulted in 324 reproducible protein-protein interactions, including 171 (136 nonredundant) high-confidence interactions. The complete set of high-confidence interactions among Giles proteins reveals new mechanistic details and predicts functions for unknown proteins. The Giles interactome is the first for any mycobacteriophage and one of just five known phage interactomes so far. Our results will help in understanding mycobacteriophage biology and aid in development of new genetic and therapeutic tools to understand
Mycobacterium tuberculosis
.

IMPORTANCE
Mycobacterium tuberculosis
causes over 9 million new cases of tuberculosis each year. Mycobacteriophages, viruses of mycobacterial hosts, hold considerable potential to understand phage diversity, evolution, and mycobacterial biology, aiding in the development of therapeutic tools to control mycobacterial infections. The mycobacteriophage Giles protein-protein interaction network allows us to predict functions for unknown proteins and shed light on major biological processes in phage biology. For example, Giles gp76, a protein of unknown function, is found to associate with phage packaging and maturation. The functions of mycobacteriophage-derived proteins may suggest novel therapeutic approaches for tuberculosis. Our ORFeome clone set of Giles proteins and the interactome data will be useful resources for phage interactomics.
The Effectiveness of Acupuncture versus Clonazepam in Patients with Burning Mouth Syndrome
Authors: Jurisic Kvesic A , Zavoreo I , Basic Kes V , Vucicevic Boras V , Ciliga D , Gabric D , Vrdoljak D V
Published: May 2015

Objective

Burning mouth syndrome (BMS) is a chronic oral condition, characterised by burning symptoms, which mainly affects perimenopausal and postmenopausal women. Neuropathy might be the underlying cause of the condition. There are still insufficient data regarding successful therapy. The aim of this study was to compare the effectiveness of acupuncture and clonazepam.

Methods

Forty-two patients with BMS (38 women, 4 men) aged 66.7±12.0 years were randomly divided into two groups. Acupuncture was performed on 20 participants over 4 weeks, 3 times per week, on points ST8, GB2, TE21, SI19, SI18 and LI4 bilaterally as well as GV20 in the midline, each session lasting half an hour. Twenty-two patients took clonazepam once a day (0.5 mg in the morning) for 2 weeks and, after 2 weeks, two tablets (0.5 mg in the morning and in the evening) were taken for the next 2 weeks. Prior to and 1 month after either therapy, participants completed questionnaires: visual analogue scale, Beck Depression Inventory, Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale, 36-item Short Form Health Survey (SF-36) and Montreal Cognitive Assessment (MoCA).

Results

There were significant improvements in the scores of all outcome measures after treatment with both acupuncture and clonazepam, except for MoCA. There were no significant differences between the two therapeutic regimens regarding the scores of the performed tests.

Conclusions

Acupuncture and clonazepam are similarly effective for patients with BMS.
Contribution of recurrent admissions in children and young people to emergency hospital admissions: retrospective cohort analysis of hospital episode statistics
Authors: Wijlaars Linda PMM , Hardelid Pia , Woodman Jenny , Allister Janice , Cheung Ronny , Gilbert Ruth
Published: May 2015

Objective

To examine the contribution of recurrent admissions to the high rate of emergency admissions among children and young people (CYP) in England, and to what extent readmissions are accounted for by patients with chronic conditions.

Design

All hospital admissions to the National Health Service (NHS) in England using hospital episode statistics (HES) from 2009 to 2011 for CYP aged 0–24 years. We followed CYP for 2 years from discharge of their first emergency admission in 2009. We determined the number of subsequent emergency admissions, time to next admission, length of stay and the proportion of injury and chronic condition admissions measured by diagnostic codes in all following admissions.

Results

869 895 children had an index emergency admission in 2009, resulting in a further 939 710 admissions (of which 600 322, or 64%, were emergency admissions) over the next 2 years. After discharge from the index admission, 32% of 274,986 (32%) children were readmitted within 2 years, 26% of these readmissions occurring within 30 days of discharge. Recurrent emergency admission accounted for 41% of all emergency admissions in the 2-year cohort and 66% of inpatient days. 41% of index admissions, but 76% of the recurrent emergency admissions, were in children with a chronic condition.

Conclusions

Recurrent admissions contribute substantially to total emergency admissions. They often occur soon after discharge, and disproportionately affect CYP with chronic conditions. Policies aiming to discourage readmissions should consider whether they could undermine necessary inpatient care for children with chronic conditions.