bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discrimination between Native and Tn
6010
-Associated
oqxAB
in Klebsiella spp., Raoultella spp., and other Enterobacteriaceae by Using a Two-Step Strategy
Authors: Guillard Thomas , Lebreil Anne-Laure , Hansen Lars Hestbjerg , Kisserli Aymric , Berger Sibel , Lozniewski Alain , Alauzet Corentine , de Champs Christophe 
Published: June 2015

ABSTRACT

We developed a two-step PCR-based strategy to detect genes encoding OqxAB, allowing a specific assignment of Tn
6010
-associated
oqxAB
in
Enterobacteriaceae
. Chromosomal location in this setup was confirmed by hybridization with I-
Ceu
I-restricted genomes. This approach led us to find that
Klebsiella
sp. and
Raoultella
sp. reference strains chromosomally carried
oqxAB
.
Pharmacodynamics of Fosfomycin: Insights into Clinical Use for Antimicrobial Resistance
Authors: Docobo-Pérez F. , Drusano G. L. , Johnson A. , Goodwin J. , Whalley S. , Ramos-Martín V. , Ballestero-Tellez M. , Rodriguez-Martinez J. M. , Conejo M. C. , van Guilder M. , Rodríguez-Baño J. , Pascual A. , Hope W. W. 
Published: June 2015

ABSTRACT

The aim of this study was to improve the understanding of the pharmacokinetic-pharmacodynamic relationships of fosfomycin against extended-spectrum beta-lactamase (ESBL)-producing
Escherichia coli
strains that have different fosfomycin MICs. Our methods included the use of a hollow fiber infection model with three clinical ESBL-producing
E. coli
strains. Human fosfomycin pharmacokinetic profiles were simulated over 4 days. Preliminary studies conducted to determine the dose ranges, including the dose ranges that suppressed the development of drug-resistant mutants, were conducted with regimens from 12 g/day to 36 g/day. The combination of fosfomycin at 4 g every 8 h (q8h) and meropenem at 1 g/q8h was selected for further assessment. The total bacterial population and the resistant subpopulations were determined. No efficacy was observed against the Ec42444 strain (fosfomycin MIC, 64 mg/liter) at doses of 12, 24, or 36 g/day. All dosages induced at least initial bacterial killing against Ec46 (fosfomycin MIC, 1 mg/liter). High-level drug-resistant mutants appeared in this strain in response to 12, 15, and 18 g/day. In the study arms that included 24 g/day, once or in a divided dose, a complete extinction of the bacterial inoculum was observed. The combination of meropenem with fosfomycin was synergistic for bacterial killing and also suppressed all fosfomycin-resistant clones of Ec2974 (fosfomycin MIC, 1 mg/liter). We conclude that fosfomycin susceptibility breakpoints (≤64 mg/liter according to CLSI [for
E. coli
urinary tract infections only]) should be revised for the treatment of serious systemic infections. Fosfomycin can be used to treat infections caused by organisms that demonstrate lower MICs and lower bacterial densities, although relatively high daily dosages (i.e., 24 g/day) are required to prevent the emergence of bacterial resistance. The ratio of the area under the concentration-time curve for the free, unbound fraction of fosfomycin versus the MIC (
f
AUC/MIC) appears to be the dynamically linked index of suppression of bacterial resistance. Fosfomycin with meropenem can act synergistically against
E. coli
strains in preventing the emergence of fosfomycin resistance.
In Vivo
Biocompatibility and
In Vitro
Efficacy of Antimicrobial Gendine-Coated Central Catheters
Authors: Jamal Mohamed A. , Hachem Ray Y. , Rosenblatt Joel , McArthur Mark J. , Felix Edd , Jiang Ying , Tailor Ramesh C. , Raad Issam 
Published: June 2015

