bluuebunny/crossref_metadata_2025_split huggingface dataset:
NDM-5 Carbapenemase-Encoding Gene in Multidrug-Resistant Clinical Isolates of Escherichia coli from Algeria
Authors: Sassi Asma , Loucif Lotfi , Gupta Sushim Kumar , Dekhil Mazouz , Chettibi Houria , Rolain Jean-Marc 
Published: July 2014

ABSTRACT

Here, we report the first autochthonous cases of infections caused by
bla
NDM-5
New Delhi metallo-β-lactamase-producing
Escherichia coli
strains recovered from urine and blood specimens of three patients from Algeria between January 2012 and February 2013. The three isolates belong to sequence type 2659 and they coexpress
bla
CTX-M-15
with the
bla
TEM-1
and
bla
aadA2
genes.
In Vitro
and
In Vivo
Activities of Antimicrobial Peptides Developed Using an Amino Acid-Based Activity Prediction Method
Authors: Wu Xiaozhe , Wang Zhenling , Li Xiaolu , Fan Yingzi , He Gu , Wan Yang , Yu Chaoheng , Tang Jianying , Li Meng , Zhang Xian , Zhang Hailong , Xiang Rong , Pan Ying , Liu Yan , Lu Lian , Yang Li 
Published: July 2014

ABSTRACT

To design and discover new antimicrobial peptides (AMPs) with high levels of antimicrobial activity, a number of machine-learning methods and prediction methods have been developed. Here, we present a new prediction method that can identify novel AMPs that are highly similar in sequence to known peptides but offer improved antimicrobial activity along with lower host cytotoxicity. Using previously generated AMP amino acid substitution data, we developed an amino acid activity contribution matrix that contained an activity contribution value for each amino acid in each position of the model peptide. A series of AMPs were designed with this method. After evaluating the antimicrobial activities of these novel AMPs against both Gram-positive and Gram-negative bacterial strains, DP7 was chosen for further analysis. Compared to the parent peptide HH2, this novel AMP showed broad-spectrum, improved antimicrobial activity, and in a cytotoxicity assay it showed lower toxicity against human cells. The
in vivo
antimicrobial activity of DP7 was tested in a
Staphylococcus aureus
infection murine model. When inoculated and treated via intraperitoneal injection, DP7 reduced the bacterial load in the peritoneal lavage solution. Electron microscope imaging and the results indicated disruption of the
S. aureus
outer membrane by DP7. Our new prediction method can therefore be employed to identify AMPs possessing minor amino acid differences with improved antimicrobial activities, potentially increasing the therapeutic agents available to combat multidrug-resistant infections.
In Vitro
Activities of Nine Antifungal Drugs and Their Combinations against Phialophora verrucosa
Authors: Li Yali , Wan Zhe , Li Ruoyu 
Published: July 2014

ABSTRACT

The
in vitro
activities of nine antifungal drugs and their combinations against 31 clinical and 15 environmental
Phialophora verrucosa
strains were tested. The MIC
90
/90% minimum effective concentration (MIC/MEC
90
) values (μg/ml) across all strains were as follows: for terbinafine, 0.25; for posaconazole, 0.5; for voriconazole, 1; for itraconazole, 2; for amphotericin B, 4; for caspofungin and micafungin, 16; and for fluconazole and flucytosine, 64. The highest synergy was shown by the combination of itraconazole plus caspofungin (with synergy against 100% of the 31 clinical strains), followed by amphotericin B plus flucytosine (45.2%) and itraconazole plus terbinafine or micafungin (25.8% or 12.9%, respectively).
In Vitro
Antifungal Susceptibility Profile and Correlation of Mycelial and Yeast Forms of Molecularly Characterized Histoplasma capsulatum Strains from India
Authors: Kathuria Shallu , Singh Pradeep K. , Meis Jacques F. , Chowdhary Anuradha 
Published: July 2014

