bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of natriuretic peptides on electrical conduction in the sinoatrial node and atrial myocardium of the heart
Authors: Azer John , Hua Rui , Krishnaswamy Pooja S. , Rose Robert A. 
Published: December 2013

Key points
Natriuretic peptides are powerful regulators of the cardiovascular system, but their direct electrophysiological effects in the heart are poorly understood.
We have used optical mapping techniques to determine the effects of B‐type and C‐type natriuretic peptide (BNP and CNP) as well as their receptors (NPR‐A, NPR‐B and NPR‐C) on electrical conduction in the sinoatrial node and atrial myocardium.
In basal conditions, BNP and CNP speed conduction within the sinoatrial node (SAN) and into the atrial myocardium in association with shifts in the initial exit site by activating NPR‐A and NPR‐B.
In the presence of isoproterenol, BNP and CNP have the opposite effect whereby conduction in the SAN and atria is slowed. These inhibitory effects are due to the activation of NPR‐C as well as NPR‐A/B.
We conclude that natriuretic peptides have potent effects on electrical conduction in the heart. These effects are complex and can involve multiple natriuretic peptide receptors.
AbstractNatriuretic peptides, including B‐type and C‐type natriuretic peptide (BNP and CNP), are powerful regulators of the cardiovascular system; however, their electrophysiological effects in the heart, particularly in the sinoatrial node (SAN), are incompletely understood. We have used high‐resolution optical mapping to measure the effects of BNP and CNP, and the roles of natriuretic peptide receptors (NPR‐A, NPR‐B and NPR‐C), on electrical conduction within the SAN and atrial myocardium. In basal conditions BNP and CNP (50–500 nm) increased conduction velocity (CV) within the SAN by ∼30% at the high dose and shifted the initial exit site superiorly. These effects sped conduction from the SAN to the surrounding atrial myocardium and were mediated by the NPR‐A and NPR‐B receptors. In the presence of isoproterenol (1 μm) the NPR‐C receptor made a major contribution to the effects of BNP and CNP in the heart. In these conditions BNP, CNP and the NPR‐C agonist cANF each decreased SAN CV and shifted the initial exit site inferiorly. The effects of cANF (30% reduction) were larger than BNP or CNP (∼15% reduction), indicating that BNP and CNP activate multiple natriuretic peptide receptors. In support of this, the inhibitory effects of BNP were absent in NPR‐C knockout mice, where BNP instead elicited a further increase (∼25%) in CV. Measurements in externally paced atrial preparations demonstrate that the effects of natriuretic peptides on CV are partially independent of changes in cycle length. These data provide detailed novel insight into the complex effects of natriuretic peptides and their receptors on electrical conduction in the heart.
Clinical Pharmacodynamics of Antipseudomonal Cephalosporins in Patients with Ventilator-Associated Pneumonia
Authors: MacVane Shawn H. , Kuti Joseph L. , Nicolau David P. 
Published: December 2013

ABSTRACT

Advanced-generation cephalosporins are frequently used for empirical coverage of ventilator-associated pneumonia (VAP) due to their activity against a broad spectrum of Gram-positive and Gram-negative aerobic bacteria, including
Pseudomonas aeruginosa
and
Enterobacteriaceae
. Providing optimal antibiotic exposure is essential to achieving successful response in patients with VAP. We evaluated exposures of two antipseudomonal cephalosporins, ceftazidime and cefepime, in patients with VAP due to Gram-negative bacilli to identify the pharmacodynamic parameter predictive of microbiological success. Population pharmacokinetic models were used to estimate individual free drug exposures. Pharmacodynamic indices were determined for each patient using the baseline Gram-negative bacilli with the highest drug MIC. Classification and regression tree analysis was utilized to partition exposure breakpoints, and multivariate logistic regression was conducted to identify predictors of microbiological success. A total of 73 patients (18 receiving ceftazidime therapy and 55 receiving cefepime therapy) were included. MICs ranged widely from 0.047 to 96 μg/ml. The microbiological success rate was 58.9%. Predictive breakpoints were identified for all pharmacodynamic parameters, including a serum
f
T > MIC greater than 53% (
P
= 0.02). When controlling for APACHE II (odds ratio [OR], 1.01; 95% confidence interval, 0.93 to 1.09;
P
= 0.85) and combination therapy (OR, 0.74; 95% confidence interval, 0.25 to 2.19;
P
= 0.59), achieving a greater than 53%
f
T > MIC remained a significant predictor of success (OR, 10.3; 95% confidence interval, 1.1 to 92.3;
P
= 0.04). In patients with VAP due to Gram-negative bacilli, serum exposure of greater than 53%
f
T > MIC was found to be a significant predictor of favorable microbiological response for antipseudomonal cephalosporins. These data are useful when determining dosing regimens for cephalosporin agents under development for pneumonia.
Antibiotic Activity against Naive and Induced Streptococcus pneumoniae Biofilms in an
In Vitro
Pharmacodynamic Model
Authors: Vandevelde Nathalie M. , Tulkens Paul M. , Van Bambeke Françoise 
Published: December 2013

