bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Left Anterior Line on Left Atrial Appendage Contractility in Patients Who Underwent Catheter Ablation for Chronic Atrial Fibrillation
Authors: JANG SUNG‐WON , OH YONG‐SEOG , SHIN WOO‐SEUNG , UHM JAE SUN , KIM SUNG‐HWAN , KIM JI‐HOON , LEE MAN‐YOUNG , RHO TAI‐HO 
Published: September 2013

BackgroundLeft anterior line (LAL) has been used as a substitute for mitral isthmus line for catheter ablation of chronic atrial fibrillation (AF). However, it results in left anterolateral conduction delay and might affect left atrial (LA) contractility. We aimed to investigate whether LAL decreases LA appendage function.MethodsThis study included 46 patients (30 men, mean age 58 ± 9 years, group 1) with persistent AF who underwent catheter ablation including LAL. Thirty patients with paroxysmal AF who received no additional LA ablation were compared as control group (21 males, mean age 56 ± 8 years, group 2). Transthoracic and transesophageal echocardiography with Doppler tissue imaging was performed in sinus rhythm before and after the ablation. We compared the following variables: (1) E/A ratio of the mitral flow velocity, (2) ratio of early mitral inflow and mitral septal annulus velocity (E/Em), (3) peak velocity of appendage outflow (ApVmax), and (4) time delay from QRS onset to appendage outflow (TDqa).ResultsLA diameter was significantly reduced after ablation in both groups. In group 1, parameters for diastolic function (E/A ratio, 1.7 ± 0.5 vs 2.0 ± 0.6, P = 0.197; E/Em, 11.7 ± 4.8 vs 11.6 ± 5.1, P = 0.883) and appendage flow (ApVmax, 55.2 ± 19.9 cm/s vs 50.3 ± 19.3 cm/s, P = 0.203; TDqa, –77.3 ± 30.1 ms vs –66.1 ± 60.8 ms, P = 0.265) did not change significantly after ablation. Changes of ApVmax and TDqa after ablation were not significantly different between two groups (P = 0.409 and P = 0.195, respectively).ConclusionsLAL ablation did not aggravate mitral flow pattern or change appendage outflow. LAL could be used without concern over worsening LA diastolic and appendage function.
A new ammonoid fauna from the Carnian (Upper Triassic) Kasimlar Formation of the Taurus Mountains (Anatolia, Turkey)
Authors: Lukeneder Susanne , Lukeneder Alexander 
Published: September 2013

AbstractWe describe a new ammonoid fauna from the Taurus Mountains of southern Turkey. The Carnian ammonoid fauna from Aşağiyaylabel is presented for the first time. Ammonoids were obtained from limestone to marl beds of an approximately 35‐m‐thick section, which presents the rare opportunity to investigate ammonoid faunas across the Lower–Upper Carnian boundary. Intense sampling near the village of Aşağiyaylabel led to the recognition of a new Lower Carnian (Julian 2) to Upper Carnian (Tuvalian 1) ammonoid fauna from the Kasimlar Formation. The genus Kasimlarceltites gen. nov. is reported for the first time from the Taurus Mountains, which represents the main faunal element and occurs as huge mass occurrence (n ≫ 1 million). Kasimlarceltites krystyni gen. et sp. nov., Klipsteinia disciformis sp. nov. and Anasirenites crassicrenulatus sp. nov. occur within the Lower Carnian Carbonate member (Units A–B) of the Kasimlar Formation from the Taurus Platform Units. Ammonoids described from the marls of the Tuvalian Marlstone member were deposited during a major, Tethyan‐wide climate crisis – the so‐called Carnian crisis – characterized by a demise of carbonate platforms. Based on the biostratigraphic relevance of certain ammonoid taxa described herein, the age of the analysed parts of the Kasimlar Formation is Julian 2 to Tuvalian 1. The discovery of the new ammonoid assemblages from Aşağiyaylabel substantiates the significance of Upper Triassic faunas within the Taurus Mountains and facilitates the correlation with faunal assemblages from other regions in the Tethyan Realm. The ammonoid fauna and facies indicate a general deepening from open‐platform margins, over deeper shelf settings down to an open marine‐influenced basinal environment. The tentative habitat for Kasimlarceltites gen. nov. is a shallow platform environment to upper mid‐ramp.
Modulation of the autonomic nervous system and behaviour by acute glial cell Gq protein‐coupled receptor activation in vivo
Authors: Agulhon Cendra , Boyt Kristen M. , Xie Alison Xiaoqiao , Friocourt Francois , Roth Bryan L. , McCarthy Ken D. 
Published: September 2013