ABSTRACT

The antifungal susceptibility profiles of the mycelial and yeast forms of 23
Histoplasma capsulatum
strains from pulmonary and disseminated histoplasmosis patients in India are reported here. The MIC data of this dimorphic fungus had good agreement between both forms for azoles, amphotericin B, and caspofungin. Therefore, the use of mycelial inocula for
H. capsulatum
antifungal susceptibility testing is suggested, which is less time-consuming vis-à-vis the yeast form, which requires 6 to 8 weeks for conversion.
Emergence of Multidrug-Resistant Campylobacter Species Isolates with a Horizontally Acquired rRNA Methylase
Authors: Wang Yang , Zhang Maojun , Deng Fengru , Shen Zhangqi , Wu Congming , Zhang Jianzhong , Zhang Qijing , Shen Jianzhong 
Published: July 2014

ABSTRACTAntibiotic-resistantCampylobacterconstitutes a serious threat to public health, and resistance to macrolides is of particular concern, as this class of antibiotics is the drug of choice for clinical therapy of campylobacteriosis. Very recently, a horizontally transferrable macrolide resistance mediated by the rRNA methylase geneerm(B) was reported in aCampylobacter coliisolate, but little is known about the dissemination oferm(B) amongCampylobacterisolates and the association oferm(B)-carrying isolates with clinical disease. To address this question and facilitate the control of antibiotic-resistantCampylobacter, we determined the distribution oferm(B) in 1,554C. coliandCampylobacter jejuniisolates derived from food-producing animals and clinically confirmed human diarrheal cases. The results revealed that 58 of the examined isolates harborederm(B) and exhibited high-level resistance to macrolides, and most were recent isolates, derived in 2011-2012. In addition, theerm(B)-positive isolates were all resistant to fluoroquinolones, another clinically important antibiotic used for treating campylobacteriosis. Theerm(B) gene is found to be associated with chromosomal multidrug resistance genomic islands (MDRGIs) of Gram-positive origin or with plasmids of various sizes. All MDRGIs were transferrable to macrolide-susceptibleC. jejuniby natural transformation under laboratory conditions. Molecular typing of theerm(B)-carrying isolates by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) identified diverse genotypes and outbreak-associated diarrheal isolates. Molecular typing also suggested zoonotic transmission oferm(B)-positiveCampylobacter. These findings reveal an emerging and alarming trend of dissemination oferm(B) and MDRGIs inCampylobacterand underscore the need for heightened efforts to control their further spread.
Genotypic and Phenotypic Analyses of Hepatitis C Virus Variants Observed in Clinical Studies of VX-222, a Nonnucleoside NS5B Polymerase Inhibitor
Authors: Jiang Min , Zhang Eileen Z. , Ardzinski Andrzej , Tigges Ann , Davis Andrew , Sullivan James C. , Nelson Michelle , Spanks Joan , Dorrian Jennifer , Nicolas Olivier , Bartels Doug J. , Rao B. Govinda , Rijnbrand Rene , Kieffer Tara L. 
Published: July 2014