ABSTRACT

Biofilms play a role in the pathogenicity of pneumococcal infections. A pharmacodynamic
in vitro
model of biofilm was developed that allows characterization of the activity of antibiotics against viability and biomass by using in parallel capsulated (ATCC 49619) and noncapsulated (R6) reference strains. Naive biofilms were obtained by incubating fresh planktonic cultures for 2 to 11 days in 96-well polystyrene plates. Induced biofilms were obtained using planktonic bacteria collected from the supernatant of 6-day-old naive biofilms. Biomass production was more rapid and intense in the induced model, but the levels were similar for both strains. Full concentration responses fitting sigmoidal regressions allowed calculation of maximal efficacies and relative potencies of drugs. All antibiotics tested (amoxicillin, clarithromycin, solithromycin, levofloxacin, and moxifloxacin) were more effective against young naive biofilms than against old or induced biofilms, except macrolides/ketolides, which were as effective at reducing viability in 2-day-old naive biofilms and in 11-day-old induced biofilms of R6. Macrolides/ketolides, however, were less potent than fluoroquinolones against R6 (approximately 5- to 20-fold-higher concentrations needed to reduction viability of 20%). However, at concentrations obtainable in epithelial lining fluid, the viabilities of mature or induced biofilms were reduced 15 to 45% (amoxicillin), 17 to 44% (macrolides/ketolides), and 12 to 64% (fluoroquinolones), and biomasses were reduced 5 to 45% (amoxicillin), 5 to 60% (macrolides/ketolides), and 10 to 76% (fluoroquinolones), with solithromycin and moxifloxacin being the most effective and the most potent agents (due to lower MICs) in their respective classes. This study allowed the ranking of antibiotics with respect to their potential effectiveness in biofilm-related infections, underlining the need to search for still more effective options.
Trends in Antibiotic Resistance in Coagulase-Negative Staphylococci in the United States, 1999 to 2012
Authors: May Larissa , Klein Eili Y. , Rothman Richard E. , Laxminarayan Ramanan 
Published: December 2013

ABSTRACT

Coagulase-negative staphylococci (CoNS) are important bloodstream pathogens that are typically resistant to multiple antibiotics. Despite the concern about increasing resistance, there have been no recent studies describing the national prevalence of CoNS pathogens. We used national resistance data over a period of 13 years (1999 to 2012) from The Surveillance Network (TSN) to determine the prevalence of and assess the trends in resistance for
Staphylococcus epidermidis
, the most common CoNS pathogen, and all other CoNS pathogens. Over the course of the study period,
S. epidermidis
resistance to ciprofloxacin and clindamycin increased steadily from 58.3% to 68.4% and from 43.4% to 48.5%, respectively. Resistance to levofloxacin increased rapidly from 57.1% in 1999 to a high of 78.6% in 2005, followed by a decrease to 68.1% in 2012. Multidrug resistance for CoNS followed a similar pattern, and this rise and small decline in resistance were found to be strongly correlated with levofloxacin prescribing patterns. The resistance patterns were similar for the aggregate of CoNS pathogens. The results from our study demonstrate that the antibiotic resistance in CoNS pathogens has increased significantly over the past 13 years. These results are important, as CoNS can serve as sentinels for monitoring resistance, and they play a role as reservoirs of resistance genes that can be transmitted to other pathogens. The link between the levofloxacin prescription rate and resistance levels suggests a critical role for reducing the inappropriate use of fluoroquinolones and other broad-spectrum antibiotics in health care settings and in the community to help curb the reservoir of resistance in these colonizing pathogens.
Imipenem, Meropenem, or Doripenem To Treat Patients with Pseudomonas aeruginosa Ventilator-Associated Pneumonia
Authors: Luyt Charles-Edouard , Aubry Alexandra , Lu Qin , Micaelo Maïté , Bréchot Nicolas , Brossier Florence , Brisson Hélène , Rouby Jean-Jacques , Trouillet Jean-Louis , Combes Alain , Jarlier Vincent , Chastre Jean 
Published: December 2013

