bluuebunny/crossref_metadata_2025 huggingface dataset:
Canine progenitor epidermal keratinocytes express various inflammatory markers, including interleukin‐8 and CD40, which are affected by certain antibiotics
Authors: White Amelia G. , Wolsic Cassandra L. , Campbell Karen L. , Lavergne Sidonie N.
Published: August 2014

Background

Bacterial skin infections are common in dogs and humans. Keratinocytes have phenotypic features of nonprofessional antigen‐presenting cells and express various cytokines. However, little is known about the effects of antibiotics on inflammatory markers in canine keratinocytes.

Hypothesis/Objectives

To investigate inflammatory markers in canine progenitor epidermal keratinocytes (CPEKs) and to determine the effects of selected antibiotics on these markers.

Methods

The CPEKs were exposed for 2–24 h to three concentrations of amoxicillin, cefalexin, sulfadimethoxine, sulfamethoxazole (or its nitroso metabolite), amikacin or enrofloxacin. Enzyme‐linked immunosorbent assay (ELISA) and immunocytochemistry were used to detect major histocompatibility complex (MHC) II. CD40 and CXCR1 [interleukin (IL)‐8 receptor] were detected using ELISA. Secreted cytokines/chemokines were quantified using a multiplex kit.

Results

No MHC II protein was detected. CD40 protein was found at 24 h, with levels being significantly increased by enrofloxacin. The CPEKs secreted no detectable monocyte chemotactic protein‐1; undetectable to low (picogram per millilitre range) concentrations of IL‐6, IL‐7, IL‐10, IL‐15, tumour necrosis factor‐α, interferon‐γ and granulocyte–macrophage colony‐stimulating factor; and high (nanogram per millilitre range) concentrations of IL‐8. Levels of IL‐8 increased over 24 h following cell proliferation. They were significantly increased by enrofloxacin after 8 h, and by cefalexin, sulfadimethoxine, sulfamethoxazole, its nitroso metabolite and enrofloxacin after 24 h. The CPEKs expressed CXCR1.

Conclusions and clinical importance

Canine progenitor epidermal keratinocytes express various inflammatory proteins, with expression profiles being affected by certain antibiotics. This supports previous work showing keratinocytes to be mediators of inflammation and demonstrates the potential pro‐inflammatory effects of certain antibiotics in the skin.
COMPARISON OF COMPUTED TOMOGRAPHIC AND PATHOLOGIC FINDINGS IN 17 DOGS WITH PRIMARY ADRENAL NEOPLASIA
Authors: Gregori Tommaso , Mantis Panagiotis , Benigni Livia , Priestnall Simon L. , Lamb Christopher R.
Published: August 2014

The CT appearance of canine adrenal masses has been reported, but associations between imaging features and pathologic features of these lesions have not been investigated in detail. The purpose of this study was to test associations between different types of adrenal neoplasia and their CT and pathologic features. A retrospective cross‐sectional study was performed and inclusion criteria were histologic diagnosis of primary adrenal neoplasia, contrast‐enhanced CT examination of the abdomen and surgical resection of the mass or necropsy examination. For all included dogs, CT images and histopathologic specimens were reviewed independently by two veterinary radiologists and a veterinary pathologist, respectively. Seventeen dogs met inclusion criteria. Diagnoses were adenocarcinoma in nine (53%) dogs, pheochromocytoma in five (29%) dogs, and adenoma in three (18%) dogs. Pheochromocytoma was associated with CT signs of vascular invasion (likelihood ratio = 4.8, 95% CI = 1.3–18.3,P= 0.03) and macroscopic vascular invasion (likelihood ratio = 9.6, 95% CI = 1.4–65.9,P= 0.02). There was excellent agreement between signs of vascular invasion in CT images and vascular invasion at surgery or necropsy (kappa = 0.86,P= 0.001). A peripheral contrast‐enhancing rim in delayed postcontrast CT images was associated with fibrous encapsulation of the tumor (kappa = 0.53,P= 0.05), and a heterogeneous pattern of contrast distribution in delayed postcontrast CT images was associated with adrenal hemorrhage or infarction on histological examination (kappa = 0.45,P= 0.05). Findings indicated that CT enabled assessment of adrenal neoplasia features that reflected their biological behavior and pathological findings, however overlapping characteristics between tumor types limited the potential for reliably distinguishing them based on CT alone.
MAGNETIC RESONANCE IMAGING CHARACTERISTICS OF EQUINE HEAD DISORDERS: 84 CASES (2000–2013)
Authors: Manso‐Díaz Gabriel , Dyson Sue J. , Dennis Ruth , García‐López José M. , Biggi Marianna , García‐Real M. Isabel , San Román Fidel , Taeymans Olivier
Published: August 2014

The equine head is an anatomically complex area, therefore advanced tomographic imaging techniques, such as computed tomography or magnetic resonance imaging (MRI), are often required for diagnosis and treatment planning. The purpose of this multicenter retrospective study was to describe MRI characteristics for a large sample of horses with head disorders. Horses imaged over a period of 13 years were recruited. Eighty‐four horses met the inclusion criteria, having neurological (n = 65), sinonasal (n = 14), and soft tissue (n = 5) disorders. Magnetic resonance imaging accurately depicted the anatomy and allowed identification of the primary lesion and associated changes. There were good correlations between MRI findings and intraoperative or postmortem results. Magnetic resonance imaging showed the exact localization of the lesions, their size, and relation to surrounding structures. However, in the neurological group, there were 45 horses with no MRI abnormalities, 29 of which had a history of recurrent seizures, related to cryptogenic epilepsy. Magnetic resonance imaging was otherwise a valuable diagnostic tool, and can be used for studying a broad range of head disorders using either low‐field or high‐field magnets.
Longitudinal Tire Dynamics Model for Transient Braking Analysis: ANCF-LuGre Tire Model
Authors: Yamashita Hiroki , Matsutani Yusuke , Sugiyama Hiroyuki
Published: August 2014

