bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of duct‐to‐duct vs. Roux‐en‐Y hepaticojejunostomy biliary anastomoses in below 15‐kg pediatric liver transplant recipients
Authors: Shaheen Mohammed F. , Alabdulkarim Moayad S. , Hamshow Mohammad M. , Abdullah Khalid O. , O'Hali Wael A. 
Published: September 2014

AbstractThe best type of biliary anastomosis to use in lower weight pediatric liver transplant recipients is debatable. In this study, we share a single center's experience comparing the rate of anastomotic biliary complications based on the type of biliary anastomosis performed in this population of patients. A retrospective review of pediatric liver transplants for recipients weighing <15 kg from 11/2003 till 12/2011 was performed. Patients were grouped based on the type of biliary anastomosis into two groups: duct‐to‐duct (d‐d) and Roux‐en‐Y hepaticojejunostomy (h‐j) anastomoses. A total of 24 patients (12 males, 12 females) with a mean age of 26 ± 20 months and a mean weight of 9.27 ± 2.63 kg (range = 5.3–13.9 kg) were studied. All anastomotic complications occurred in patients who received left lateral segments. No statistical differences were found in the post‐operative biliary (p = 0.86) or vascular (p = 0.99) complications between the two groups. Acknowledging the limited sample size, our data suggest that duct‐to‐duct anastomosis can be performed safely in pediatric liver transplantation recipients weighing below 15 kg.
Prolonged fever and splenic lesions caused by Malassezia restricta in an immunocompromised patient
Authors: de St Maurice Annabelle , Frangoul Haydar , Coogan Alice , Williams John V. 
Published: September 2014

AbstractMalassezia species are commonly found on human skin as commensals but can cause invasive infections in premature infants and immunocompromised hosts. Due to their fastidious growth, diagnosis of Malassezia infections can prove challenging. Molecular techniques can aid in diagnosis and treatment of invasive infections. We describe the case of a pediatric oncology patient with splenic lesions secondary to Malassezia restricta.
Lariation of Learning Intensity in Late Adolescence and the Effect on Personality Traits
Authors: Thiel Hendrik , Thomsen Stephan L. , Büttner Bettina 
Published: September 2014

SummaryEmpirical studies have shown plasticity of personality traits until early adulthood. The extent to which schooling is a crucial determinant in this context has not yet been analysed coherently. Although they have left the curriculum largely unchanged, most German states have abolished the final year of higher secondary schooling to enable earlier graduation. We use this exogenous shift in policy in one German federal state to evaluate the effects of an increase in the amount of curriculum per unit of time on different personality traits. The results indicate that the development of personality does not depend on schooling characteristics at that particular age.
Disruption of the Transcriptional Regulator Cas5 Results in Enhanced Killing of Candida albicans by Fluconazole
Authors: Vasicek Erin M. , Berkow Elizabeth L. , Bruno Vincent M. , Mitchell Aaron P. , Wiederhold Nathan P. , Barker Katherine S. , Rogers P. David 
Published: September 2014

ABSTRACT

Azole antifungal agents such as fluconazole exhibit fungistatic activity against
Candida albicans
. Strategies to enhance azole antifungal activity would be therapeutically appealing. In an effort to identify transcriptional pathways that influence the killing activity of fluconazole, we sought to identify transcription factors (TFs) involved in this process. From a collection of
C. albicans
strains disrupted for genes encoding TFs (O. R. Homann, J. Dea, S. M. Noble, and A. D. Johnson, PLoS Genet. 5:e1000783, 2009,
http://dx.doi.org/10.1371/journal.pgen.1000783
), four strains exhibited marked reductions in minimum fungicidal concentration (MFCs) in both RPMI and yeast extract-peptone-dextrose (YPD) media. One of these genes,
UPC2
, was previously characterized with regard to its role in azole susceptibility. Of mutants representing the three remaining TF genes of interest, one (
CAS5
) was unable to recover from fluconazole exposure at concentrations as low as 2 μg/ml after 72 h in YPD medium. This mutant also showed reduced susceptibility and a clear zone of inhibition by Etest, was unable to grow on solid medium containing 10 μg/ml fluconazole, and exhibited increased susceptibility by time-kill analysis.
CAS5
disruption in highly azole-resistant clinical isolates exhibiting multiple resistance mechanisms did not alter susceptibility. However,
CAS5
disruption in strains with specific resistance mutations resulted in moderate reductions in MICs and MFCs. Genome-wide transcriptional analysis was performed in the presence of fluconazole and was consistent with the suggested role of
CAS5
in cell wall organization while also suggesting a role in iron transport and homeostasis. These findings suggest that Cas5 regulates a transcriptional network that influences the response of
C. albicans
to fluconazole. Further delineation of this transcriptional network may identify targets for potential cotherapeutic strategies to enhance the activity of the azole class of antifungals.
Complete Sequence of a Conjugative IncN Plasmid Harboring
bla
KPC-2
,
bla
SHV-12
, and
qnrS1
from an Escherichia coli Sequence Type 648 Strain
Authors: Li Jun-Jie , Lee Chang-Seop , Sheng Ji-Fang , Doi Yohei 
Published: September 2014