ABSTRACT

VX-222, a thiophene-2-carboxylic acid derivative, is a selective nonnucleoside inhibitor of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. In phase 1 and 2 clinical studies, VX-222 demonstrated effective antiviral efficacy, with substantial reductions in plasma HCV RNA in patients chronically infected with genotype 1 HCV. To characterize the potential for selection of VX-222-resistant variants in HCV-infected patients, the HCV NS5B gene was sequenced at baseline and during and after 3 days of VX-222 dosing (monotherapy) in a phase 1 study. Variants with the substitutions L419C/I/M/P/S/V, R422K, M423I/T/V, I482L/N/T, A486S/T/V, and V494A were selected during VX-222 dosing, and their levels declined over time after the end of dosing. Phenotypic analysis of these variants was conducted using HCV replicons carrying site-directed mutations. Of the 17 variants, 14 showed reduced susceptibility to VX-222 compared with the wild type, with the L419C/S and R422K variants having higher levels of resistance (>200-fold) than the rest of the variants (6.8- to 76-fold). The M423I and A486S variants remained susceptible to VX-222. The 50% effective concentration (EC
50
) for the L419P variant could not be obtained due to the poor replication of this replicon. The majority of the variants (15/17) were less fit than the wild type. A subset of the variants, predominately the L419S and R422K variants, were observed when the efficacy and safety of VX-222- and telaprevir-based regimens given for 12 weeks were investigated in genotype 1 HCV-infected patients in a phase 2 study. The NS3 and NS5B variants selected during the dual combination therapy showed reduced susceptibility to both telaprevir and VX-222 and had a lower replication capacity than the wild type. The phase 1b study has the ClinicalTrials.gov identifier NCT00911963, and the phase 2a study has ClinicalTrials.gov identifier NCT01080222.
Quasi-Experimental Study of Sodium Citrate Locks and the Risk of Acute Hemodialysis Catheter Infection among Critically Ill Patients
Authors: Parienti Jean-Jacques , Deryckère Stéphanie , Mégarbane Bruno , Valette Xavier , Seguin Amélie , Sauneuf Bertrand , Mira Jean-Paul , Souweine Bertrand , Cattoir Vincent , Daubin Cédric , du Cheyron Damien 
Published: July 2014

ABSTRACT

Critically ill patients who require renal replacement therapy (RRT) are vulnerable to catheter-related bloodstream infections (CRBSI). This study compared the risks of dialysis catheter infection according to the choice of locking solution in the intensive care unit (ICU). A prospective quasi-experimental study with marginal structural models (MSM) and 2:1 greedy propensity-score matching (PSM) was conducted at nine university-affiliated hospitals and three general hospitals. A total of 596 critically ill patients received either saline solution or heparin lock solution (the standard of care [SOC]) from 2004 to 2007 in the Cathedia cohort (
n
= 464 for MSM;
n
= 124 for PSM) or 46.7% citrate lock from 2011 to 2012 in the citrate (CLock) cohort (
n
= 132 for MSM;
n
= 62 for PSM) to perform RRT using intermittent hemodialysis. Catheter-tip colonization and CRBSI were analyzed. The mean duration (standard deviation [SD]) of catheterization was 7.1 days (6.1) in the SOC group and 7.0 days (5.9) in the CLock group (
P
= 0.84). The risk of dialysis catheter-tip colonization was lower in the CLock group (20.5 versus 38.7 per 1,000 catheter-days in the SOC group; hazard ratio [HR] from MSM, 0.73; 95% confidence interval [CI], 0.57 to 0.93;
P
< 0.02). Consistent findings were found from PSM (HR, 0.46; 95% CI, 0.22 to 0.95;
P
< 0.04). The risk of CRBSI was nonsignificantly different in the CLock group (1.1 versus 1.8 per 1,000 catheter-days in the SOC group; HR from MSM, 0.48; 95% CI, 0.12 to 1.87;
P
= 0.29). By reducing the risk of catheter-tip colonization, citrate lock has the potential to improve hemodialysis safety in the ICU. Additional studies are warranted before the routine use of citrate locks can be recommended in the ICU.
A Broad-Spectrum Antibiofilm Peptide Enhances Antibiotic Action against Bacterial Biofilms
Authors: Reffuveille Fany , de la Fuente-Núñez César , Mansour Sarah , Hancock Robert E. W. 
Published: July 2014

