bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrence rates and clinical outcome for dogs with gradeIImast cell tumours with a lowAgNORcount and Ki67 index treated with surgery alone
Authors: Smith J. , Kiupel M. , Farrelly J. , Cohen R. , Olmsted G. , Kirpensteijn J. , Brocks B. , Post G. 
Published: February 2015

AbstractGradeIImast cell tumours (MCT) are tumours with variable biologic behaviour. Multiple factors have been associated with outcome, including proliferation markers. The purpose of this study was to determine if extent of surgical excision affects recurrence rate in dogs with gradeII MCTwith low proliferation activity, determined by Ki67 and argyrophilic nucleolar organising regions (AgNOR). Eighty‐six dogs with cutaneousMCTwere evaluated. All dogs had surgical excision of theirMCTwith a low Ki67 index and combinedAgNORxKi67(Ag67) values. Twenty‐three (27%) dogs developed local or distant recurrence during the median follow‐up time. Of these dogs, six (7%) had local recurrence, one had complete and five had incomplete histologic margins. This difference in recurrence rates between dogs with complete and incomplete histologic margins was not significant. On the basis of this study, ancillary therapy may not be necessary for patients with incompletely excised gradeII MCTwith low proliferation activity.
Differential CYP 2D6 Metabolism Alters Primaquine Pharmacokinetics
Authors: Potter Brittney M. J. , Xie Lisa H. , Vuong Chau , Zhang Jing , Zhang Ping , Duan Dehui , Luong Thu-Lan T. , Bandara Herath H. M. T. , Dhammika Nanayakkara N. P. , Tekwani Babu L. , Walker Larry A. , Nolan Christina K. , Sciotti Richard J. , Zottig Victor E. , Smith Philip L. , Paris Robert M. , Read Lisa T. , Li Qigui , Pybus Brandon S. , Sousa Jason C. , Reichard Gregory A. , Marcsisin Sean R. 
Published: February 2015

ABSTRACT

Primaquine (PQ) metabolism by the cytochrome P450 (CYP) 2D family of enzymes is required for antimalarial activity in both humans (2D6) and mice (2D). Human CYP 2D6 is highly polymorphic, and decreased CYP 2D6 enzyme activity has been linked to decreased PQ antimalarial activity. Despite the importance of CYP 2D metabolism in PQ efficacy, the exact role that these enzymes play in PQ metabolism and pharmacokinetics has not been extensively studied
in vivo
. In this study, a series of PQ pharmacokinetic experiments were conducted in mice with differential CYP 2D metabolism characteristics, including wild-type (WT), CYP 2D knockout (KO), and humanized CYP 2D6 (KO/knock-in [KO/KI]) mice. Plasma and liver pharmacokinetic profiles from a single PQ dose (20 mg/kg of body weight) differed significantly among the strains for PQ and carboxy-PQ. Additionally, due to the suspected role of phenolic metabolites in PQ efficacy, these were probed using reference standards. Levels of phenolic metabolites were highest in mice capable of metabolizing CYP 2D6 substrates (WT and KO/KI 2D6 mice). PQ phenolic metabolites were present in different quantities in the two strains, illustrating species-specific differences in PQ metabolism between the human and mouse enzymes. Taking the data together, this report furthers understanding of PQ pharmacokinetics in the context of differential CYP 2D metabolism and has important implications for PQ administration in humans with different levels of CYP 2D6 enzyme activity.
Colostrum Hexasaccharide, a Novel Staphylococcus aureus Quorum-Sensing Inhibitor
Authors: Srivastava A. , Singh B. N. , Deepak D. , Rawat A. K. S. , Singh B. R. 
Published: February 2015