ABSTRACT

We sequenced a novel conjugative
bla
KPC-2
-harboring IncN plasmid, pYD626E, from an
Escherichia coli
sequence type 648 strain previously identified in Pittsburgh, Pennsylvania. pYD626E was 72,800 bp long and carried four β-lactamase genes,
bla
KPC-2
,
bla
SHV-12
,
bla
LAP-1
, and
bla
TEM-1
. In addition, it harbored
qnrS1
(fluoroquinolone resistance) and
dfrA14
(trimethoprim resistance). The plasmid profile and clinical history supported the
in vivo
transfer of this plasmid between
Klebsiella pneumoniae
and
Escherichia coli
.
Antibacterial Synergy of Glycerol Monolaurate and Aminoglycosides in Staphylococcus aureus Biofilms
Authors: Hess Donavon J. , Henry-Stanley Michelle J. , Wells Carol L. 
Published: September 2014

ABSTRACT

Glycerol monolaurate (GML) is a natural surfactant with antimicrobial properties. At ∼0.3 mM, both GML and its component lauric acid were bactericidal for antibiotic-resistant
Staphylococcus aureus
biofilms. With the use of MICs of antibiotics obtained from planktonic cells, GML and lauric acid acted synergistically with gentamicin and streptomycin, but not ampicillin or vancomycin, to eliminate detectable viable biofilm bacteria. Images of GML-treated biofilms suggested that GML may facilitate antibiotic interaction with matrix-embedded bacteria.
Two-Component System VicRK Regulates Functions Associated with Establishment of Streptococcus sanguinis in Biofilms
Authors: Moraes Julianna J. , Stipp Rafael N. , Harth-Chu Erika N. , Camargo Tarsila M. , Höfling José F. , Mattos-Graner Renata O. 
Published: September 2014

ABSTRACT

Streptococcus sanguinis
is a commensal pioneer colonizer of teeth and an opportunistic pathogen of infectious endocarditis. The establishment of
S. sanguinis
in host sites likely requires dynamic fitting of the cell wall in response to local stimuli. In this study, we investigated the two-component system (TCS) VicRK in
S. sanguinis
(VicRK

Ss

), which regulates genes of cell wall biogenesis, biofilm formation, and virulence in opportunistic pathogens. A
vicK
knockout mutant obtained from strain SK36 (SKvic) showed slight reductions in aerobic growth and resistance to oxidative stress but an impaired ability to form biofilms, a phenotype restored in the complemented mutant. The biofilm-defective phenotype was associated with reduced amounts of extracellular DNA during aerobic growth, with reduced production of H
2
O
2
, a metabolic product associated with DNA release, and with inhibitory capacity of
S. sanguinis
competitor species. No changes in autolysis or cell surface hydrophobicity were detected in SKvic. Reverse transcription-quantitative PCR (RT-qPCR), electrophoretic mobility shift assays (EMSA), and promoter sequence analyses revealed that VicR directly regulates genes encoding murein hydrolases (
SSA_0094
,
cwdP
, and
gbpB
) and
spxB
, which encodes pyruvate oxidase for H
2
O
2
production. Genes previously associated with
spxB
expression (
spxR
,
ccpA
,
ackA
, and
tpK
) were not transcriptionally affected in SKvic. RT-qPCR analyses of
S. sanguinis
biofilm cells further showed upregulation of VicRK targets (
spxB
,
gbpB
, and
SSA_0094
) and other genes for biofilm formation (
gtfP
and
comE
) compared to expression in planktonic cells. This study provides evidence that VicRK