ABSTRACT

Biofilm-related infections account for at least 65% of all human infections, but there are no available antimicrobials that specifically target biofilms. Their elimination by available treatments is inefficient since biofilm cells are between 10- and 1,000-fold more resistant to conventional antibiotics than planktonic cells. Here we describe the synergistic interactions, with different classes of antibiotics, of a recently characterized antibiofilm peptide, 1018, to potently prevent and eradicate bacterial biofilms formed by multidrug-resistant ESKAPE (
Enterococcus faecium
,
Staphylococcus aureus
,
Klebsiella pneumoniae
,
Acinetobacter baumannii
,
Pseudomonas aeruginosa
, and
Enterobacter
species) pathogens. Combinations of peptide 1018 and the antibiotic ceftazidime, ciprofloxacin, imipenem, or tobramycin were synergistic in 50% of assessments and decreased by 2- to 64-fold the concentration of antibiotic required to treat biofilms formed by
Pseudomonas aeruginosa
,
Escherichia coli
,
Acinetobacter baumannii
,
Klebsiella pneumoniae
,
Salmonella enterica
, and methicillin-resistant
Staphylococcus aureus
. Furthermore, in flow cell biofilm studies, combinations of low, subinhibitory levels of the peptide (0.8 μg/ml) and ciprofloxacin (40 ng/ml) decreased dispersal and triggered cell death in mature
P. aeruginosa
biofilms. In addition, short-term treatments with the peptide in combination with ciprofloxacin prevented biofilm formation and reduced
P. aeruginosa
PA14 preexisting biofilms. PCR studies indicated that the peptide suppressed the expression of various antibiotic targets in biofilm cells. Thus, treatment with the peptide represents a novel strategy to potentiate antibiotic activity against biofilms formed by multidrug-resistant pathogens.
Bacterial Siderophores That Evade or Overwhelm Lipocalin 2 Induce Hypoxia Inducible Factor 1α and Proinflammatory Cytokine Secretion in Cultured Respiratory Epithelial Cells
Authors: Holden Victoria I. , Lenio Steven , Kuick Rork , Ramakrishnan Sadeesh K. , Shah Yatrik M. , Bachman Michael A. 
Published: July 2014

ABSTRACT
Iron is essential for many cellular processes and is required by bacteria for replication. To acquire iron from the host, pathogenic Gram-negative bacteria secrete siderophores, including enterobactin (Ent). However, Ent is bound by the host protein lipocalin 2 (Lcn2), preventing bacterial reuptake of aferric or ferric Ent. Furthermore, the combination of Ent and Lcn2 (Ent+Lcn2) leads to enhanced secretion of interleukin-8 (IL-8) compared to that induced by either stimulus alone. Modified or structurally distinct siderophores, including yersiniabactin (Ybt) and glycosylated Ent (GlyEnt, or salmochelin), deliver iron to bacteria despite the presence of Lcn2. We hypothesized that the robust immune response to Ent and Lcn2 requires iron chelation rather than the Ent+Lcn2 complex itself and also can be stimulated by Lcn2-evasive siderophores. To test this hypothesis, cultured respiratory epithelial cells were stimulated with combinations of purified siderophores and Lcn2 and analyzed by gene expression microarrays, quantitative PCR, and cytokine immunoassays. Ent caused HIF-1α protein stabilization, induced the expression of genes regulated by hypoxia-inducible factor 1α (HIF-1α), and repressed genes involved in cell cycle and DNA replication, whereas Lcn2 induced expression of proinflammatory cytokines. Iron chelation by excess Ent or Ybt significantly increased Lcn2-induced secretion of IL-8, IL-6, and CCL20. Stabilization of HIF-1α was sufficient to enhance Lcn2-induced IL-6 secretion. These data indicate that respiratory epithelial cells can respond to bacterial siderophores that evade or overwhelm Lcn2 binding by increasing proinflammatory cytokine production.
Evidence that Intraspecific Trait Variation among Nasal Bacteria Shapes the Distribution of Staphylococcus aureus
Authors: Libberton Ben , Coates Rosanna E. , Brockhurst Michael A. , Horsburgh Malcolm J. 
Published: July 2014