ABSTRACT

The discovery of quorum-sensing (QS) systems regulating antibiotic resistance and virulence factors (VFs) has afforded a novel opportunity to prevent bacterial pathogenicity. Dietary molecules have been demonstrated to attenuate QS circuits of bacteria. But, to our knowledge, no study exploring the potential of colostrum hexasaccharide (CHS) in regulating QS systems has been published. In this study, we analyzed CHS for inhibiting QS signaling in
Staphylococcus aureus
. We isolated and characterized CHS from mare colostrum by high-performance thin-layer chromatography (HPTLC), reverse-phase high-performance liquid chromatography evaporative light-scattering detection (RP-HPLC-ELSD),
1
H and
13
C nuclear magnetic resonance (NMR), and electrospray ionization mass spectrometry (ESI-MS). Antibiofilm activity of CHS against
S. aureus
and its possible interference with bacterial QS systems were determined. The inhibition and eradication potentials of the biofilms were studied by microscopic analyses and quantified by 96-well-microtiter-plate assays. Also, the ability of CHS to interfere in bacterial QS by degrading acyl-homoserine lactones (AHLs), one of the most studied signal molecules for Gram-negative bacteria, was evaluated. The results revealed that CHS exhibited promising inhibitory activities against QS-regulated secretion of VFs, including spreading ability, hemolysis, protease, and lipase activities, when applied at a rate of 5 mg/ml. The results of biofilm experiments indicated that CHS is a strong inhibitor of biofilm formation and also has the ability to eradicate it. The potential of CHS to interfere with bacterial QS systems was also examined by degradation of AHLs. Furthermore, it was documented that CHS decreased antibiotic resistance in
S. aureus
. The results thus give a lead that mare colostrum can be a promising source for isolating a next-generation antibacterial.
Two Mechanisms of Killing of Pseudomonas aeruginosa by Tobramycin Assessed at Multiple Inocula via Mechanism-Based Modeling
Authors: Bulitta Jürgen B. , Ly Neang S. , Landersdorfer Cornelia B. , Wanigaratne Nicholin A. , Velkov Tony , Yadav Rajbharan , Oliver Antonio , Martin Lisandra , Shin Beom Soo , Forrest Alan , Tsuji Brian T. 
Published: February 2015

ABSTRACT

Bacterial resistance is among the most serious threats to human health globally, and many bacterial isolates have emerged that are resistant to all antibiotics in monotherapy. Aminoglycosides are often used in combination therapies against severe infections by multidrug-resistant bacteria. However, models quantifying different antibacterial effects of aminoglycosides are lacking. While the mode of aminoglycoside action on protein synthesis has often been studied, their disruptive action on the outer membrane of Gram-negative bacteria remains poorly characterized. Here, we developed a novel quantitative model for these two mechanisms of aminoglycoside action, phenotypic tolerance at high bacterial densities, and adaptive bacterial resistance in response to an aminoglycoside (tobramycin) against three
Pseudomonas aeruginosa
strains. At low-intermediate tobramycin concentrations (<4 mg/liter), bacterial killing due to the effect on protein synthesis was most important, whereas disruption of the outer membrane was the predominant killing mechanism at higher tobramycin concentrations (≥8 mg/liter). The extent of killing was comparable across all inocula; however, the rate of bacterial killing and growth was substantially lower at the 10
8.9
CFU/ml inoculum than that at the lower inocula. At 1 to 4 mg/liter tobramycin for strain PAO1-RH, there was a 0.5- to 6-h lag time of killing that was modeled via the time to synthesize hypothetical lethal protein(s). Disruption of the outer bacterial membrane by tobramycin may be critical to enhance the target site penetration of antibiotics used in synergistic combinations with aminoglycosides and thereby combat multidrug-resistant bacteria. The two mechanisms of aminoglycoside action and the new quantitative model hold great promise to rationally design novel, synergistic aminoglycoside combination dosage regimens.
Sustained Release of a Novel Anti-Quorum-Sensing Agent against Oral Fungal Biofilms
Authors: Feldman Mark , Shenderovich Julia , Al-Quntar Abed Al Aziz , Friedman Michael , Steinberg Doron 
Published: February 2015

ABSTRACT

Thiazolidinedione-8 (S-8) has recently been identified as a potential anti-quorum-sensing/antibiofilm agent against bacteria and fungi. Based on these results, we investigated the possibility of incorporating S-8 in a sustained-release membrane (SRM) to increase its pharmaceutical potential against
Candida albicans
biofilm. We demonstrated that SRM containing S-8 inhibits fungal biofilm formation in a time-dependent manner for 72 h, due to prolonged release of S-8. Moreover, the SRM effectively delivered the agent in its active form to locations outside the membrane reservoir. In addition, eradication of mature biofilm by the SRM containing S-8 was also significant. Of note, S-8-containing SRM affected the characteristics of mature
C. albicans
biofilm, such as thickness, exopolysaccharide (EPS) production, and morphogenesis of fungal cells. The concept of using an antibiofilm agent with no antifungal activity incorporated into a sustained-release delivery system is new in medicine and dentistry. This concept of an SRM containing a quorum-sensing quencher with an antibiofilm effect could pave the way for combating oral fungal infectious diseases.
Tuberculous Spondylitis in Russia and Prominent Role of Multidrug-Resistant Clone Mycobacterium tuberculosis Beijing B0/W148
Authors: Vyazovaya Anna , Mokrousov Igor , Solovieva Natalia , Mushkin Alexander , Manicheva Olga , Vishnevsky Boris , Zhuravlev Viacheslav , Narvskaya Olga 
Published: February 2015