Ss

regulates functions crucial for
S. sanguinis
establishment in biofilms and identifies novel VicRK targets potentially involved in hydrolytic activities of the cell wall required for these functions.
Vaccine Protection of Leukopenic Mice against Staphylococcus aureus Bloodstream Infection
Authors: Rauch Sabine , Gough Portia , Kim Hwan Keun , Schneewind Olaf , Missiakas Dominique 
Published: September 2014

ABSTRACT

The risk for
Staphylococcus aureus
bloodstream infection (BSI) is increased in immunocompromised individuals, including patients with hematologic malignancy and/or chemotherapy. Due to the emergence of antibiotic-resistant strains, designated methicillin-resistant
S. aureus
(MRSA), staphylococcal BSI in cancer patients is associated with high mortality; however, neither a protective vaccine nor pathogen-specific immunotherapy is currently available. Here, we modeled staphylococcal BSI in leukopenic CD-1 mice that had been treated with cyclophosphamide, a drug for leukemia and lymphoma patients. Cyclophosphamide-treated mice were highly sensitive to
S. aureus
BSI and developed infectious lesions lacking immune cell infiltrates. Virulence factors of
S. aureus
that are key for disease establishment in immunocompetent hosts—α-hemolysin (Hla), iron-regulated surface determinants (IsdA and IsdB), coagulase (Coa), and von Willebrand factor binding protein (vWbp)—are dispensable for the pathogenesis of BSI in leukopenic mice. In contrast, sortase A mutants, which cannot assemble surface proteins, display delayed time to death and increased survival in this model. A vaccine with four surface antigens (ClfA, FnBPB, SdrD, and SpA
KKAA
), which was identified by genetic vaccinology using sortase A mutants, raised antigen-specific immune responses that protected leukopenic mice against staphylococcal BSI.
Molecular Characterization of Protease Activity in Serratia sp. Strain SCBI and Its Importance in Cytotoxicity and Virulence
Authors: Petersen Lauren M. , Tisa Louis S. 
Published: September 2014

ABSTRACT

A newly recognized
Serratia
species, termed South African
Caenorhabditis briggsae
isolate (SCBI), is both a mutualist of the nematode
Caenorhabditis briggsae
KT0001 and a pathogen of lepidopteran insects.
Serratia
sp. strain SCBI displays high proteolytic activity, and because secreted proteases are known virulence factors for many pathogens, the purpose of this study was to identify genes essential for extracellular protease activity in
Serratia
sp. strain SCBI and to determine what role proteases play in insect pathogenesis and cytotoxicity. A bank of 2,100 transposon mutants was generated, and six SCBI mutants with defective proteolytic activity were identified. These mutants were also defective in cytotoxicity. The mutants were found defective in genes encoding the following proteins: alkaline metalloprotease secretion protein AprE, a BglB family transcriptional antiterminator, an inosine/xanthosine triphosphatase, GidA, a methyl-accepting chemotaxis protein, and a PIN domain protein. Gene expression analysis on these six mutants showed significant downregulation in mRNA levels of several different types of predicted protease genes. In addition, transcriptome sequencing (RNA-seq) analysis provided insight into how inactivation of AprE, GidA, and a PIN domain protein influences motility and virulence, as well as protease activity. Using quantitative reverse transcription-PCR (qRT-PCR) to further characterize expression of predicted protease genes in wild-type
Serratia
sp. SCBI, the highest mRNA levels for the alkaline metalloprotease genes (termed
prtA1
to
prtA4
) occurred following the death of an insect host, while two serine protease and two metalloprotease genes had their highest mRNA levels during active infection. Overall, these results indicate that proteolytic activity is essential for cytotoxicity in
Serratia
sp. SCBI and that its regulation appears to be highly complex.
The TetR-Type MfsR Protein of the Integrative and Conjugative Element (ICE) ICE
clc
Controls both a Putative Efflux System and Initiation of ICE Transfer
Authors: Pradervand Nicolas , Delavat François , Sulser Sandra , Miyazaki Ryo , van der Meer Jan Roelof 
Published: September 2014