In this investigation, the flexible tire model based on the absolute nodal coordinate formulation (ANCF) is integrated with LuGre tire friction model for evaluation of the longitudinal tire dynamics under severe braking scenarios. The ANCF-LuGre tire model developed allows for considering the nonlinear coupling between the dynamic structural deformation of the tire and its transient tire force distribution in the contact patch using general multibody dynamics computer algorithms. To this end, the contact patch obtained by the ANCF elastic ring tire model is discretized into small strips and the state of friction at each strip is defined by the differential equation associated with the discretized LuGre friction parameters. The normal contact pressure distribution predicted by the ANCF elastic ring elements that are in contact with the road surface are mapped onto the LuGre strips in the contact patch to evaluate the tangential tire force distribution and then the tire forces evaluated at LuGre strips are fed back to the generalized tangential contact forces of the ANCF elastic ring tire model. By doing so, the structural deformation of the ANCF elastic ring tire model is dynamically coupled with the LuGre tire friction in the final form of the governing equations. Furthermore, the systematic and automated parameter identification procedure for the LuGre tire force model is developed. It is shown that use of the proposed procedure with the modified friction curve proposed for wet road conditions leads to accurate prediction of the LuGre model parameters for measured tire force characteristics under various loading and speed conditions. Several numerical examples are presented in order to demonstrate the use of the in-plane ANCF-LuGre tire model for the longitudinal transient dynamics of tires under severe braking scenarios.
Cooling Performance Evaluation of Synthetic Jet Based Thermal Solution Module
Authors: Jalilvand Ahmad , Mochizuki Masataka , Saito Yuji , Kawahara Yoji , Singh Randeep , Wuttijumnong Vijit
Published: August 2014

The convective thermal resistance which represents the heat removal from the heat sink surface of a heat pipe/heat sink module to mean coolant flow temperature is often a dominant contributor to the overall thermal resistance of a heat pipe/heat sink module or remote heat exchange (RHE). RHE is a thermal solution module composed of a heat spreader, thin flattened heat pipe with low profile heat sink which is widely used for the thermal management of compact portable electronic devices. Minimizing the convective thermal resistance at the heat sink of RHE as well as thickness reduction is often an important objective for the thermal designers. Recently, an alternate air mover system which operates based on piezoelectricity is developed. This device is called dual cooling jet (DCJ) in short which can be fabricated with very small thickness down to 1.0 mm. Thin DCJ as a synthetic jet generates air jet with more than 7 m/s air flow velocity which is promising for the increasing demands of thinner next generation portable electronic devices. DCJ is a promising device to dissipate the heat from the heat sink of a RHE. In this work, the performance of RHE is evaluated when heat is dissipated from its heat sink by DCJ. The results are compared with conventional rotary fan. The results show that more than 12 W of heat can be dissipated by DCJ which can easily compete with some commercialized rotary mini blowers while having much smaller thickness. Various configuration of heat sink–DCJ combinations as well as size and shape of both heat sink and DCJ are tested and based on thermal resistance data, cooling effectiveness of DCJ is studied.
Numerical Simulations of a Ground Source Heat Pump System With Pile Heat Exchangers
Authors: Oguma Masahito , Matsumoto Takeshi , Kakizaki Takao
Published: August 2014

Feasibility of a ground source heat pump (GSHP) system with pile heat exchangers for use in houses is evaluated through a numerical simulation. This GSHP system differs from ordinary borehole-type GSHP systems because short foundation piles installed at close intervals are used as heat exchangers. It is shown that the annual heat supply provided by this GSHP system is able to satisfy the demand of a house due to the air-source exchange at ground surface.
Simulation of an Industrial Tangentially Fired Boiler Firing Metallurgical Gases
Authors: Tang Guangwu , Wu Bin , Johnson Kurt , Kirk Albert , Zhou Chenn Q.
Published: August 2014

In industrial environments, boiler units are widely used to supply heat and electrical power. At an integrated steel mill, industrial boilers combust a variable mixture of metallurgical gases combined with additional fuels to generate high-pressure superheated steam. Most tangentially fired boilers have experienced water wall tube failures in the combustion zone, which are thought to be caused by some deficiency in the combustion process. The challenge faced in this present process is that there are very limited means to observe the boiler operation. In this study, a three-dimensional computational fluid dynamics (CFD) modeling and simulation of an industrial tangentially fired boiler firing metallurgical gases was conducted. Eddy dissipation combustion model was applied on this multiple fuel combustion process. Simulation results obtained from the developed CFD model were validated by industrial experiments. A quick comparison of the flame shape from the simulation to the actual flame in the boiler showed a good agreement. The flow field and temperature distribution inside the tangentially fired boiler were analyzed under the operation conditions, and a wall water tube overheating problem was observed and directly related to the flow characteristics.
Effect of Tube Geometry and Curvature on Film Condensation in the Presence of a Noncondensable Gas
Authors: Li Huijun , Peng Wenping , Liu Yingguang , Ma Chao
Published: August 2014