ABSTRACT

Only limited data exist on
Pseudomonas aeruginosa
ventilator-associated pneumonia (VAP) treated with imipenem, meropenem, or doripenem. Therefore, we conducted a prospective observational study in 169 patients who developed
Pseudomonas aeruginosa
VAP. Imipenem, meropenem, and doripenem MICs for
Pseudomonas aeruginosa
isolates were determined using Etests and compared according to the carbapenem received. Among the 169 isolates responsible for the first VAP episode, doripenem MICs were lower (
P
< 0.0001) than those of imipenem and meropenem (MIC
50
s, 0.25, 2, and 0.38, respectively); 61%, 64%, and 70% were susceptible to imipenem, meropenem, and doripenem, respectively (
P
was not statistically significant). Factors independently associated with carbapenem resistance were previous carbapenem use (within 15 days) and mechanical ventilation duration before VAP onset. Fifty-six (33%) patients had at least one VAP recurrence, and 56 (33%) died. Factors independently associated with an unfavorable outcome (recurrence or death) were a high day 7 sequential organ failure assessment score and mechanical ventilation dependency on day 7. Physicians freely prescribed a carbapenem to 88 patients: imipenem for 32, meropenem for 24, and doripenem for 32. The remaining 81 patients were treated with various antibiotics. Imipenem-, meropenem-, and doripenem-treated patients had similar VAP recurrence rates (41%, 25%, and 22%, respectively;
P
= 0.15) and mortality rates (47%, 25%, and 22%, respectively;
P
= 0.07). Carbapenem resistance emerged similarly among patients treated with any carbapenem. No carbapenem was superior to another for preventing carbapenem resistance emergence.
The magmatic evolution of three Venusian coronae
Authors: Lang Nicholas P. , López Iván 
Published: December 2013

Abstract

The volcanic and tectonic histories of Venusian coronae appear to be intricately linked. We explore that link through the construction of geological maps of three coronae using Magellan synthetic aperture radar (SAR) imagery and altimetry radar data. Each examined corona – Aramaiti, Bhumidevi and Zemire Coronae – is characterized by an annulus of concentric fractures, lava flows, tholi and clusters of small shields. Radial fractures occur at one corona (Bhumidevi Corona), whereas the other two coronae (Aramaiti and Zemire Coronae) occur within linear fracture belts. Based on observed timing relationships, we propose that the evolution of these three coronae is similar to large silicic caldera formation on Earth in that the formation of concentric fractures facilitated a mass evacuation of a magma reservoir residing underneath each corona resulting in subsequent corona collapse. Our model emphasizes the late-stage evolution of these coronae and predicts that all the erupted products could be basaltic. Such predictions are testable through continued geological mapping of coronae, as well as through
in situ
spectral analyses by Venusian landers.
The Dynamics of Proactive and Reactive Cognitive Control Processes in the Human Brain
Authors: Appelbaum L. Gregory , Boehler C. Nicolas , Davis Lauren A. , Won Robert J. , Woldorff Marty G. 
Published: December 2013

Abstract
In this study, we leveraged the high temporal resolution of EEG to examine the neural mechanisms underlying the flexible regulation of cognitive control that unfolds over different timescales. We measured behavioral and neural effects of color–word incongruency, as different groups of participants performed three different versions of color–word Stroop tasks in which the relative timing of the color and word features varied from trial to trial. For this purpose, we used a standard Stroop color identification task with equal congruent-to-incongruent proportions (50%/50%), along with two versions of the “Reverse Stroop” word identification tasks, for which we manipulated the incongruency proportion (50%/50% and 80%/20%). Two canonical ERP markers of neural processing of stimulus incongruency, the frontocentral negative polarity incongruency wave (NINC) and the late positive component (LPC), were evoked across the various conditions. Results indicated that color–word incongruency interacted with the relative feature timing, producing greater neural and behavioral effects when the task-irrelevant stimulus preceded the target, but still significant effects when it followed. Additionally, both behavioral and neural incongruency effects were reduced by nearly half in the word identification task (Reverse Stroop 50/50) relative to the color identification task (Stroop 50/50), with these effects essentially fully recovering when incongruent trials appeared only infrequently (Reverse Stroop 80/20). Across the conditions, NINC amplitudes closely paralleled RTs, indicating this component is sensitive to the overall level of stimulus conflict. In contrast, LPC amplitudes were largest with infrequent incongruent trials, suggesting a possible readjustment role when proactive control is reduced. These findings thus unveil distinct control mechanisms that unfold over time in response to conflicting stimulus input under different contexts.
Rule Activity Related to Spatial and Numerical Magnitudes: Comparison of Prefrontal, Premotor, and Cingulate Motor Cortices
Authors: Eiselt Anne-Kathrin , Nieder Andreas 
Published: December 2013