ABSTRACT

Integrative and conjugating elements (ICE) are self-transferable DNAs widely present in bacterial genomes, which often carry a variety of auxiliary genes of potential adaptive benefit. One of the model ICE is ICE
clc
, an element originally found in
Pseudomonas knackmussii
B13 and known for its propensity to provide its host with the capacity to metabolize chlorocatechols and 2-aminophenol. In this work, we studied the mechanism and target of regulation of MfsR, a TetR-type repressor previously found to exert global control on ICE
clc
horizontal transfer. By using a combination of ICE
clc
mutant and transcriptome analysis, gene reporter fusions, and DNA binding assays, we found that MfsR is a repressor of both its own expression and that of a gene cluster putatively coding for a major facilitator superfamily efflux system on ICE
clc
(named
mfsABC
). Phylogenetic analysis suggests that
mfsR
was originally located immediately adjacent to the efflux pump genes but became displaced from its original
cis
target DNA by a gene insertion. This resulted in divergence of the original bidirectional promoters into two separated individual regulatory units. Deletion of
mfsABC
did not result in a strong phenotype, and despite screening a large number of compounds and conditions, we were unable to define the precise current function or target of the putative efflux pump. Our data reconstruct how the separation of an ancestor
mfsR-mfsABC
system led to global control of ICE
clc
transfer by MfsR.
Transcriptional Analysis of the Global Regulatory Networks Active in Pseudomonas syringae during Leaf Colonization
Authors: Yu Xilan , Lund Steven P. , Greenwald Jessica W. , Records Angela H. , Scott Russell A. , Nettleton Dan , Lindow Steven E. , Gross Dennis C. , Beattie Gwyn A. 
Published: September 2014

ABSTRACT

The plant pathogen
Pseudomonas syringae
pv. syringae B728a grows and survives on leaf surfaces and in the leaf apoplast of its host, bean (
Phaseolus vulgaris
). To understand the contribution of distinct regulators to B728a fitness and pathogenicity, we performed a transcriptome analysis of strain B728a and nine regulatory mutants recovered from the surfaces and interior of leaves and exposed to environmental stresses in culture. The quorum-sensing regulators AhlR and AefR influenced few genes
in planta
or
in vitro
. In contrast, GacS and a downstream regulator, SalA, formed a large regulatory network that included a branch that regulated diverse traits and was independent of plant-specific environmental signals and a plant signal-dependent branch that positively regulated secondary metabolite genes and negatively regulated the type III secretion system. SalA functioned as a central regulator of iron status based on its reciprocal regulation of pyoverdine and achromobactin genes and also sulfur uptake, suggesting a role in the iron-sulfur balance. RetS functioned almost exclusively to repress secondary metabolite genes when the cells were not on leaves. Among the sigma factors examined, AlgU influenced many more genes than RpoS, and most AlgU-regulated genes depended on RpoN. RpoN differentially impacted many AlgU- and GacS-activated genes in cells recovered from apoplastic versus epiphytic sites, suggesting differences in environmental signals or bacterial stress status in these two habitats. Collectively, our findings illustrate a central role for GacS, SalA, RpoN, and AlgU in global regulation in B728a
in planta
and a high level of plasticity in these regulators’ responses to distinct environmental signals.

IMPORTANCE
Leaves harbor abundant microorganisms, all of which must withstand challenges such as active plant defenses and a highly dynamic environment. Some of these microbes can influence plant health. Despite knowledge of individual regulators that affect the fitness or pathogenicity of foliar pathogens, our understanding of the relative importance of various global regulators to leaf colonization is limited.
Pseudomonas syringae
strain B728a is a plant pathogen and a good colonist of both the surfaces and interior of leaves. This study used global transcript profiles of strain B728a to investigate the complex regulatory network of putative quorum-sensing regulators, two-component regulators, and sigma factors in cells colonizing the leaf surface and leaf interior under stressful
in vitro
conditions. The results highlighted the value of evaluating these networks
in planta
due to the impact of leaf-specific environmental signals and suggested signal differences that may enable cells to differentiate surface versus interior leaf habitats.
An audit of anticoagulant management to assess anticoagulant control using decision support software
Authors: Harper Paul , Harper Joe , Hill Claire 
Published: September 2014