ABSTRACT

Nasal carriage of
Staphylococcus aureus
is a risk factor for infection, yet the bacterial determinants required for carriage are poorly defined. Interactions between
S. aureus
and other members of the bacterial flora may determine colonization and have been inferred in previous studies by using correlated species distributions. However, traits mediating species interactions are often polymorphic, suggesting that understanding how interactions structure communities requires a trait-based approach. We characterized
S. aureus
growth inhibition by the culturable bacterial aerobe consortia of 60 nasal microbiomes, and this revealed intraspecific variation in growth inhibition and that inhibitory isolates clustered within communities that were culture negative for
S. aureus
. Across microbiomes, the cumulative community-level growth inhibition was negatively associated with
S. aureus
incidence. To fully understand the ecological processes structuring microbiomes, it will be crucial to account for intraspecific variation in the traits that mediate species interactions.
Genome-Wide Analysis of the Role of Global Transcriptional Regulator GntR1 in Corynebacterium glutamicum
Authors: Tanaka Yuya , Takemoto Norihiko , Ito Terukazu , Teramoto Haruhiko , Yukawa Hideaki , Inui Masayuki 
Published: July 2014

ABSTRACT

The transcriptional regulator GntR1 downregulates the genes for gluconate catabolism and pentose phosphate pathway in
Corynebacterium glutamicum
. Gluconate lowers the DNA binding affinity of GntR1, which is probably the mechanism of gluconate-dependent induction of these genes. In addition, GntR1 positively regulates
ptsG
, a gene encoding a major glucose transporter, and
pck
, a gene encoding phosphoenolpyruvate carboxykinase. Here, we searched for the new target of GntR1 on a genome-wide scale by chromatin immunoprecipitation in conjunction with microarray (ChIP-chip) analysis. This analysis identified 56
in vivo
GntR1 binding sites, of which 7 sites were previously reported. The newly identified GntR1 sites include the upstream regions of carbon metabolism genes such as
pyk
,
maeB
,
gapB
, and
icd
, encoding pyruvate kinase, malic enzyme, glyceraldehyde 3-phosphate dehydrogenase B, and isocitrate dehydrogenase, respectively. Binding of GntR1 to the promoter region of these genes was confirmed by electrophoretic mobility shift assay. The activity of the
icd
,
gapB
, and
maeB
promoters was reduced by the mutation at the GntR1 binding site, in contrast to the
pyk
promoter activity, which was increased, indicating that GntR1 is a transcriptional activator of
icd
,
gapB
, and
maeB
and is a repressor of
pyk
. Thus, it is likely that GntR1 stimulates glucose uptake by inducing the phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS) gene while repressing
pyk
to increase PEP availability in the absence of gluconate. Repression of
zwf
and
gnd
may reduce the NADPH supply, which may be compensated by the induction of
maeB
and
icd
. Upregulation of
icd
,
gapB
, and
maeB
and downregulation of
pyk
by GntR1 probably support gluconeogenesis.
Implementation of clinical practices to reduce return visits within 72 h to a paediatric emergency department
Authors: Jeong Jin Hee , Hwang Seung Sik , Kim Kyuseok , Lee Jin Hee , Rhee Joong Eui , Kang Changwoo , Lee Soo Hoon , Kim Hooyoung , Im Yeon Sook , Lee Boeknam , Byeon Young Im , Lee Ji Sook 
Published: July 2014