Abstract
In everyday situations, quantitative rules, such as “greater than/less than,” need to be applied to a multitude of magnitude comparisons, be they sensory, spatial, temporal, or numerical. We have previously shown that rules applied to different magnitudes are encoded in the lateral PFC. To investigate if and how other frontal lobe areas also contribute to the encoding of quantitative rules applied to multiple magnitudes, we trained monkeys to switch between “greater than/less than” rules applied to either line lengths (spatial magnitudes) or dot numerosities (discrete numerical magnitudes). We recorded single-cell activity from the dorsal premotor cortex (dPMC) and cingulate motor cortex (CMA) and compared it with PFC activity. We found the largest proportion of quantitative rule-selective cells in PFC (24% of randomly selected cells), whereas neurons in dPMC and CMA rarely encoded the rule (6% of the cells). In addition, rule selectivity of individual cells was highest in PFC neurons compared with dPMC and CMA neurons. Rule-selective neurons that simultaneously represented the “greater than/less than” rules applied to line lengths and numerosities (“rule generalists”) were exclusively present in PFC. In dPMC and CMA, however, neurons primarily encoded rules applied to only one of the two magnitude types (“rule specialists”). Our data suggest a special involvement of PFC in representing quantitative rules at an abstract level, both in terms of the proportion of neurons engaged and the coding capacities.
What Role Does the Anterior Temporal Lobe Play in Sentence-level Processing? Neural Correlates of Syntactic Processing in Semantic Variant Primary Progressive Aphasia
Authors: Wilson Stephen M. , DeMarco Andrew T. , Henry Maya L. , Gesierich Benno , Babiak Miranda , Mandelli Maria Luisa , Miller Bruce L. , Gorno-Tempini Maria Luisa 
Published: December 2013

Abstract
Neuroimaging and neuropsychological studies have implicated the anterior temporal lobe (ATL) in sentence-level processing, with syntactic structure-building and/or combinatorial semantic processing suggested as possible roles. A potential challenge to the view that the ATL is involved in syntactic aspects of sentence processing comes from the clinical syndrome of semantic variant primary progressive aphasia (semantic PPA; also known as semantic dementia). In semantic PPA, bilateral neurodegeneration of the ATLs is associated with profound lexical semantic deficits, yet syntax is strikingly spared. The goal of this study was to investigate the neural correlates of syntactic processing in semantic PPA to determine which regions normally involved in syntactic processing are damaged in semantic PPA and whether spared syntactic processing depends on preserved functionality of intact regions, preserved functionality of atrophic regions, or compensatory functional reorganization. We scanned 20 individuals with semantic PPA and 24 age-matched controls using structural MRI and fMRI. Participants performed a sentence comprehension task that emphasized syntactic processing and minimized lexical semantic demands. We found that, in controls, left inferior frontal and left posterior temporal regions were modulated by syntactic processing, whereas anterior temporal regions were not significantly modulated. In the semantic PPA group, atrophy was most severe in the ATLs but extended to the posterior temporal regions involved in syntactic processing. Functional activity for syntactic processing was broadly similar in patients and controls; in particular, whole-brain analyses revealed no significant differences between patients and controls in the regions modulated by syntactic processing. The atrophic left ATL did show abnormal functionality in semantic PPA patients; however, this took the unexpected form of a failure to deactivate. Taken together, our findings indicate that spared syntactic processing in semantic PPA depends on preserved functionality of structurally intact left frontal regions and moderately atrophic left posterior temporal regions, but no functional reorganization was apparent as a consequence of anterior temporal atrophy and dysfunction. These results suggest that the role of the ATL in sentence processing is less likely to relate to syntactic structure-building and more likely to relate to higher-level processes such as combinatorial semantic processing.
A Model-Based Decomposition of the Sea Ice–Atmosphere Feedback over the Barents Sea during Winter
Authors: Liptak Jessica , Strong Courtenay 
Published: December 2013