Key points
The activation of glial Gq protein‐coupled receptor (Gq‐GPCR) signalling cascades broadly activates the autonomic nervous system
The activation of glial Gq‐GPCR signalling cascades affects activity‐related behaviour.
Abstract:  Glial fibrillary acidic protein (GFAP)‐expressing cells (GFAP+ glial cells) are the predominant cell type in the central and peripheral nervous systems. Our understanding of the role of GFAP+ glial cells and their signalling systems in vivo is limited due to our inability to manipulate these cells and their receptors in a cell type‐specific and non‐invasive manner. To circumvent this limitation, we developed a transgenic mouse line (GFAP‐hM3Dq mice) that expresses an engineered Gq protein‐coupled receptor (Gq‐GPCR) known as hM3Dq DREADD (designer receptor exclusively activated by designer drug) selectively in GFAP+ glial cells. The hM3Dq receptor is activated solely by a pharmacologically inert, but bioavailable, ligand (clozapine‐N‐oxide; CNO), while being non‐responsive to endogenous GPCR ligands. In GFAP‐hM3Dq mice, CNO administration increased heart rate, blood pressure and saliva formation, as well as decreased body temperature, parameters that are controlled by the autonomic nervous system (ANS). Additionally, changes in activity‐related behaviour and motor coordination were observed following CNO administration. Genetically blocking inositol 1,4,5‐trisphosphate (IP3)‐dependent Ca2+ increases in astrocytes failed to interfere with CNO‐mediated changes in ANS function, locomotor activity or motor coordination. Our findings reveal an unexpectedly broad role of GFAP+ glial cells in modulating complex physiology and behaviour in vivo and suggest that these effects are not dependent on IP3‐dependent increases in astrocytic Ca2+.
A Novel Methodology for Optimal Design of Compressor Plants Using Probabilistic Plant Design
Authors: Kurz Rainer , Thorp J. Michael , Zentmyer Erik G. , Brun Klaus 
Published: September 2013

Equipment sizing decisions in the oil and gas industry often have to be made based on incomplete data. Often, the exact process conditions are based on numerous assumptions about well performance, market conditions, environmental conditions, and others. Since the ultimate goal is to meet production commitments, the traditional method of addressing this is to use worst case conditions and often adding margins onto these. This will invariably lead to plants that are oversized, in some instances, by large margins. In reality, the operating conditions are very rarely the assumed worst case conditions, however, they are usually more benign most of the time. Plants designed based on worst case conditions, once in operation, will, therefore, usually not operate under optimum conditions, have reduced flexibility, and therefore cause both higher capital and operating expenses.
The authors outline a new probabilistic methodology that provides a framework for more intelligent process-machine designs. A standardized framework using a Monte Carlo simulation and risk analysis is presented that more accurately defines process uncertainty and its impact on machine performance. Case studies are presented that highlight the methodology as applied to critical turbomachinery.
Mechanism of Action of the Novel Aminomethylcycline Antibiotic Omadacycline
Authors: Draper Michael P. , Weir S. , Macone A. , Donatelli J. , Trieber C. A. , Tanaka S. K. , Levy Stuart B. 
Published: September 2013

ABSTRACT

Omadacycline is a novel first-in-class aminomethylcycline with potent activity against important skin and pneumonia pathogens, including community-acquired methicillin-resistant
Staphylococcus aureus
(MRSA), β-hemolytic streptococci, penicillin-resistant
Streptococcus pneumoniae
,
Haemophilus influenzae
, and
Legionella
. In this work, the mechanism of action for omadacycline was further elucidated using a variety of models. Functional assays demonstrated that omadacycline is active against strains expressing the two main forms of tetracycline resistance (efflux and ribosomal protection). Macromolecular synthesis experiments confirmed that the primary effect of omadacycline is on bacterial protein synthesis, inhibiting protein synthesis with a potency greater than that of tetracycline. Biophysical studies with isolated ribosomes confirmed that the binding site for omadacycline is similar to that for tetracycline. In addition, unlike tetracycline, omadacycline is active
in vitro
in the presence of the ribosomal protection protein Tet(O).
In Vivo
Efficacy of Humanized Ceftaroline Fosamil-Avibactam Exposures in a Polymicrobial Infection Model
Authors: Bhalodi Amira A. , Crandon Jared L. , Williams Gregory , Nicolau David P. 
Published: September 2013