ABSTRACT

Antimicrobial peripherally inserted central catheters (PICCs) might reduce the incidence of central line-associated bloodstream infections (CLABSI). We tested the biocompatibility of a novel gendine-coated (combination of chlorhexidine [CHX] and gentian violet [GV]) PICC in a rabbit intravascular model and tested antimicrobial efficacy in comparison with commercially available minocycline/rifampin (M/R)- and CHX-treated PICCs in an
in vitro
biofilm colonization model. Gendine-coated and uncoated control PICCs were inserted in the jugular veins of rabbits for 4 days. Histopathological analysis was performed at the end of the 4-day period, and circulating levels of CHX and GV in the blood were measured at different time points using liquid chromatography-mass spectrometry. The antimicrobial efficacy of the PICCs was tested following simulated intravascular indwells of 24 h and 1 week against clinical isolates of methicillin-resistant
Staphylococcus aureus
, vancomycin-resistant enterococci,
Pseudomonas aeruginosa
,
Escherichia coli
,
Acinetobacter baumannii
,
Enterobacter cloacae
,
Candida albicans
, and
Candida glabrata
. Rabbits implanted with gendine-coated PICCs exhibited reduced levels of thrombosis and inflammation compared to those of the rabbits with uncoated controls. No GV was detected in blood samples over the entire study period, and trace concentrations of CHX were detected. The gendine-coated PICCs completely prevented the adherence of all pathogens from 24 h to 1 week (
P
≤ 0.001), while M/R-treated, CHX-treated, and control PICCs did not. Gendine-coated PICCs were highly effective in preventing biofilm formation of multidrug-resistant pathogenic bacteria and fungi. Gendine-coated PICCs were biocompatible in an intravascular setting. Further, the pharmacokinetic testing established that acute systemic exposures of CHX and GV from the gendine-coated catheters were well within safe levels.
Bacterial Internalization, Localization, and Effectors Shape the Epithelial Immune Response during Shigella flexneri Infection
Authors: Lippmann Juliane , Gwinner Frederik , Rey Camille , Tamir Uyanga , Law Helen K. W. , Schwikowski Benno , Enninga Jost 
Published: June 2015

ABSTRACT

Intracellular pathogens are differentially sensed by the compartmentalized host immune system. Nevertheless, gene expression studies of infected cells commonly average the immune responses, neglecting the precise pathogen localization. To overcome this limitation, we dissected the transcriptional immune response to
Shigella flexneri
across different infection stages in bulk and single cells. This identified six distinct transcriptional profiles characterizing the dynamic, multilayered host response in both bystander and infected cells. These profiles were regulated by external and internal danger signals, as well as whether bacteria were membrane bound or cytosolic. We found that bacterial internalization triggers a complex, effector-independent response in bystander cells, possibly to compensate for the undermined host gene expression in infected cells caused by bacterial effectors, particularly OspF. Single-cell analysis revealed an important bacterial strategy to subvert host responses in infected cells, demonstrating that OspF disrupts concomitant gene expression of proinflammatory, apoptosis, and stress pathways within cells. This study points to novel mechanisms through which bacterial internalization, localization, and injected effectors orchestrate immune response transcriptional signatures.
From (p)ppGpp to (pp)pGpp: Characterization of Regulatory Effects of pGpp Synthesized by the Small Alarmone Synthetase of Enterococcus faecalis
Authors: Gaca Anthony O. , Kudrin Pavel , Colomer-Winter Cristina , Beljantseva Jelena , Liu Kuanqing , Anderson Brent , Wang Jue D. , Rejman Dominik , Potrykus Katarzyna , Cashel Michael , Hauryliuk Vasili , Lemos José A 
Published: June 2015

ABSTRACT

The bacterial stringent response (SR) is a conserved stress tolerance mechanism that orchestrates physiological alterations to enhance cell survival. This response is mediated by the intracellular accumulation of the alarmones pppGpp and ppGpp, collectively called (p)ppGpp. In
Enterococcus faecalis
, (p)ppGpp metabolism is carried out by the bifunctional synthetase/hydrolase
E. faecalis
Rel (Rel
Ef
) and the small alarmone synthetase (SAS) RelQ
Ef
. Although Rel is the main enzyme responsible for SR activation in
Firmicutes
, there is emerging evidence that SASs can make important contributions to bacterial homeostasis. Here, we showed that RelQ
Ef
synthesizes ppGpp more efficiently than pppGpp without the need for ribosomes, tRNA, or mRNA. In addition to (p)ppGpp synthesis from GDP and GTP, RelQ
Ef
also efficiently utilized GMP to form GMP 3′-diphosphate (pGpp). Based on this observation, we sought to determine if pGpp exerts regulatory effects on cellular processes affected by (p)ppGpp. We found that pGpp, like (p)ppGpp, strongly inhibits the activity of
E. faecalis
enzymes involved in GTP biosynthesis and, to a lesser extent, transcription of
rrnB
by
Escherichia coli
RNA polymerase. Activation of
E. coli
RelA synthetase activity was observed in the presence of both pGpp and ppGpp, while RelQ
Ef
was activated only by ppGpp. Furthermore, enzymatic activity of RelQ
Ef
is insensitive to relacin, a (p)ppGpp analog developed as an inhibitor of “long” RelA/SpoT homolog (RSH) enzymes. We conclude that pGpp can likely function as a bacterial alarmone with target-specific regulatory effects that are similar to what has been observed for (p)ppGpp.

