miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

Three-dimensional echocardiography for left ventricular quantification: fundamental validation and clinical applications

One of the earliest applications of clinical echocardiography is evaluation of left ventricular (LV) function and size. Accurate, reproducible and quantitative evaluation of LV function and size is vital for diagnosis, treatment and prediction of prognosis of heart disease. Early three-dimensional (3D) echocardiographic techniques showed better reproducibility than two-dimensional (2D) echocardiography and narrower limits of agreement for assessment of LV function and size in comparison to reference methods, mostly cardiac magnetic resonance (CMR) imaging, but acquisition methods were cumbersome and a lack of user-friendly analysis software initially precluded widespread use. Through the advent of matrix transducers enabling real-time three-dimensional echocardiography (3DE) and improvements in analysis software featuring semi-automated volumetric analysis, 3D echocardiography evolved into a simple and fast imaging modality for everyday clinical use. 3DE provides the possibility to evaluate the entire LV in three spatial dimensions during the complete cardiac cycle, offering a more accurate and complete quantitative evaluation the LV. Improved efficiency in acquisition and analysis may provide clinicians with important diagnostic information within minutes. The current article reviews the methodology and application of 3DE for quantitative evaluation of the LV, provides the scientific evidence for its current clinical use, and discusses its current limitations and potential future directions

A Practical Analysis of Explicit Substitutions Calculi

Explicit substitutions calculi provide a method to compute over -expressions by using first-order term rewriting systems. Many calculi have been proposed that differ by their signature, their number of rules and their theoretical properties. Our aim is to compare these systems from an operational point of view. For a selected class of such calculi, we have developed prototypes written in ELAN. In this paper, we briefly present our first experimental results.

Predicting favourable outcomes in the setting of radiofrequency catheter ablation of long-standing persistent atrial fibrillation A pilot study assessing the value of left atrial appendage peak flow velocity

International audienceBackground Catheter ablation is an effective and potentially curative treatment in patients with atrial fibrillation (AF). Aim To test the hypothesis that left atrial appendage peak flow velocity (LAV) assessed by echocardiography can accurately predict successful catheter ablation as well as favourable outcome in the setting of long-standing persistent AF. Methods This prospective pilot study enrolled 40 patients with long-standing persistent AF (age 60 ± 11 years; persistence of AF 4.2 ± 2 years) who underwent a first catheter ablation procedure using a standardized sequential stepwise protocol. LAV was assessed before the catheter ablation procedure along with classical factors (age, sex, left atrial area, AF cycle length, AF duration and left ventricular ejection fraction), all of which were tested using logistic regression for ability to predict restoration of sinus rhythm during catheter ablation as well as absence of recurrence during a 1-year follow-up. Results Eighteen patients (45%) experienced AF termination during the procedure and 18 patients (45%) did not develop any recurrence during the first 12 months. Multivariable analysis demonstrated that high LAV (> 0.3 m/s) was the only independent predictor of AF termination (odds ratio 5.91, 95% confidence interval 1.06-32.88; P = 0.04) and absence of recurrence at 1 year (odds ratio 4.33, 95% confidence interval 1.05-17.81; P = 0.04). Conclusions This pilot study demonstrated the feasibility and importance of LAV measurement in the setting of long-standing persistent AF to predict successful catheter ablation and favourable mid-term outcome. © 2012 Published by Elsevier Masson SAS

Safety of deferring the reimplantation of pacing systems after their removal for infectious complications in selected patients: A 1-year follow-up study

Introduction: Recent expert consensus guidelines mention that one of the principles for infected device replacement following removal is to "reevaluate carefully if there is a continued need for a new cardiac device replacement." This is a Class I recommendation, which nevertheless suffers from a very low level of evidence (level of evidence C), since no study has revisited the systematic practice of reimplanting the same device based on a meticulous clinical reassessment. In the present paper, we examined the safety of withholding the implantation of pacing systems in selected patients. Methods and Results: Between January 2005 and December 2007, 188 consecutive patients underwent extractions of infected pacing systems at 2 medical centers. "Low-risk" patients were identified by (1) a spontaneous heart rate >45 bpm, (2) no symptomatic asystole during monitoring, (3) QRS duration <120 ms when history of AV block was noted, (4) no high-degree AV block during continuous monitoring. They remained device-free, unless an adverse clinical event occurred mandating the reimplantation. The primary study endpoint was rate of sudden death and syncope after a 12-month follow-up. Among the 74 (39.4%) "low-risk" patients, a single patient suffered a bradycardia-related syncopal event corresponding to a 1.3% (95% CI, 0.0-3.9) rate of primary endpoint. Pacing systems were also reimplanted in 24 patients (32.4%) for syncope (n = 1), nonsevere bradycardia-reated symptoms (n = 17), cardiac resynchronization (n = 2), and for reassurance in 4 asymptomatic patients. Conclusion: After removal of infected pacing systems, these preliminary data demonstrated that a strategy of nonsystematic device reimplantation associated with close surveillance was safe in "low-risk" patients, allowing the administration of antimicrobials in a device-free state. © 2009 Wiley Periodicals, Inc

Impact of Pacing Site on QRS Duration and Its Relationship to Hemodynamic Response in Cardiac Resynchronization Therapy for Congestive Heart Failure

Cardiolog

Electrogram morphology discriminators in implantable cardioverter defibrillators: A comparative evaluation

Contains fulltext : 220908.pdf (Publisher’s version ) (Closed access)BACKGROUND: Morphology algorithms are currently recommended as a standalone discriminator in single-chamber implantable cardioverter defibrillators (ICDs). However, these proprietary algorithms differ in both design and nominal programming. OBJECTIVE: To compare three different algorithms with nominal versus advanced programming in their ability to discriminate between ventricular (VT) and supraventricular tachycardia (SVT). METHODS: In nine European centers, VT and SVTs were collected from Abbott, Boston Scientific, and Medtronic dual- and triple-chamber ICDs via their respective remote monitoring portals. Percentage morphology matches were recorded for selected episodes which were classified as VT or SVT by means of atrioventricular comparison. The sensitivity and related specificity of each manufacturer discriminator was determined at various values of template match percentage from receiving operating characteristics (ROC) curve analysis. RESULTS: A total of 534 episodes were retained for the analysis. In ROC analyses, Abbott Far Field MD (area under the curve [AUC]: 0.91; P < .001) and Boston Scientific RhythmID (AUC: 0.95; P < .001) show higher AUC than Medtronic Wavelet (AUC: 0.81; P < .001) when tested for their ability to discriminate VT from SVT. At nominal % match threshold all devices provided high sensitivity in VT identification, (91%, 100%, and 90%, respectively, for Abbott, Boston Scientific, and Medtronic) but contrasted specificities in SVT discrimination (85%, 41%, and 62%, respectively). Abbott and Medtronic's nominal thresholds were similar to the optimal thresholds. Optimization of the % match threshold improved the Boston Scientific specificity to 79% without compromising the sensitivity. CONCLUSION: Proprietary morphology discriminators show important differences in their ability to discriminate SVT. How much this impact the overall discrimination process remains to be investigated