Based on the double boundary layer theory, a generalized mathematical model was developed to study the distributions of gas film, liquid film, and heat transfer coefficient along the tube surface with different geometries and curvatures for film condensation in the presence of a noncondensable gas. The results show that: (i) for tubes with the same geometry, gas film thickness, and liquid film thickness near the top of the tube decrease with the increasing of curvature and the heat transfer rate increases with it. (ii) For tubes with different geometries, one need to take into account all factors to compare their overall heat transfer rate including gas film thickness, liquid film thickness and the separating area. Besides, the mechanism of the drainage and separation of gas film and liquid film was analyzed in detail. One can make a conclusion that for free convection, gas film never separate since parameter A is always positive, whereas liquid film can separate if parameter B becomes negative. The separating angle of liquid film decreases with the increasing of curvature.
Assessment of Two-Phase Cooling of Power Electronics Using Roll-Bonded Condensers
Authors: Gradinger Thomas B. , Agostini Francesco
Published: August 2014

Two-phase thermosyphons with condensers from roll-bonded panels, short “roll-bond thermosiphons,” are attractive for power-electronics cooling. Using simulations, the performance of roll-bond thermosyphons and classical heat sinks is compared. The roll-bond thermosyphons are advantageous in terms of trade-off between thermal resistance, cooler volume or mass, and sound-power level. Under forced convection, where air-side heat-transfer coefficients are comparatively high, the classical heat sink suffers from low fin efficiency and limited heat spreading. By increasing the number of panels, the roll-bond thermosyphon enables low thermal resistances that cannot be practically reached with classical heat sinks. For free air convection, the roll-bond thermosyphon allows a significant reduction of thermal resistance and cooler mass.
The Biology Phenomenon Categorizer: A Human Computation Framework in Support of Biologically Inspired Design
Authors: Arlitt Ryan M. , Immel Sebastian R. , Berthelsdorf Friederich A. , Stone Robert B.
Published: August 2014

Locating relevant biological analogies is a challenge that lies at the heart of practicing biologically inspired design. Current computer-assisted biologically inspired design tools require human-in-the-loop synthesis of biology knowledge. Either a biology expert must synthesize information into a standard form, or a designer must interpret and assess biological strategies. These approaches limit knowledge breadth and tool usefulness, respectively. The work presented in this paper applies the technique of human computation, a historically successful approach for information retrieval problems where both breadth and accuracy are required, to address a similar problem in biologically inspired design. The broad goals of this work are to distribute the knowledge synthesis step to a large number of nonexpert humans, and to capture that synthesized knowledge in a format that can support analogical reasoning between designed systems and biological systems. To that end, this paper presents a novel human computation game and accompanying information model for collecting computable descriptions of biological strategies, an assessment of the quality of these descriptions gathered from experimental data, and a brief evaluation of the game's entertainment value. Two successive prototypes of the biology phenomenon categorizer (BioP-C); a cooperative, asymmetric, online game; were each deployed in a small engineering graduate class in order to collect assertions about the biological phenomenon of cell division. Through the act of playing, students formed assertions describing key concepts within textual passages. These assertions are assessed for their correctness, and these assessments are used to identify directly measurable correctness indicators. The results show that the number of hints in a game session is negatively correlated with assertion correctness. Further, BioP-C assertions are rated as significantly more correct than randomly generated assertions in both prototype tests, demonstrating the method's potential for gathering accurate information. Tests on these two different BioP-C prototypes produce average assertion correctness assessments of 3.19 and 2.98 on a five-point Likert scale. Filtering assertions on the optimal number of game session hints within each prototype test increases these mean values to 3.64 and 3.36. The median assertion correctness scores are similarly increased from 3.00 and 3.00 in both datasets to 4.08 and 3.50. Players of the game expressed that the fundamental anonymous interactions were enjoyable, but the difficulty of the game can harm the experience. These results indicate that a human computation approach has the potential to solve the problem of low information breadth currently faced by biologically inspired design databases.
Experimentally Verified Study of Regeneration-Induced Forced Response in Axial Turbines
Authors: Aschenbruck Jens , Seume Joerg R.
Published: August 2014

Geometrical variations occur in highly loaded turbine blades due to operation and regeneration. To determine the influence of such regeneration-induced variances of turbine blades on the aerodynamic excitation, a typical stagger angle variation of overhauled turbine blades is applied to stator vanes of an air turbine. This varied turbine stage is numerically and experimentally investigated. For the aerodynamic investigation of the vane wake, computational fluid dynamics (CFD) simulations are conducted. It is shown that the wake is changed due to the stagger angle variation. These results are confirmed by aerodynamic probe measurements in the air turbine. The vibration amplitude of the downstream rotor blades has been determined by a computational forced response analysis using a unidirectional fluid–structure interaction (FSI) approach and is experimentally verified here by tip-timing measurements. The results of the simulations and the measurements both show significantly higher amplitudes at certain operating points (OPs) due to the additional wake excitation. For typical regeneration-induced variations in stagger angle, the vibration amplitude is up to five times higher than in the reference case of uniform upstream stators. Based upon the present results, the influence of these variations and of the vane patterns on the vibration amplitude of the downstream rotor blade can and should be estimated in the regeneration process to minimize the dynamic stresses of the blades.
Preliminary evaluation of a two-interval, two-alternative infant behavioral testing procedure
Authors: Browning Jenna , Buss Emily , Leibold Lori J.
Published: August 2014