Abstract
The feedback between Barents Sea ice and the winter atmosphere was studied in a modeling framework by decomposing it into two sequential boundary forcing experiments. The Community Ice Code (CICE) model was initialized with anomalously high sea ice concentration (SIC) over the Barents Sea and forced with an atmosphere produced by positive SIC anomalies, and CICE was initialized with low Barents Sea SIC and forced with an atmosphere produced by negative SIC anomalies. Corresponding control runs were produced by exposing the same SIC initial conditions to climatological atmospheres, and the monthly mean sea ice response showed a positive feedback over the Barents Sea for both experiments: the atmosphere produced by positive SIC anomalies increased SIC over the Barents Sea during the winter, and the atmosphere produced by negative SIC anomalies decreased SIC. These positive feedbacks were driven primarily by thermodynamic forcing from surface longwave flux anomalies and were weakened somewhat by atmospheric temperature advection. Dynamical effects also opposed the positive feedback, with enhanced surface wind stress divergence over the Barents Sea in the high-SIC case and enhanced convergence in the low-SIC case.
Increasing the Dose of Autologous Chondrocytes Improves Articular Cartilage Repair
Authors: Guillén-García Pedro , Rodríguez-Iñigo Elena , Guillén-Vicente Isabel , Caballero-Santos Rosa , Guillén-Vicente Marta , Abelow Stephen , Giménez-Gallego Guillermo , López-Alcorocho Juan Manuel 
Published: December 2013

Background: We hypothesized that implanting cells in a chondral defect at a density more similar to that of the intact cartilage could induce them to synthesize matrix with the features more similar to that of the uninjured one. Methods: We compared the implantation of different doses of chondrocytes: 1 million ( n = 5), 5 million ( n = 5), or 5 million mesenchymal cells ( n = 5) in the femoral condyle of 15 sheep. Tissue generated by microfracture at the trochlea, and normal cartilage from a nearby region, processed as the tissues resulting from the implantation, were used as references. Histological and molecular (expression of type I and II collagens and aggrecan) studies were performed. Results: The features of the cartilage generated by implantation of mesenchymal cells and elicited by microfractures were similar and typical of a poor repair of the articular cartilage (presence of fibrocartilage, high expression of type I collagen and a low mRNA levels of type II collagen and aggrecan). Nevertheless, in the samples obtained from tissues generated by implantation of chondrocytes, hyaline-like cartilage, cell organization, low expression rates of type I collagen and high levels of mRNA corresponding to type II collagen and aggrecan were observed. These histological features, show less variability and are more similar to those of the normal cartilage used as control in the case of 5 million cells implantation than when 1 million cells were used. Conclusions: The implantation of autologous chondrocytes in type I/III collagen membranes at high density could be a promising tool to repair articular cartilage.
Symptomatic Early Osteoarthritis of the Knee Treated With Pulsed Electromagnetic Fields
Authors: Gobbi Alberto , Lad Dnyanesh , Petrera Massimo , Karnatzikos Georgios 
Published: December 2013

Objective: In vitro and in vivo studies have proven a pro-anabolic and anti-catabolic activity within cartilage with the use of pulsed electromagnetic fields (PEMFs). This has piqued interest of sports physicians for its use in the treatment of early osteoarthritis (OA). The aim was to determine if the use of PEMFs in patients with early OA of the knee would lead to an improved clinical outcome. Study design: Prospective case series. Methods: Twenty-two patients aged between 30 and 60 years who underwent treatment with PEMFs (4-hour treatment per day, duration 45 days) were included. All patients presented with symptomatic early OA with grade 0-2 changes (Kellgren-Lawrence classification) at the pretreatment evaluation. Patients were evaluated before treatment, at 1- and 2-year follow-up using visual analogue scale for pain, International Knee Documentation Committee objective, Tegner, and Knee Injury and Osteoarthritis Outcome Scores. Results: A significant improvement in all scores was observed at 1-year follow-up ( P = 0.008). At 2-year follow-up, results deteriorated but were still superior to pretreatment levels ( P = 0.02). No adverse reactions or side effects were seen. Conclusions: This study showed that the use of PEMFs in patients with symptomatic early OA of the knee led to significant improvement in symptoms, knee function, and activity at 1-year follow-up. There was a significant decline in all the scores at 2-year follow-up.