ObjectiveTo evaluate the effectiveness of a computerised self-adjusting anticoagulant algorithm to predict appropriate warfarin dosing and to assess its use in clinical practice.DesignA 3-year audit of anticoagulant control in patients managed by doctors and pharmacists using computer decision support and an evaluation of the impact of dose adjustments made by the users.Participants3660 patients on oral anticoagulants; one-third of patients managed by doctors and two-thirds by pharmacists.SettingAnticoagulant supervision in primary care and pharmacies at 60 sites in New Zealand.Main outcome measuresThe time in the therapeutic range (TTR), the outcome of adherence to the computer dosing algorithm, the percentage of time the clinicians over-ride the algorithm and the impact of their intervention on anticoagulant control.ResultsA TTR of 72.9% was achieved for all patients. The TTR was significantly better in patients managed by pharmacists than doctors (75.1% versus 67.4%, p<0.0001). The computer algorithm provides appropriate dose recommendations for INR results from 1.5 to 4. Users administered a dose that differed from the computer recommendation 23.3% of the time. The doctors adjusted the dose more frequently (28.2% versus 21.1% of tests) and made larger dose changes than the pharmacists.ConclusionsThe clinicians predominantly change the dose when the INR is below the therapeutic range. The changes are not necessary to correct for inaccuracies in the algorithm. The most likely explanation is the clinician's belief that their own dose adjustment would achieve better control; however, in practice, their changes tend to underdose patients. The doctors achieved poorer control than the pharmacists; this is in part due to the action of the doctors over-riding the algorithm. Our results imply that clinicians could achieve better anticoagulant control if they more closely followed the computer algorithm.
Compassionate Conversations
Authors: Gardner Sharryn , Bray Dominic 
Published: September 2014

AbstractStaff engagement is much more than just a bonus in any organisation. CQC data shows that it is very clearly linked to positive results in both patient and staff outcomes (fewer complaints, improved safety, reduced sickness, fewer accidents, and more as per Michael West). Staff engagement may seem nebulous but is in fact measured routinely annually in the National Staff Survey. The problem is that often Trust Boards with poor Staff Survey results may struggle to increase staff engagement as staff see management initiatives as 'management fads' or 'tick-box exercises' purely for targets, not their own benefit.Compassionate Conversations are a ground-level initiative focused primarily on supporting and motivating individual staff as the primary focus. This allows the benefits to patients and in Human Resources to be an unspoken anticipated benefit. They are led by a Psychologist and Consultant in a coaching supportive atmosphere in an open or selected group.The Conversations have been rated 9/10 or higher by 64% of participants, while 75% of all participants voluntarily provided feedback. Feedback initially was that Conversations were too clinically-focused and further Conversations were more wide-ranging in topic and included departmental roadshows.
Uniform Exponential Stability of Discrete Evolution Families on Space ofp-Periodic Sequences
Authors: Wang Yongfang , Zada Akbar , Ahmad Nisar , Lassoued Dhaou , Li Tongxing 
Published: August 2014

We prove that the discrete systemζn+1=Anζnis uniformly exponentially stable if and only if the unique solution of the Cauchy problemζn+1=Anζn+eiθn+1zn+1, n∈Z+,ζ0=0,is bounded for any real numberθand anyp-periodic sequencez(n)withz(0)=0. Here,Anis a sequence of bounded linear operators on Banach spaceX.
Molecular Pathways: The PERKs and Pitfalls of Targeting the Unfolded Protein Response in Cancer
Authors: Maas Nancy L. , Diehl J. Alan 
Published: September 2014

Abstract
The endoplasmic reticulum (ER) is a highly specialized organelle that provides an oxidizing, profolding environment for protein synthesis and maturation. The ER also hosts a dynamic signaling network that can sense and respond to physiologic changes that affect its environment, thereby influencing overall cell fate. Limitation of nutrients and oxygen have a direct effect on the efficiency of protein folding in the ER, and are classic inducers of the ER resident signaling pathway, the unfolded protein response (UPR). Not only does the UPR regulate ER homeostasis in normal cells experiencing such stress, but strong evidence also suggests that tumor cells can co-opt the cytoprotective aspects of this response to survive the hypoxic, nutrient-restricted conditions of the tumor microenvironment. Clin Cancer Res; 21(4); 675–9. ©2014 AACR.