The purpose of this study was to evaluate the feasibility and efficiency of an observer-based, two-interval forced-choice infant psychophysical testing procedure. Ten of 11 infants (7–9 months of age) achieved a criterion of 80%-correct detection of a 50-dB sound pressure level noise band in a single testing session. Fewer trials were needed to reach criterion using the two-interval procedure than previously reported for the single-interval observer-based psychophysical procedure [Olsho, Koch, Halpin, and Carter (1987). Devel. Psychol. 23, 627–640]. These results provide preliminary evidence that the two-interval procedure is feasible and efficient while controlling for observer and listener response bias.
Outflanking RANK with a Designer Antagonist Cytokine
Authors: Ou-Yang Chih-Wen , Siegel Richard M.
Published: August 2014

A single-chain fusion protein of cytokine subunits with opposing affinities for their receptor acts as an effective receptor antagonist.
Characterization of a Novel AmpC β-Lactamase Produced by a Carbapenem-Resistant Cedecea davisae Clinical Isolate
Authors: Ammenouche Nacim , Dupont Hervé , Mammeri Hedi
Published: August 2014

A
Cedecea davisae
isolate, which was intermediate or resistant to third-generation cephalosporins and carbapenems, was recovered from a urine sample. Susceptibility testing, isoelectric focusing, and analysis of outer membrane proteins showed that AmpC β-lactamase expression combined with porin deficiency accounted for the carbapenem resistance. A cloning experiment followed by phenotypic and enzymatic characterization identified a novel class C enzyme that was phylogenetically and biochemically close to the chromosome-borne β-lactamases of the genera
Enterobacter
and
Citrobacter
.
Safety, Tolerability, and Efficacy of GSK1322322 in the Treatment of Acute Bacterial Skin and Skin Structure Infections
Authors: Corey Ralph , Naderer Odin J. , O'Riordan William D. , Dumont Etienne , Jones Lori S. , Kurtinecz Milena , Zhu John Z.
Published: August 2014

GSK1322322 represents a new class of antibiotics that targets an essential bacterial enzyme required for protein maturation, peptide deformylase. This multicenter, randomized, phase IIa study compared the safety, tolerability, and efficacy of GSK1322322 at 1,500 mg twice daily (b.i.d.) with that of linezolid at 600 mg b.i.d. in patients suspected of having Gram-positive acute bacterial skin and skin structure infections (ABSSSIs). The primary endpoint was assessment of the safety of GSK1322322, and a key secondary endpoint was the number of subjects with a ≥20% decrease in lesion area from the baseline at 48 and 72 h after treatment initiation. GSK1322322 administration was associated with mild-to-moderate drug-related adverse events, most commonly, nausea, vomiting, diarrhea, and headache. Adverse events (86% versus 74%) and withdrawals (28% versus 11%) were more frequent in the GSK1322322-treated group. Treatment with GSK1322322 and linezolid was associated with ≥20% decreases from the baseline in the lesion area in 73% (36/49) and 92% (24/26) of the patients, respectively, at the 48-h assessment and in 96% (44/46) and 100% (25/25) of the patients, respectively, at the 72-h assessment. Reductions in exudate/pus, pain, and skin infection scores were comparable between the GSK1322322 and linezolid treatments. The clinical success rates within the intent-to-treat population and the per-protocol population that completed this study were 67 and 91%, respectively, in the GSK1322322-treated group and 89 and 100%, respectively, in the linezolid-treated group. These results will be used to guide dose selection in future studies with GSK1322322 to optimize its tolerability and efficacy in patients with ABSSSIs. (This study has been registered at
ClinicalTrials.gov
under registration no. NCT01209078 and at
http://www.gsk-clinicalstudyregister.com
[PDF113414].)
Pharmacokinetics of Tedizolid in Subjects with Renal or Hepatic Impairment
Authors: Flanagan S. , Minassian S. L. , Morris D. , Ponnuraj R. , Marbury T. C. , Alcorn H. W. , Fang E. , Prokocimer P.
Published: August 2014

Two open-label, single-dose, parallel-group studies were conducted to characterize the pharmacokinetics of the novel antibacterial tedizolid and the safety of tedizolid phosphate, its prodrug, in renally or hepatically impaired subjects. Tedizolid pharmacokinetics in subjects with severe renal impairment without dialysis support was compared with that of matched control subjects with normal renal function. Effects of hemodialysis on tedizolid pharmacokinetics were determined in a separate cohort of subjects undergoing long-term hemodialysis. Effects of hepatic impairment on tedizolid pharmacokinetics were determined in subjects with moderate or severe hepatic impairment and compared with those of matched control subjects with normal hepatic function. Each participant received a single oral (hepatic impairment) or intravenous (renal impairment) dose of tedizolid phosphate at 200 mg; hemodialysis subjects received two doses (separated by 7 days), before and after dialysis, in a crossover fashion. The pharmacokinetics of tedizolid was similar in subjects with severe renal impairment and controls (∼8% lower area under the concentration-time curve [AUC], with a nearly identical peak concentration) and in subjects undergoing hemodialysis before and after tedizolid phosphate administration (∼9% lower AUC, with a 15% higher peak concentration); <10% of the dose was removed during 4 h of hemodialysis. Tedizolid pharmacokinetics was only minimally altered in subjects with moderate or severe hepatic impairment; the AUC was increased approximately 22% and 34%, respectively, compared with that of subjects in the control group. Tedizolid phosphate was generally well tolerated in all participants. These results suggest that tedizolid phosphate dose adjustments are not necessary in patients with any degree of renal or hepatic impairment. (This study has been registered at ClinicalTrials.gov under registration numbers NCT01452828 [renal study] and NCT01431833 [hepatic study].)
A First-in-Human Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple-Ascending Oral Dose Study of Novel Imidazolopiperazine KAF156 To Assess Its Safety, Tolerability, and Pharmacokinetics in Healthy Adult Volunteers
Authors: Leong F. Joel , Zhao Rong , Zeng Shuqi , Magnusson Baldur , Diagana Thierry T. , Pertel Peter
Published: August 2014