ABSTRACT

Extrapulmonary and, in particular, spinal tuberculosis (TB) constitutes a minor but significant part of the total TB incidence. In spite of this, almost no studies on the genetic diversity and drug resistance of
Mycobacterium tuberculosis
isolates from spinal TB patients have been published to date. Here, we report results of the first Russian and globally largest molecular study of
M. tuberculosis
isolates recovered from patients with tuberculous spondylitis (TBS). The majority of 107 isolates were assigned to the Beijing genotype (
n
= 80); the other main families were T (
n
= 11), Ural (
n
= 7), and LAM (
n
= 4). Multidrug resistance (MDR) was more frequently found among Beijing (90.5%) and, intriguingly, Ural (71.4%) isolates than other genotypes (5%;
P
< 0.001). The extremely drug-resistant (XDR) phenotype was exclusively found in the Beijing isolates (
n
= 7). A notable prevalence of the
rpoB531
and
katG315
mutations in Beijing strains that were similarly high in both TBS (this study) and published pulmonary TB (PTB) samples from Russia shows that TBS and PTB Beijing strains follow the same paradigm of acquisition of rifampin (RIF) and isoniazid (INH) resistance. The 24-locus mycobacterial interspersed repetitive unit–variable-number tandem-repeat (MIRU-VNTR) subtyping of 80 Beijing isolates further discriminated them into 24 types (Hunter Gaston index [HGI] = 0.83); types 100-32 and 94-32 represented the largest groups. A genotype of Russian successful clone B0/W148 was identified in 30 of 80 Beijing isolates. In conclusion, this study highlighted a crucial impact of the Beijing genotype and the especially prominent role of its MDR-associated successful clone B0/W148 cluster in the development of spinal MDR-TB in Russian patients.
Rapid Drug Tolerance and Dramatic Sterilizing Effect of Moxifloxacin Monotherapy in a Novel Hollow-Fiber Model of Intracellular Mycobacterium kansasii Disease
Authors: Srivastava Shashikant , Pasipanodya Jotam , Sherman Carleton M. , Meek Claudia , Leff Richard , Gumbo Tawanda 
Published: February 2015

ABSTRACT

Mycobacterium kansasii
is the second most common mycobacterial cause of lung disease. Standard treatment consists of rifampin, isoniazid, and ethambutol for at least 12 months after negative sputum. Thus, shorter-duration therapies are needed. Moxifloxacin has good MICs for
M. kansasii
. However, good preclinical models to identify optimal doses currently are lacking. We developed a novel hollow fiber system model of intracellular
M. kansasii
infection. We indexed the efficacy of the standard combination regimen, which was a kill rate of −0.08 ± 0.05 log
10
CFU/ml/day (
r
2
= 0.99). We next performed moxifloxacin dose-effect and dose-scheduling studies at a half-life of 11.1 ± 6.47 h. Some systems also were treated with the efflux pump inhibitor reserpine. The highest moxifloxacin exposure, as well as lower exposures plus reserpine, sterilized the cultures by day 7. This suggests that efflux pump-mediated tolerance at low ratios of the area under the concentration-time curve from 0 to 24 h (AUC
0
–
24
) to MICs is an early bacterial defense mechanism but is overcome by higher exposures. The highest rate of moxifloxacin monotherapy sterilization was −0.82 ± 0.15 log
10
CFU/ml/day (
r
2
= 0.97). The moxifloxacin exposure associated with 80% of maximal kill (EC
80
) was an AUC
0–24
/MIC of 317 (the non-protein-bound moxifloxacin AUC
0–24
/MIC was 158.5). We performed Monte Carlo simulations of 10,000 patients in order to identify the moxifloxacin dose that would achieve or exceed the EC
80
. The simulations revealed an optimal moxifloxacin dose of 800 mg a day. The MIC susceptibility breakpoint at this dose was 0.25 mg/liter. Thus, moxifloxacin, at high enough doses, is suitable to study in patients for the potential to add rapid sterilization to the standard regimen.
Update on Linezolid
In Vitro
Activity through the Zyvox Annual Appraisal of Potency and Spectrum Program, 2013
Authors: Mendes Rodrigo E. , Hogan Patricia A. , Streit Jennifer M. , Jones Ronald N. , Flamm Robert K. 
Published: February 2015