IMPORTANCE
Accumulation of the nucleotide second messengers (p)ppGpp in bacteria is an important signal regulating genetic and physiological networks contributing to stress tolerance, antibiotic persistence, and virulence. Understanding the function and regulation of the enzymes involved in (p)ppGpp turnover is therefore critical for designing strategies to eliminate the protective effects of this molecule. While characterizing the (p)ppGpp synthetase RelQ of
Enterococcus faecalis
(RelQ
Ef
), we found that, in addition to (p)ppGpp, RelQ
Ef
is an efficient producer of pGpp (GMP 3′-diphosphate).
In vitro
analysis revealed that pGpp exerts complex, target-specific effects on processes known to be modulated by (p)ppGpp. These findings provide a new regulatory feature of RelQ
Ef
and suggest that pGpp may represent a new member of the (pp)pGpp family of alarmones.
Trial of Intensive Acupuncture for Smoking Cessation: A Pilot Study
Authors: McFadden David D , Chon Tony Y , Croghan Ivana T , Schroeder Darrell R , Mallory Molly J , Ebbert Jon O , Hays J Taylor 
Published: June 2015

Background Despite the significant decline in smoking rates in the USA over the last 50 years, 42 million Americans continue to smoke. Although the combination of behavioural counselling with FDA-approved medications offers the best evidence-based treatment approach, 12-month relapse rates remain at >60%. Both healthcare providers and patients are searching for alternative treatment options. Most acupuncture trials have yielded poor results for smoking cessation; however, most trials have not used an intense treatment protocol and maintained treatment for at least 12 weeks. Methods We designed a pilot study to address these methodological problems. Twenty-eight smokers were recruited to attend two 1 h acupuncture sessions weekly for 12 weeks. Primary endpoints included completion rate, acceptability of the protocol and side effects. Secondary endpoints included carbon monoxide (CO)-confirmed, 7-day point prevalence quit rates at 12 weeks and 26 weeks. Results Sixteen of the 28 patients enrolled (57%) completed 12 weeks of treatment. Of the 17 patients who completed the end-of-study questionnaire, 94% (16/17) rated the programme as helpful, and 82% noted they would recommend it to friends for smoking cessation. Three of the 28 who initially enrolled in the study were confirmed abstinent at 12 weeks (10.7%); one of the 28 (3.6%) was abstinent at 26 weeks. Conclusions A larger study with a slightly less rigorous and more acceptable treatment protocol is feasible and should be considered.
What matters most for end-of-life care? Perspectives from community-based palliative care providers and administrators
Authors: Mistry Bina , Bainbridge Daryl , Bryant Deanna , Tan Toyofuku Sue , Seow Hsien 
Published: June 2015

ObjectivesThere has been little research conducted to understand the essential meaning of quality, community-based, end-of-life (EOL) care, despite the expansion of these services. The purpose of this study was to define what matters most for EOL care from the perspective of a diverse range of palliative care providers in the community who have daily encounters with death and dying.MethodsWe used interviews to explore the perceptions of providers and administrators from 14 specialised palliative care teams in Ontario, Canada. Participants were prompted with the question ‘What matters most for EOL care?’ Responses were analysed using a phenomenological approach to derive themes depicting the universal essence of EOL care.ResultsData from 107 respondents were obtained and analysed, from which 40 formulated concepts emerged; these were further grouped into 9 themes. Of the respondents, 39% were nurses, 19% physicians, 27% were supervisors or executives and 15% other. The most predominate concept was thatPatient's Wishes are Fulfilled, cited by almost half the respondents. The most prominent themes wereAddressing the Non-physical Needs,Healthcare Teams’ Nature of Palliative Care Delivery,Patient Wishes are Honoured,Addressing the Physical Needs,Preparing for and Accepting Death,Communication and Relationship Development, andInvolving and Supporting the Family.Conclusions9 critical domains of EOL care evolved from the interviews, indicating that quality EOL care extends beyond managing physical pain, but includes a holistic perspective of care, a healthcare team dedicated to the EOL journey and a patient-centred pathway. Tailoring the provision of care to consider these important elements plays a critical role in supporting a positive EOL experience for patients and families.
Portal inflammation during NAFLD is frequent and associated with the early phases of putative hepatic progenitor cell activation
Authors: Carotti Simone , Vespasiani-Gentilucci Umberto , Perrone Giuseppe , Picardi Antonio , Morini Sergio 
Published: June 2015