KAF156 belongs to a new class of antimalarial, the imidazolopiperazines, and is currently in clinical development for the treatment of uncomplicated malaria. This first-in-human, single- and multiple-ascending-dose study in 70 healthy male volunteers determined the maximum oral dose of KAF156 tolerated by healthy adults and derived pharmacokinetic data (including preliminary food effect) to enable dose calculations for malaria patients. KAF156 was studied in single-dose cohorts (10 to 1,200 mg, including one 400-mg food effect cohort (4 to 10 subjects/cohort), and in multiple-dose cohorts (60 to 600 mg once daily for 3 days; 8 subjects/cohort). The follow-up period was 6 to 14 days after the last dose. KAF156 was tolerated, with self-limited mild to moderate gastrointestinal and neurological adverse events. In treated subjects after single doses, headache (
n
= 4; 11.1%), diarrhea (
n
= 3; 8.3%), dizziness (
n
= 3; 8.3%), and abdominal pain (
n
= 2; 5.6%) were the most common adverse events. Headache (
n
= 4; 16.7%), nausea (
n
= 3; 12.5%), upper respiratory tract infection (
n
= 3; 12.5%), and dizziness (
n
= 2; 8.3%) were the most common adverse events following multiple doses. KAF156 time to maximum concentration (
T
max
) was between 1.0 and 6.0 h. Both the area under the concentration-time curve (AUC) and maximum concentration (
C
max
) increased more than dose-proportionally in both single- and multiple-ascending-dose cohorts (terminal half-life, 42.5 to 70.7 h). There was no significant accumulation over 3-day repeated administration. The extent of absorption was not significantly affected by food at a single dose of 400 mg, while mean
C
max
decreased from 778 ng/ml to 627 ng/ml and
T
max
was delayed from a median of 3.0 h under fasting conditions to 6.0 h under fed conditions. Renal elimination is a minor route.
Efficacy of a Ceftazidime-Avibactam Combination in a Murine Model of Septicemia Caused by Enterobacteriaceae Species Producing AmpC or Extended-Spectrum β-Lactamases
Authors: Levasseur Premavathy , Girard Anne-Marie , Lavallade Ludovic , Miossec Christine , Pace John , Coleman Kenneth
Published: August 2014

Avibactam is a novel non-β-lactam β-lactamase inhibitor that has been shown
in vitro
to inhibit class A, class C, and some class D β-lactamases. It is currently in phase 3 of clinical development in combination with ceftazidime. In this study, the efficacy of ceftazidime-avibactam was evaluated in a murine septicemia model against five ceftazidime-susceptible (MICs of 0.06 to 0.25 μg/ml) and 15 ceftazidime-resistant (MICs of 64 to >128 μg/ml) species of
Enterobacteriaceae
, bearing either TEM, SHV, CTX-M extended-spectrum, or AmpC β-lactamases. In the first part of the study, ceftazidime-avibactam was administered at ratios of 4:1 and 8:1 (wt/wt) to evaluate the optimal ratio for efficacy. Against ceftazidime-susceptible isolates of
Klebsiella pneumoniae
and
Escherichia coli
, ceftazidime and ceftazidime-avibactam demonstrated similar efficacies (50% effective doses [ED
50
] of <1.5 to 9 mg/kg of body weight), whereas against ceftazidime-resistant β-lactamase-producing strains (ceftazidime ED
50
of >90 mg/kg), the addition of avibactam restored efficacy to ceftazidime (ED
50
dropped to <5 to 65 mg/kg). In a subsequent study, eight isolates (two AmpC and six CTX-M producers) were studied in the septicemia model. Ceftazidime-avibactam was administered at a 4:1 (wt/wt) ratio, and the efficacy was compared to that of the 4:1 (wt/wt) ratio of either piperacillin-tazobactam or cefotaxime-avibactam. Against the eight isolates, ceftazidime-avibactam was the more effective combination, with ED
50
values ranging from 2 to 27 mg/kg compared to >90 mg/kg and 14 to >90 mg/kg for piperacillin-tazobactam and cefotaxime-avibactam, respectively. This study demonstrates that the potent
in vitro
activity observed with the ceftazidime-avibactam combination against ceftazidime-resistant
Enterobacteriaceae
species bearing class A and class C β-lactamases translated into good efficacy in the mouse septicemia model.
Comparison of
In Vivo
and
In Vitro
Pharmacodynamics of a Humanized Regimen of 600 Milligrams of Ceftaroline Fosamil Every 12 Hours against Staphylococcus aureus at Initial Inocula of 10
6
and 10
8
CFU per Milliliter
Authors: So Wonhee , Crandon Jared L. , Zhanel George G. , Nicolau David P.
Published: August 2014