ABSTRACT

Although Gram-positive cocci are the most common pathogens in diabetic foot infections, these infections often are polymicrobial. The objective of this study was to assess the efficacy of a simulated human dose of 600 mg ceftaroline fosamil–600 mg avibactam every 8 h as a 1-h infusion in a polymicrobial
in vivo
murine model. Seven isolates were used (3 methicillin-resistant
Staphylococcus aureus
[MRSA] isolates, 1 methicillin-susceptible
S. aureus
[MSSA] isolate, 1
Escherichia coli
isolate, 1
Enterobacter cloacae
isolate, and 1
Bacteroides fragilis
isolate) in various combinations in an immunocompromised polymicrobial tissue infection to assess the efficacy of the simulated regimen. Each infection was comprised of at least one
S. aureus
isolate with a MIC of 0.25 to 1 μg/ml and one
Enterobacteriaceae
isolate with a MIC of 1 or 4 μg/ml. Eight of 16 infections also included
B. fragilis
, with a MIC of 0.5 μg/ml, as a third organism. Efficacy was evaluated after 24 h as the change in log
10
CFU from the level of 0-h controls. Efficacy was seen against all isolate combinations, with at least a 1-log kill against
Enterobacteriaceae
and a minimum of a 2-log kill against
S. aureus
and
B. fragilis
isolates. These bacterial reductions correlate with free drug concentration above the MIC (
f
T>MIC) produced by the humanized regimen of 100, 86, and 56% at MICs of 1, 2, and 4 μg/ml, respectively. The humanized regimen of 600 mg ceftaroline fosamil–600 mg avibactam every 8 h as a 1-h infusion showed predictable efficacy against all infections tested in this model. These data support further clinical investigation of ceftaroline fosamil-avibactam for the treatment of polymicrobial tissue infections.
Identification of Novel Genes Responsible for Overexpression of
ampC
in Pseudomonas aeruginosa PAO1
Authors: Tsutsumi Yuko , Tomita Haruyoshi , Tanimoto Koichi 
Published: September 2013

ABSTRACT

The development of resistance to antipseudomonal penicillins and cephalosporins mediated by the chromosomal
ampC
gene in
Pseudomonas aeruginosa
is of clinical importance. We isolated piperacillin-resistant mutants derived from
P. aeruginosa
PAO1 and analyzed two mutants that had an insertion in
mpl
and
nuoN
. One mutant, YT1677, was resistant to piperacillin and ceftazidime and had an insertion in
mpl
, which encodes UDP-
N
-acetylmuramate:
l
-alanyl-γ-
d
-glutamyl-
meso
-diaminopimelate ligase. The other mutant, YT7988, showed increased MICs of piperacillin, ceftazidime, cefepime, and cefoperazone, and the insertion was mapped to
nuoN
, which encodes NADH dehydrogenase I chain N. Complementation experiments demonstrated that these mutations resulted in higher levels of resistance to β-lactams. The expression of genes reported to be involved in β-lactam resistance was examined by real-time PCR in YT1677 and YT7988 mutants. Overexpression was observed for only
ampC
, and other genes were expressed normally. Deletion of the
ampR
gene in YT1677 and YT7988 resulted in decreased expression of
ampC
, indicating that the mutations in YT1677 and YT7988 affected the expression of
ampC
through the function of AmpR.
Carbapenemase-Producing Enterobacteriaceae in Spain in 2012
Authors: Oteo Jesús , Saez David , Bautista Verónica , Fernández-Romero Sara , Hernández-Molina Juan Manuel , Pérez-Vázquez María , Aracil Belén , Campos José 
Published: September 2013

ABSTRACT

We report the epidemiological impact of carbapenemase-producing
Enterobacteriaceae
(CPE) in Spain in 2012. Of the 237 carbapenemases detected, 163 were from the OXA-48 group, 60 were from VIM-1, 8 were from KPC-2, 5 were from IMP, and 1 was from NDM-1. Interhospital spread of carbapenemase-producing
Klebsiella pneumoniae
was due to a limited number of multilocus sequence types (MLST) and carbapenemase types, including ST15–VIM-1, ST11–OXA-48, ST405–OXA-48, ST101–KPC-2, and ST11–VIM-1. The number of CPE cases in Spain has increased sharply in recent years, due mainly to the emergence of OXA-48.
Predicting
In Vivo
Efficacy of Therapeutic Bacteriophages Used To Treat Pulmonary Infections
Authors: Henry Marine , Lavigne Rob , Debarbieux Laurent 
Published: September 2013