AimsWe investigated whether portal tract inflammation observed in non-alcoholic fatty liver disease (NAFLD) is associated with hepatic progenitor cell compartment activation, as thoroughly evaluated with different markers of the staminal lineage.MethodsFifty-two patients with NAFLD were studied. NAFLD activity score, fibrosis and portal inflammation were histologically evaluated. Putative hepatic progenitor cells, intermediate hepatobiliary cells and bile ductules/interlobular bile ducts were evaluated by immunohistochemistry for cytokeratin (CK)-7, CK-19 and epithelial cell adhesion molecule (EpCAM), and a hepatic progenitor cell compartment score was derived. Hepatic stellate cell and myofibroblast activity was determined by immunohistochemistry for α-smooth muscle actin.ResultsPortal inflammation was absent in a minority of patients, mild in 40% of cases and more than mild in about half of patients, showing a strong correlation with fibrosis (r=0.76, p<0.001). Portal inflammation correlated with CK-7-counted putative hepatic progenitor cells (r=0.48, p<0.001), intermediate hepatobiliary cells (r=0.6, p<0.001) and bile ductules/interlobular bile ducts (r=0.6, p<0.001), and with the activity of myofibroblasts (r=0.5, p<0.001). Correlations were confirmed when elements were counted by immunostaining for CK-19 and EpCAM. Lobular inflammation, ballooning, myofibroblast activity and hepatic progenitor cell compartment activation were associated with portal inflammation by univariate analysis. In the multivariate model, the only variable independently associated with portal inflammation was hepatic progenitor cell compartment activation (OR 3.7, 95% CI 1.1 to 12.6).ConclusionsPortal inflammation is frequent during NAFLD and strongly associated with activation of putative hepatic progenitor cells since the first steps of their differentiation, portal myofibroblast activity and fibrosis.
Routine diversion of patients with STEMI to high-volume PCI centres: modelling the financial impact on referral hospitals
Authors: Pathak Elizabeth Barnett , Comins Meg M , Forsyth Colin J , Strom Joel A 
Published: June 2015

ObjectiveTo quantify possible revenue losses from proposed ST-elevation myocardial infarction (STEMI) patient diversion policies for small hospitals that lack high-volume percutaneous coronary intervention (PCI) capability status (ie, ‘STEMI referral hospitals’).BackgroundNegative financial impacts on STEMI referral hospitals have been discussed as an important barrier to implementing regional STEMI bypass/transfer protocols. However, there is little empirical data available that directly quantifies this potential financial impact.MethodsUsing detailed financial charges from Florida hospital discharge data, we examined the potential negative financial impact on 112 STEMI referral hospitals from losing all inpatient STEMI revenue. The main outcome was projected revenue loss (PRL), defined as total annual patient with STEMI charges as a proportion of total annual charges for all patients. We hypothesised that for most community hospitals (>90%), STEMI revenue represented only a small fraction of total revenue (<1%). We further examined the financial impact of the ‘worst case’ scenario of loss of all acute coronary syndrome (ACS) (ie, chest pain) patients.ResultsPRLs were $0.33 for every $100 of patient revenue statewide for STEMI and $1.73 for ACS. At the individual hospital level, the 90th centile PRL was $0.74 for STEMI and $2.77 for ACS. PRLs for STEMI were not greater in rural areas compared with major metropolitan areas. Hospital revenue centres that would be most impacted by loss of patients with STEMI were cardiology procedures and intensive care units.ConclusionsLoss of patient with STEMI revenues would result in only a small financial impact on STEMI referral hospitals in Florida under proposed STEMI diversion/rapid transfer protocols. However, spillover loss of patients with ACS would increase revenue loss for many hospitals.
Introduction of the use of thermography and thermometry in the diagnosis of uveitis in horses: a pilot project
Authors: Rushton J O , Tichy A , Nell B 
Published: June 2015