In light of the
in vivo
/
in vitro
discordance among beta-lactams against Gram-negative pathogens, we compared the
in vivo
pharmacodynamics of humanized ceftaroline against 9
Staphylococcus aureus
strains (MICs of 0.13 to 1 mg/liter) from published
in vitro
studies using standard and high inocula in the murine thigh infection model. Consistent with the
in vitro
findings, mean reductions of ≥1 log
10
CFU were observed for ceftaroline against all strains using both standard and high inocula. These results suggest
in vivo
/
in vitro
concordance with no observed inoculum effect.
Role of PBPD1 in Stimulation of Listeria monocytogenes Biofilm Formation by Subminimal Inhibitory β-Lactam Concentrations
Authors: Nguyen Uyen T. , Harvey Hanjeong , Hogan Andrew J. , Afonso Alexandria C. F. , Wright Gerard D. , Burrows Lori L.
Published: August 2014

Disinfectant-tolerant
Listeria monocytogenes
biofilms can colonize surfaces that come into contact with food, leading to contamination and, potentially, food-borne illnesses. To better understand the process of
L. monocytogenes
biofilm formation and dispersal, we screened 1,120 off-patent FDA-approved drugs and identified several that modulate
Listeria
biofilm development. Among the hits were more than 30 β-lactam antibiotics, with effects ranging from inhibiting (≤50%) to stimulating (≥200%) biofilm formation compared to control. Most β-lactams also dispersed a substantial proportion of established biofilms. This phenotype did not necessarily involve killing, as >50% dispersal could be achieved with concentrations as low as 1/20 of the MIC of some cephalosporins. Penicillin-binding protein (PBP) profiling using a fluorescent penicillin analogue showed similar inhibition patterns for most β-lactams, except that biofilm-stimulatory drugs did not bind PBPD1, a low-molecular-weight
d
,
d
-carboxypeptidase. Compared to the wild type, a
pbpD1
mutant had an attenuated biofilm response to stimulatory β-lactams. The cephalosporin-responsive CesRK two-component regulatory system, whose regulon includes PBPs, was not required for the response. The requirement for PBPD1 activity for β-lactam stimulation of
L. monocytogenes
biofilms shows that the specific set of PBPs that are inactivated by a particular drug dictates whether a protective biofilm response is provoked.
Characterization of Wheat Germ Agglutinin Lectin-Reactive Glycosylated OmpA-Like Proteins Derived from Porphyromonas gingivalis
Authors: Murakami Yukitaka , Hasegawa Yoshiaki , Nagano Keiji , Yoshimura Fuminobu
Published: August 2014

Glycosylation is one of the common posttranslational modifications in eukaryotes. Recently, glycosylated proteins have also been identified in prokaryotes. A few glycosylated proteins, including gingipains, have been identified in
Porphyromonas gingivalis
, a major pathogen associated with chronic periodontitis. However, no other glycosylated proteins have been found. The present study identified glycoproteins in
P. gingivalis
cell lysates by lectin blotting. Whole-cell lysates reacted with concanavalin A (ConA),
Lens culinaris
agglutinin (LCA),
Phaseolus vulgaris
erythroagglutinin (PHA-E4), and wheat germ agglutinin (WGA), suggesting the presence of mannose-,
N
-acetylgalactosamine-, or
N
-acetylglucosamine (GlcNAc)-modified proteins. Next, glycoproteins were isolated by ConA-, LCA-, PHA-E4-, or WGA-conjugated lectin affinity chromatography although specific proteins were enriched only by the WGA column. Mass spectrometry analysis showed that an OmpA-like, heterotrimeric complex formed by Pgm6 and Pgm7 (Pgm6/7) was the major glycoprotein isolated from
P. gingivalis
. Deglycosylation experiments and Western blotting with a specific antibody indicated that Pgm6/7 was modified with
O
-GlcNAc. When whole-cell lysates from
P. gingivalis
mutant strains with deletions of Pgm6 and Pgm7 were applied to a WGA column, homotrimeric Pgm7, but not Pgm6, was isolated. Heterotrimeric Pgm6/7 had the strongest affinity for fibronectin of all the extracellular proteins tested, whereas homotrimeric Pgm7 showed reduced binding activity. These findings suggest that the heterotrimeric structure is important for the biological activity of glycosylated WGA-binding OmpA-like proteins in
P. gingivalis
.
Early Innate Immunity to Bacterial Infection in the Lung Is Regulated Systemically by the Commensal Microbiota via Nod-Like Receptor Ligands
Authors: Clarke Thomas B.
Published: August 2014

The commensal microbiota is a major regulator of the immune system. The majority of commensal bacteria inhabit the gastrointestinal tract and are known to regulate local mucosal defenses against intestinal pathogens. There is growing appreciation that the commensal microbiota also regulates immune responses at extraintestinal sites. Currently, however, it is unclear how this influences host defenses against bacterial infection outside the intestine. Microbiota depletion caused significant defects in the early innate response to lung infection by the major human pathogen
Klebsiella pneumoniae
. After microbiota depletion, early clearance of
K. pneumoniae
was impaired, and this could be rescued by administration of bacterial Nod-like receptor (NLR) ligands (the NOD1 ligand MurNAcTri
DAP
and NOD2 ligand muramyl dipeptide [MDP]) but not bacterial Toll-like receptor (TLR) ligands. Importantly, NLR ligands from the gastrointestinal, but not upper respiratory, tract rescued host defenses in the lung. Defects in early innate immunity were found to be due to reduced reactive oxygen species-mediated killing of bacteria by alveolar macrophages. These data show that bacterial signals from the intestine have a profound influence on establishing the levels of antibacterial defenses in distal tissues.
Lipopolysaccharides Belonging to Different Salmonella Serovars Are Differentially Capable of Activating Toll-Like Receptor 4
Authors: Chessa Daniela , Spiga Luisella , De Riu Nicola , Delaconi Paola , Mazzarello Vittorio , Ganau Giulia , Rubino Salvatore
Published: August 2014