ABSTRACT

The potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis of
in vitro
observations, the parameters used to guide their choice among billions of available bacteriophages are still not clearly defined. We made use of a mouse lung infection model and a bioluminescent strain of
Pseudomonas aeruginosa
to compare the activities
in vitro
and
in vivo
of a set of nine different bacteriophages (PAK_P1, PAK_P2, PAK_P3, PAK_P4, PAK_P5, CHA_P1, LBL3, LUZ19, and PhiKZ). For seven bacteriophages, a good correlation was found between
in vitro
and
in vivo
activity. While the remaining two bacteriophages were active
in vitro
, they were not sufficiently active
in vivo
under similar conditions to rescue infected animals. Based on the bioluminescence recorded at 2 and 8 h postinfection, we also define for the first time a reliable index to predict treatment efficacy. Our results showed that the bacteriophages isolated directly on the targeted host were the most efficient
in vivo
, supporting a personalized approach favoring an optimal treatment.
Pharmacokinetic-Pharmacodynamic Analyses for Efficacy of Ceftaroline Fosamil in Patients with Community-Acquired Bacterial Pneumonia
Authors: Bhavnani Sujata M. , Hammel Jeffrey P. , Van Wart Scott A. , Rubino Christopher M. , Reynolds Daniel K. , Forrest Alan , Khariton Tatiana , Friedland H. David , Riccobene Todd A. , Ambrose Paul G. 
Published: September 2013

ABSTRACT

Pharmacokinetic-pharmacodynamic (PK-PD) analyses for efficacy using phase III trial data from patients treated with a ceftaroline fosamil dosing regimen of 600 mg intravenously (i.v.) every 12 h (q12h) for 5 to 7 days for community-acquired bacterial pneumonia (CABP) were conducted. High clinical and microbiological success rates (84.7 and 86.3%, respectively) and percentages of time during the dosing interval that free-drug steady-state concentrations remained above the MIC (
f
%
T
>MIC) (98.4% had
f
%
T
>MIC values of ≥63.3) were observed among 124 microbiologically evaluable patients. As a result, significant PK-PD relationships could not be identified. These data provide support for the use of a ceftaroline fosamil dosing regimen of 600 mg i.v. q12h to treat patients with CABP.
Cell Death of Gamma Interferon-Stimulated Human Fibroblasts upon Toxoplasma gondii Infection Induces Early Parasite Egress and Limits Parasite Replication
Authors: Niedelman Wendy , Sprokholt Joris K. , Clough Barbara , Frickel Eva-Maria , Saeij Jeroen P. J. 
Published: September 2013

ABSTRACTThe intracellular protozoan parasiteToxoplasma gondiiis a major food-borne illness and opportunistic infection for the immunosuppressed. Resistance toToxoplasmais dependent on gamma interferon (IFN-γ) activation of both hematopoietic and nonhematopoietic cells. Although IFN-γ-induced innate immunity in nonhematopoietic cells has been extensively studied in mice, it remains unclear what resistance mechanisms are relied on in nonhematopoietic human cells. Here, we report an IFN-γ-induced mechanism of resistance toToxoplasmain primary human foreskin fibroblasts (HFFs) that does not depend on the deprivation of tryptophan or iron. In addition, infection is still controlled in HFFs deficient in the p65 guanylate binding proteins GBP1 or GBP2 and the autophagic protein ATG5. Resistance is coincident with host cell death that is not dependent on the necroptosis mediator RIPK3 or caspases and is correlated with early egress of the parasite before replication. This IFN-γ-induced cell death and early egress limits replication in HFFs and could promote clearance of the parasite by immune cells.
Functional Comparison of Plasmodium falciparum Transmission-Blocking Vaccine Candidates by the Standard Membrane-Feeding Assay
Authors: Miura Kazutoyo , Takashima Eizo , Deng Bingbing , Tullo Gregory , Diouf Ababacar , Moretz Samuel E. , Nikolaeva Daria , Diakite Mahamadou , Fairhurst Rick M. , Fay Michael P. , Long Carole A. , Tsuboi Takafumi 
Published: September 2013