Aims and objectivesTo date assessment of changes in ocular temperature, as a hallmark of uveitis in horses has not been determined. Therefore the aim of the current study was to determine whether ocular temperature is increased in acute uveitic eyes compared with non‐uveitic eyes, and to compare an affordable thermometry device with a thermography device.Material and methodsOcular temperatures of both eyes of five horses with acute unilateral uveitis and 10 normal horses were measured using thermometry and thermography. Presence and absence of acute uveitis were diagnosed through a complete ophthalmological examination. Ambient temperature and core body temperature were also recorded.ResultsThe difference in temperatures between uveitic eyes and non‐uveitic eyes was marked but not statistically significant (mean thermography temperature 34.0°C sd±1.6°C and 32.7°C sd±2.4°C, respectively v mean thermometry temperature 34.0°C sd±1.9°C and 31.6°C sd±3.1°C, respectively). No influence of core body temperature on either method was detected. Thermography was less influenced by ambient temperature than was thermometry.ConclusionIn conclusion uveitic eyes are not significantly warmer than non‐uveitic eyes. Despite the lack of significance, a tendency towards increased ocular temperature in uveitic eyes, compared with non‐uveitic eyes was noted. Therefore more research on this topic is warranted.
Investigation of Optical Coherence Microelastography as a Method to Visualize Cancers in Human Breast Tissue
Authors: Kennedy Brendan F. , McLaughlin Robert A. , Kennedy Kelsey M. , Chin Lixin , Wijesinghe Philip , Curatolo Andrea , Tien Alan , Ronald Maxine , Latham Bruce , Saunders Christobel M. , Sampson David D. 
Published: June 2015

AbstractAn accurate intraoperative identification of malignant tissue is a challenge in the surgical management of breast cancer. Imaging techniques that help address this challenge could contribute to more complete and accurate tumor excision, and thereby help reduce the current high reexcision rates without resorting to the removal of excess healthy tissue. Optical coherence microelastography (OCME) is a three-dimensional, high-resolution imaging technique that is sensitive to microscale variations of the mechanical properties of tissue. As the tumor modifies the mechanical properties of breast tissue, OCME has the potential to identify, on the microscale, involved regions of fresh, unstained tissue. OCME is based on the use of optical coherence tomography (OCT) to measure tissue deformation in response to applied mechanical compression. In this feasibility study on 58 ex vivo samples from patients undergoing mastectomy or wide local excision, we demonstrate the performance of OCME as a means to visualize tissue microarchitecture in benign and malignant human breast tissues. Through a comparison with corresponding histology and OCT images, OCME is shown to enable ready visualization of features such as ducts, lobules, microcysts, blood vessels, and arterioles and to identify invasive tumor through distinctive patterns in OCME images, often with enhanced contrast compared with OCT. These results lay the foundation for future intraoperative studies. Cancer Res; 75(16); 3236–45. ©2015 AACR.
Antiangiogenic VEGF-Ax: A New Participant in Tumor Angiogenesis
Authors: Eswarappa Sandeepa M. , Fox Paul L. 
Published: June 2015

Abstract
The transcript of the angiogenic factor vascular endothelial growth factor A (VEGF-A) is subject to a multitude of stimulus-dependent, posttranscriptional regulatory events, consistent with its unusually long 3′ untranslated region. We have recently reported translational readthrough of VEGFA mRNA whereby translating ribosomes traverse the canonical stop codon to a conserved, downstream stop codon, generating VEGF-Ax (“x” for extended), a novel, extended isoform with an additional 22 amino acids appended at the C-terminus. This event is the first vertebrate example of protein-regulated, programmed translational readthrough that generates a protein with a known function. Remarkably, VEGF-Ax exhibits potent antiangiogenic activity, both in vitro and in vivo, thus raising profound clinical implications, particularly with respect to cancer treatment. In this review, we discuss the potential of VEGF-Ax as a therapeutic agent and drug target, as well as its possible role in the failure of, or resistance to, conventional anti-VEGF therapies in many types of cancers. Cancer Res; 75(14); 2765–9. ©2015 AACR.