Salmonella enterica
subsp.
enterica
serovar (serotype) Abortusovis is a member of the
Enterobacteriaceae
. This serotype is naturally restricted to ovine species and does not infect humans. Limited information is available about the immune response of sheep to
S
. Abortusovis.
S
. Abortusovis, like
Salmonella enterica
subsp.
enterica
serovar Typhi, causes a systemic infection in which, under natural conditions, animals are not able to raise a rapid immune response. Failure to induce the appropriate response allows pathogens to reach the placenta and results in an abortion. Lipopolysaccharides (LPSs) are pathogen-associated molecular patterns (PAMPs) that are specific to bacteria and are not synthesized by the host. Toll-like receptors (TLRs) are a family of receptors that specifically recognize PAMPs. As a first step, we were able to identify the presence of Toll-like receptor 4 (TLR4) on the ovine placenta by using an immunohistochemistry technique. To our knowledge, this is the first work describing the interaction between
S
. Abortusovis LPS and TLR4. Experiments using an embryonic cell line (HEK293) transfected with human and ovine TLR4s showed a reduction of interleukin 8 (IL-8) production by
S
. Abortusovis and
Salmonella enterica
subsp.
enterica
serovar Paratyphi upon LPS stimulation compared to
Salmonella enterica
subsp.
enterica
serovar Typhimurium. Identical results were observed using heat-killed bacteria instead of LPS. Based on data obtained with TLR4
in vitro
stimulation, we demonstrated that the serotype
S
. Abortusovis is able to successfully evade the immune system whereas
S
. Typhimurium and other serovars fail to do so.
Contributions of NanI Sialidase to Caco-2 Cell Adherence by Clostridium perfringens Type A and C Strains Causing Human Intestinal Disease
Authors: Li Jihong , McClane Bruce A.
Published: August 2014

Previous studies showed that
Clostridium perfringens
type D animal disease strain CN3718 uses NanI sialidase for adhering to enterocyte-like Caco-2 cells. The current study analyzed whether NanI is similarly important when type A and C human intestinal disease strains attach to Caco-2 cells. A PCR survey determined that the
nanI
gene was absent from typical type A food poisoning (FP) strains carrying a chromosomal enterotoxin (CPE) gene or the genetically related type C Darmbrand (Db) strains. However, the
nanI
gene was present in type A strains from healthy humans, type A strains causing CPE-associated antibiotic-associated diarrhea (AAD) or sporadic diarrhea (SD), and type C Pig-Bel strains. Consistent with NanI sialidase being the major
C. perfringens
sialidase when produced, FP and Db strains had little supernatant sialidase activity compared to other type A or C human intestinal strains. All type A and C human intestinal strains bound to Caco-2 cells, but NanI-producing strains had higher attachment levels. When produced, NanI can contribute to host cell attachment of human intestinal disease strains, since a
nanI
null mutant constructed in type A SD strain F4969 had lower Caco-2 cell adhesion than wild-type F4969 or a complemented strain. Further supporting a role for NanI in host cell attachment, sialidase inhibitors reduced F4969 adhesion to Caco-2 cells. Collectively, these results suggest that NanI may contribute to the intestinal attachment and colonization needed for the chronic diarrhea of CPE-associated AAD and SD, but this sialidase appears to be dispensable for the acute pathogenesis of type A FP or type C enteritis necroticans.
Relationship between Buckling of Acupuncture Needles and the Handle Type
Authors: Zhang Claire Shuiqing , Pannirselvan Muthu , Xue Charlie Changli , Xie Yi Min
Published: August 2014

Background

Most popular single-use acupuncture needles consist of a stainless steel shaft with a handle made of copper coil or plastic stick.

Objectives

To determine the strengths and weaknesses of these two handle types for needle buckling.

Methods

The buckling load for acupuncture needles with these two different handle types was determined using a digital scale, and the stiffness of stainless steel wires used in different types of acupuncture needles was measured using a Dynamic Mechanical Analysis machine.

Results

This study showed that an acupuncture needle with a copper coil handle was far more susceptible to buckling than a needle with a plastic stick handle. The average buckling force of acupuncture needles with plastic stick handles was 46.7% higher than that with copper coil handles for needles of 0.25 mm×30 mm, and 30.8% higher for needles of 0.25 mm×60 mm. Replacing a copper coil handle with a plastic stick handle could save about 100 tonnes of copper wires and 20 million metres of medical grade stainless steel wire a year worldwide.