ObjectiveReturn visits to the paediatric emergency department (PED) are an important measure of quality of healthcare and are associated with patients’ and parents’/guardians’ satisfaction. Previous studies have been limited to describing characteristics and factors related to return visits. The objectives of this study were to develop new clinical practices to reduce return visits to the PED and to see whether implementation of these practices had the desired effect.Patients and methodsThis was a controlled before-and-after study. New clinical practices were developed by analysing data for patients visiting in 2011 (before) and by surveying emergency physicians and nurses in the PED. New clinical practices were implemented between 16 July and 4 November 2012 (after). The rate of return visits and admission rates after return visits were compared between matched periods in 2011 and 2012. We also investigated return visits at three independent hospitals to overcome the limitation of the intervention application to a single hospital.ResultsThe new clinical practices included five protocols: set orders for common symptoms; management plans for patients at high risk of a return visit; a daily physician feedback system; protocolised discharge instructions; early planned visits to clinics. After implementation, the rate of return visits was reduced significantly, from 4.4% to 2.6% (p<0.01). The admission rate for return visits was also reduced, but not significantly so, from 22.3% to 17.5% (p=0.37). Return visits at the other hospitals were similar or significantly increased in 2012 compared with 2011.ConclusionsThe development and implementation of clinical practices were effective in reducing return visits of paediatric patients to the ED.
New Barrett's oesophagus surveillance guidelines: significant cost savings over the next 10 years on implementation
Authors: Hewett Rhys , Chan Derek , Kang Jin-Yong , Poullis Andrew 
Published: July 2014

ObjectiveWe aimed to estimate the cost saving (over the next 10 years) by our trust implementing the new British Society of Gastroenterology (BSG) surveillance guidelines for Barrett's oesophagus (BO).DesignRetrospective endoscopy database analysis.SettingTwo endoscopy units of St George's Hospital NHS Trust, London.PatientsGastroscopy records between 2009 and 2012 were retrieved and patients with an endoscopic diagnosis of BO were identified. BO segment length was recorded and the presence (or absence) of intestinal metaplasia in the oesophageal biopsy samples was reviewed from pathology databases. Patients were then stratified into risk groups in accordance with the new BSG guidelines.InterventionsNil.Main outcome measuresThe projected surveillance costs using the new and the old guidelines were calculated over the next 10 years and the cost saving by the implementation of the new guidelines thus determined.ResultsThe 10 year projected cost saving for our trust by implementing the new BO surveillance guidelines was £720 330 (or £72 033 per annum). Projected across the NHS, implementation of the new guidance may save £100 million over the next 10 years.ConclusionsAll trusts should review their Barrett's surveillance population and implement these new recommendations expeditiously.
FPGA Implementation of a Special-Purpose VLIW Structure for Double-Precision Elementary Function
Authors: Lei Yuanwu , Guo Lei , Dou Yong , Ma Sheng , Xu Jinbo 
Published: July 2014

In the current article, the capability and flexibility of field programmable gate-arrays (FPGAs) to implement IEEE-754 double-precision floating-point elementary functions are explored. To perform various elementary functions on the unified hardware efficiently, we propose a special-purpose very long instruction word (VLIW) processor, called DP_VELP. This processor is equipped with multiple basic units, and its performance is improved through an explicitly parallel technique. Pipelined evaluation of polynomial approximation with Estrin's scheme is proposed, by scheduling basic components in an optimal order to avoid data hazard stalls and achieve minimal latency. The custom VLIW processor can achieve high scalability. Under the control of specific VLIW instructions, the basic units are combined into special-purpose hardware for elementary functions. Common elementary functions are presented as examples to illustrate the design of elementary function in DP_VELP in detail. Minimax approximation scheme is used to reduce degree of polynomial. Compromise between the size of lookup table and the latency is discussed, and the internal precision is carefully planned to guarantee accuracy of the result. Finally, we create a prototype of the DP_VELP unit and an FPGA accelerator based on the DP_VELP unit on a Xilinx XC6VLX760 FPGA chip to implement the SGP4/SDP4 application.
Compared with previous researches, the proposed design can achieve low latency with a reasonable amount of resources and evaluate a variety of elementary functions with the unified hardware to satisfy the demands in scientific applications. Experimental results show that the proposed design guarantees more than 99% of correct rounding. Moreover, the SGP4/SDP4 accelerator, which is equipped with 39 DP_VELP units and runs at 200 MHz, outperforms the parallel software approach with hyper-thread technology on an Intel Xeon Quad E5620 CPU at 2.40 GHz by a factor of 7X.