ABSTRACT

Linezolid showed MIC
50
s and MIC
90
s of 1 μg/ml (for both) against
Staphylococcus aureus
. Two
S. aureus
strains exhibited higher MICs (4 to 8 μg/ml) caused by
cfr
and/or target site mutations, including the first detection of
cfr
in Poland. Linezolid (MIC
50
and MIC
90
, 0.5 and 1 μg/ml) had potent MICs against coagulase-negative staphylococci (CoNS). Four CoNS had MICs of 16 to 128 μg/ml due to alterations in 23S rRNA and/or L3/L4. Linezolid inhibited all enterococci and streptococci at ≤2 μg/ml, except for one
Enterococcus faecium
strain (MIC, 8 μg/ml; G2576T [
Escherichia coli
numbering] mutation).
Efficacy of Postexposure Therapy against Glanders in Mice
Authors: Waag David M. 
Published: February 2015

ABSTRACT

Burkholderia mallei
, the causative agent of glanders, is a CDC Tier 1 Select Agent for which there is no preventive vaccine and antibiotic therapy is difficult. In this study, we show that a combination of vaccination using killed cellular vaccine and therapy using moxifloxacin, azithromycin, or sulfamethoxazole-trimethoprim can protect BALB/c mice from lethal infection even when given 5 days after infectious challenge. Vaccination only, or antibiotic therapy only, was not efficacious. Although antibiotics evaluated experimentally can protect when given before or 1 day after challenge, this time course is not realistic in the cases of natural infection or biological attack, when the patient seeks treatment after symptoms develop or after a biological attack has been confirmed and the agent has been identified. Antibiotics can be efficacious after a prolonged interval between exposure and treatment, but only if the animals were previously vaccinated.
Decreasing Global Transcript Levels over Time Suggest that Phytoplasma Cells Enter Stationary Phase during Plant and Insect Colonization
Authors: Pacifico D. , Galetto L. , Rashidi M. , Abbà S. , Palmano S. , Firrao G. , Bosco D. , Marzachì C. 
Published: January 2015

ABSTRACTTo highlight different transcriptional behaviors of the phytoplasma in the plant and animal host, expression of 14 genes of “CandidatusPhytoplasma asteris,” chrysanthemum yellows strain, was investigated at different times following the infection of a plant host (Arabidopsis thaliana) and two insect vector species (Macrosteles quadripunctulatusandEuscelidius variegatus). Target genes were selected among those encoding antigenic membrane proteins, membrane transporters, secreted proteins, and general enzymes. Transcripts were detected for all analyzed genes in the three hosts; in particular, those encoding the antigenic membrane protein Amp, elements of the mechanosensitive channel, and two of the four secreted proteins (SAP54 and TENGU) were highly accumulated, suggesting that they play important roles in phytoplasma physiology during the infection cycle. Most transcripts were present at higher abundance in the plant host than in the insect hosts. Generally, transcript levels of the selected genes decreased significantly during infection ofA. thalianaandM. quadripunctulatusbut were more constant inE. variegatus. Such decreases may be explained by the fact that only a fraction of the phytoplasma population was transcribing, while the remaining part was aging to a stationary phase. This strategy might improve long-term survival, thereby increasing the likelihood that the pathogen may be acquired by a vector and/or inoculated to a healthy plant.
Nitric Oxide Treatment for the Control of Reverse Osmosis Membrane Biofouling
Authors: Barnes Robert J. , Low Jiun Hui , Bandi Ratnaharika R. , Tay Martin , Chua Felicia , Aung Theingi , Fane Anthony G. , Kjelleberg Staffan , Rice Scott A. 
Published: January 2015