Conclusions

The results from this study suggest that the common practice of using coiled copper for handles on acupuncture needles should be re-evaluated. Replacing a copper coil handle with a plastic stick handle would significantly reduce needle buckling and improve patient comfort and safety. This would also reduce the consumption of copper and medical grade stainless steel wire considerably.
The disappearing clip: an unusual complication in MRI biopsy
Authors: Bourke Anita Geraldine , Peter Prasant , Jose Chaitra Lesli
Published: August 2014

MRI-guided biopsies are being increasingly used for otherwise occult breast lesions. Clip migration has been reported however, to the best of our knowledge, there have been no documented cases of entire disappearance of a marker clip. Absence of the postbiopsy marker clip was noted when our patient returned for preoperative hook-wire localisation even though accurate clip placement had been confirmed on the post-MRI biopsy mammogram.
Fatal measles presenting as acute respiratory distress syndrome in an immunocompetent adult
Authors: Karanth Suman S , Marupudi Krishna Chaitanya , Gupta Anurag , Rau Nileshwar Radhakrishna
Published: August 2014

Fatal measles is known to occur among immunocompromised adults. We report a rare case of an immunocompetent non-pregnant young lady who suffered from fatal acute respiratory distress syndrome due to measles. Physicians must be vigilant to this deadly presentation of measles even in immunocompetent individuals. We emphasise the inadequacies of vaccination programmes in India reflected not only by the existing high measles-related childhood mortalities, but also an emerging rise in deaths among adults.
Obstructed ileostomy in the third trimester of pregnancy due to compression from the gravid uterus: diagnosis and management
Authors: Porter Hugh , Seeho Sean
Published: August 2014

Ileostomy obstruction in pregnancy, although rare, is a significant complication with associated morbidity and mortality. Early studies recommended immediate surgical intervention for cases of ileostomy obstruction in pregnancy. We present a case of ileostomy obstruction at 29-week gestation in which a laparotomy was performed for presumed adhesions. When adhesiolysis failed to resolve the obstruction, it became clear that the obstruction was caused by external compression from the enlarging gravid uterus. The remainder of the pregnancy was successfully managed by daily aspiration of bowel contents using a large bore drainage tube, and total parental nutrition. Recent studies have utilised MRI to distinguish between adhesions and uterine compression as the cause of ileostomy obstruction in pregnancy. In the few cases of obstruction caused by uterine compression, patients have been safely managed with conservative therapy, thereby avoiding the risks of surgery.
Evaluation of hospital factors associated with hospital postoperative venous thromboembolism imaging utilisation practices
Authors: Chung Jeanette W , Ju Mila H , Kinnier Christine V , Haut Elliott R , Baker David W , Bilimoria Karl Y
Published: August 2014

Background

Recent research suggests that hospital rates of postoperative venous thromboembolism (VTE) are subject to surveillance bias: the more hospitals ‘look for’ VTE, the more VTE they find. However, little is known about what drives variation in hospital VTE imaging rates. We conducted an observational study to examine hospital and market characteristics that were associated with hospital-level rates of postoperative VTE imaging, focusing on hospitals with particularly high rates.

Methods

For Medicare beneficiaries undergoing 11 major operations (2009–2010) at 2820 hospitals, hospital-level postoperative VTE imaging use rates were calculated. Hospital characteristics associated with hospital VTE imaging use rates were examined including case severity, size, ownership, VTE process measure adherence, accreditations, staffing, malpractice environment, and county market factors. Associations between explanatory variables and VTE imaging rates were assessed using quantile regressions at the 25th, median, 75th and 90th quantiles.

Results

Mean postoperative VTE imaging rates ranged from 85.26 (SD=67.38) per 1000 discharges in the lowest quartile of hospitals ranked by VTE imaging rates to 168.86 (SD=76.70) in the highest quartile. Drivers of high imaging rates at the 90th quantile were high resident-to-bed ratio (coefficient=51.35, p<0.01), Joint Commission accreditation (coefficient=19.05, p<0.01), presence of other hospitals in the same market with high imaging rates (coefficient=15.29, p<0.01), average case severity (coefficient=11.97, p<0.01), local malpractice costs (coefficient=11.29, p<0.01), and market competition (coefficient=11.03, p<0.01).

Conclusions

Hospital teaching status, resident-to-bed ratio, malpractice environment and local market factors drive hospital postoperative VTE imaging use, suggesting that non-clinical forces predominantly drive hospital VTE imaging practices.
Republished: Creating a safe, reliable hospital at night handover: a case study in implementation science
Authors: McQuillan Annette , Carthey Jane , Catchpole Ken , McCulloch Peter , Ridout Deborah A , Goldman Allan P
Published: August 2014

Background

We developed protocols to handover patients from day to hospital at night (H@N) teams.

Setting

NHS paediatric specialist hospital.

Method

We observed four handover protocols (baseline, Phases 1, 2 and 3) over 2 years. A mixed-method study (observation, interviews, task analysis, prospective risk assessment, document and case note review) explored the impact of different protocols on performance.

Intervention

In Phase 1, a handover protocol was introduced to resolve problems with the baseline H@N handover. Following this intervention, two further revisions to the handover occurred, driven by staff feedback (Phases 2 and 3).

Results

Variations in performance between handover protocols on three process measures, start time efficiency, total length of handover, and number of distractions and interruptions, were identified. Univariate regression analysis showed statistically significant differences between handover protocols on two surrogate outcome measures: number of flagging omissions and the number of out of hours deteriorations (p=0.04 for Phase 3 vs Phase 1 for both measures (CI 1.04 to 4.08; CI 1.03 to 4.33), and for Phase 3 vs Phase 2 (p=0.006 and p=0.001 (CI 1.22 to 5.15; CI 1.62 to 9.0)), respectively). The Phase 1 and 2 handover protocols were effective at identifying patients whose clinical condition warranted review overnight. Performance on both surrogate outcome measures, length of handover and distractions, deteriorated in Phase 3.

Conclusions

A carefully designed prioritisation process within the H@N handover can be effective at flagging acutely unwell patients. However, the protocol we introduced was unsustainable. In a complex healthcare system, sustainable implementation of new processes may be threatened by conflicting goals.