ABSTRACT

Recently, there has been a renewed interest in the development of transmission-blocking vaccines (TBV) against
Plasmodium falciparum
malaria. While several candidate TBVs have been reported, studies directly comparing them in functional assays are limited. To this end, recombinant proteins of TBV candidates Pfs25, Pfs230, and PfHAP2 were expressed in the wheat germ cell-free expression system. Outbred CD-1 mice were immunized twice with the antigens. Two weeks after the second immunization, IgG levels were measured by enzyme-linked immunosorbent assay (ELISA), and IgG functionality was assessed by the standard membrane-feeding assay (SMFA) using cultured
P. falciparum
NF54 gametocytes and
Anopheles stephensi
mosquitoes. All three recombinant proteins elicited similar levels of antigen-specific IgG judged by ELISA. When IgGs purified from pools of immune serum were tested at 0.75 mg/ml in the SMFA, all three IgGs showed 97 to 100% inhibition in oocyst intensity compared to control IgG. In two additional independent SMFA evaluations, anti-Pfs25, anti-Pfs230, and anti-PfHAP2 IgGs inhibited oocyst intensity in a dose-dependent manner. When all three data sets were analyzed, anti-Pfs25 antibody showed significantly higher inhibition than the other two antibodies (
P
< 0.001 for both), while there was no significant difference between the other two (
P
= 0.15). A proportion of plasma samples collected from adults living in an area of malaria endemicity in Mali recognized Pfs230 and PfHAP2. This is the first study showing that the HAP2 protein of
P. falciparum
can induce transmission-blocking antibody. The current study supports the possibility of using this system for a comparative study with multiple TBV candidates.
Development and initial validation of a new outcome measure for hospice and palliative care: the St Christopher's Index of Patient Priorities (SKIPP)
Authors: Addington-Hall Julia , Hunt Katherine , Rowsell Ali , Heal Rosanna , Hansford Penny , Monroe Barbara , Sykes Nigel 
Published: September 2013

ObjectiveTo develop and conduct a preliminary psychometric analysis of a hospice and palliative care patient-reported outcome measure to detect patients’ perceptions of change in quality of life (QoL) and issues of concern, and views of service benefit.MethodsFollowing pilot testing and cognitive interviewing, St Christopher's Index of Patient Priorities (SKIPP) was administered twice to hospice inpatients and homecare patients. QoL was rated ‘now’, and retrospectively ‘before starting hospice care’ or ‘at the time of the first interview’. Patients nominated and rated progress with main concerns, rated the difference the service was making, and completed palliative care outcome scale. Patients completed SKIPP again within 24 h to measure test-retest reliability.ResultsQoL scores ‘now’ differed significantly from retrospective scores made at same time: QoL increased with hospice care when patients ‘looked back’ on previous QoL. Four-fifths reported that their first concern had got ‘a little’/ ‘much’ better since initial service contact: this declined subsequently. Four-fifths at both time points said the hospice had made ‘a lot of difference’ to them. No significant differences were noted between time points on palliative care outcome scale items. Test-retest analyses were prevented by low numbers.ConclusionsSKIPP can detect patients’ perception of change in QoL and main concerns, and the difference patients think the service has made to them. Its design with current and retrospective components addresses response shift and means it can be used for quality improvement or clinical purposes with only one administration, an advantage in frail populations. It is therefore a useful addition to hospice and palliative care patient-reported outcome measures.
Routine urinalysis in patients with a blunt abdominal trauma mechanism is not valuable to detect urogenital injury
Authors: Olthof Dominique C , Joosse Pieter , van der Vlies Cornelis H , de Reijke Theo M , Goslings J Carel 
Published: September 2013

ObjectiveTo investigate whether the routine performance of urinalysis in patients with a blunt trauma mechanism is still valuable.MethodsConsecutive patients aged ≥16 years, admitted to a Dutch Level 1 trauma centre between January 2008 and August 2011, were included in this retrospective cohort study. Results of urinalysis (erythrocytes per µL) were divided into no, microscopic or macroscopic haematuria. Patients were divided into four groups based on whether a urinalysis was performed or not, with or without imaging for urogenital injury. Main outcome measures were the presence of urogenital injury and whether the findings on urine specimen and/or imaging led to clinical consequences.ResultsA total of 1815 patients were included. The prevalence of intra-abdominal and urogenital injuries was 13% and 8%, respectively. In 1363 patients (75%), urinalysis was performed and 1031 patients (57%) underwent imaging for urogenital injury as well. The presence of macroscopic haematuria (n=16) led to clinical consequences in 73% of the patients (11 out of 15), regardless of the findings on imaging. Microscopic haematuria on urinalysis in combination with no findings on imaging led to clinical consequences in 8 out of 212 patients (4%). Microscopic haematuria on urinalysis in patients who did not have imaging for urogenital injury did not lead to clinical consequences (0 out of 54 patients; 0%). All the 8 patients who underwent an intervention had positive findings on imaging.ConclusionsThe results do not support the routine performance of urinalysis in patients admitted with a blunt trauma mechanism. Although urinalysis could be valuable in specific patient populations, we should consider omitting this investigation as a routine part of the assessment of trauma patients.