ABSTRACT
Biofouling remains a key challenge for membrane-based water treatment systems. This study investigated the dispersal potential of the nitric oxide (NO) donor compound, PROLI NONOate, on single- and mixed-species biofilms formed by bacteria isolated from industrial membrane bioreactor and reverse osmosis (RO) membranes. The potential of PROLI NONOate to control RO membrane biofouling was also examined. Confocal microscopy revealed that PROLI NONOate exposure induced biofilm dispersal in all but two of the bacteria tested and successfully dispersed mixed-species biofilms. The addition of 40 μM PROLI NONOate at 24-h intervals to a laboratory-scale RO system led to a 92% reduction in the rate of biofouling (pressure rise over a given period) by a bacterial community cultured from an industrial RO membrane. Confocal microscopy and extracellular polymeric substances (EPS) extraction revealed that PROLI NONOate treatment led to a 48% reduction in polysaccharides, a 66% reduction in proteins, and a 29% reduction in microbial cells compared to the untreated control. A reduction in biofilm surface coverage (59% compared to 98%, treated compared to control) and average thickness (20 μm compared to 26 μm, treated compared to control) was also observed. The addition of PROLI NONOate led to a 22% increase in the time required for the RO module to reach its maximum transmembrane pressure (TMP), further indicating that NO treatment delayed fouling. Pyrosequencing analysis revealed that the NO treatment did not significantly alter the microbial community composition of the membrane biofilm. These results present strong evidence for the application of PROLI NONOate for prevention of RO biofouling.
Multifactorial Effects of Ambient Temperature, Precipitation, Farm Management, and Environmental Factors Determine the Level of Generic Escherichia coli Contamination on Preharvested Spinach
Authors: Park Sangshin , Navratil Sarah , Gregory Ashley , Bauer Arin , Srinath Indumathi , Szonyi Barbara , Nightingale Kendra , Anciso Juan , Jun Mikyoung , Han Daikwon , Lawhon Sara , Ivanek Renata 
Published: January 2015

ABSTRACT

A repeated cross-sectional study was conducted to identify farm management, environment, weather, and landscape factors that predict the count of generic
Escherichia coli
on spinach at the preharvest level.
E. coli
was enumerated for 955 spinach samples collected on 12 farms in Texas and Colorado between 2010 and 2012. Farm management and environmental characteristics were surveyed using a questionnaire. Weather and landscape data were obtained from National Resources Information databases. A two-part mixed-effect negative binomial hurdle model, consisting of a logistic and zero-truncated negative binomial part with farm and date as random effects, was used to identify factors affecting
E. coli
counts on spinach. Results indicated that the odds of a contamination event (non-zero versus zero counts) vary by state (odds ratio [OR] = 108.1). Odds of contamination decreased with implementation of hygiene practices (OR = 0.06) and increased with an increasing average precipitation amount (mm) in the past 29 days (OR = 3.5) and the application of manure (OR = 52.2). On contaminated spinach,
E. coli
counts increased with the average precipitation amount over the past 29 days. The relationship between
E. coli
count and the average maximum daily temperature over the 9 days prior to sampling followed a quadratic function with the highest bacterial count at around 24°C. These findings indicate that the odds of a contamination event in spinach are determined by farm management, environment, and weather factors. However, once the contamination event has occurred, the count of
E. coli
on spinach is determined by weather only.
Microbial Safety and Sanitary Quality of Strawberry Primary Production in Belgium: Risk Factors for Salmonella and Shiga Toxin-Producing Escherichia coli Contamination
Authors: Delbeke Stefanie , Ceuppens Siele , Hessel Claudia Titze , Castro Irene , Jacxsens Liesbeth , De Zutter Lieven , Uyttendaele Mieke 
Published: January 2015

ABSTRACT

Strawberries are an important fruit in Belgium in both production and consumption, but little information is available about the presence of
Salmonella
and Shiga toxin-producing
Escherichia coli
(STEC) in these berries, the risk factors in agricultural production, and possible specific mitigation options. In 2012, a survey was undertaken of three soil and three soilless cultivation systems in Belgium. No
Salmonella
spp. were isolated. No STEC was detected in the strawberry samples (0 of 72), but STEC was detected by PCR in 11 of 78 irrigation water and 2 of 24 substrate samples. Culture isolates were obtained for 2 of 11 PCR-positive irrigation water samples and 2 of 2 substrate samples. Multivariable logistic regression analysis revealed elevated generic
E. coli
numbers (the odds ratio [OR] for a 1 log increase being 4.6) as the most important risk factor for STEC, together with the berry-picking season (elevated risk in summer). The presence of generic
E. coli
in the irrigation water (≥1 CFU per 100 ml) was mainly influenced by the type of irrigation water (collected rainfall water stored in ponds was more often contaminated than groundwater pumped from boreholes [OR = 5.8]) and the lack of prior treatment (untreated water versus water subjected to sand filtration prior to use [OR = 19.2]). The follow-up study in 2013 at one of the producer locations indicated cattle to be the most likely source of STEC contamination of the irrigation water.