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Changes in the number of synaptic AMPA receptors underlie many forms of synaptic plasticity. These variations are controlled by an interplay between their intracellular transport (IT), export to the plasma membrane (PM), stabilization at synapses, and recycling. The cytosolic C-terminal domain of the AMPAR GluA1 subunit is specifically associated with 4.1 N and SAP97. We analyze how interactions between GluA1 and 4.1N or SAP97 regulate IT and exocytosis in basal conditions and after cLTP induction. The down-regulation of 4.1N or SAP97 decreases GluA1 IT properties and export to the PM. The total deletion of its C-terminal fully suppresses its IT. Our results demonstrate that during basal transmission, the binding of 4.1N to GluA1 allows their exocytosis whereas the interaction with SAP97 is essential for GluA1 IT. During cLTP, the interaction of 4.1N with GluA1 allows its IT and exocytosis. Our results identify the differential roles of 4.1N and SAP97 in the control of various phases of GluA1 IT. [ABSTRACT FROM AUTHOR]

Surveys 85 health care professionals on the learning difficulties of diabetic patients. Results show that educators find it easy to teach techniques: patients master procedures well and make few mistakes. In contrast, diabetic patients seem to have problems learning skills, such as insulin dose adjustment, that require complex problem-solving. (Author/GCP)

Background Intra-atrial reentrant tachycardia (IART) is a frequent arrhythmia in patients with Fontan circulation. Although its supraventricular origin, such arrhythmia can be poorly tolerated as it leads to haemodynamic impairment. Concomitant assessment of pressure/volume overload of cardiac chambers due to valvular disease or residual shunts is necessary. Case summary We report the case of a 33-year-old male with Fontan extracardiac conduit, suffering from IART with initial poor haemodynamic tolerance. He had a medical history of pulmonary atresia with intact ventricular septum and Type 0 bicuspid aortic valve, with a total of four cardiac surgeries. Echocardiography demonstrated a severe impairment of the univentricular ejection fraction and a critical aortic stenosis. Given the limited medical treatment options of the arrhythmia and the risks of another heart surgery, both IART ablation and transcatheter aortic valve replacement (TAVR) were performed during the same procedure. The IART critical isthmus located in the antero-lateral region of the extracardiac conduit was effectively treated with radiofrequency. Rapid pacing during TAVR was provided by a catheter placed in the unique ventricle via a transconduit puncture. The aortic valve was deployed with minimal para-valvular regurgitation and a satisfactory transvalvular gradient. At follow-up, the univentricular ejection fraction normalized and no arrhythmic episode was recorded in absence of anti-arrhythmic drugs. Discussion This case highlights the need of a collaborative approach for treating complex cases of adult congenital heart disease, suffering from both electrophysiological and haemodynamic disorders. This combination offered an elegant and safest solution for treating concomitantly a life-threatening arrhythmia and an aortic stenosis. [ABSTRACT FROM AUTHOR]

Electrochemical pressure impedance spectroscopy (EPIS) has recently been developed as a potential diagnosis tool for polymer electrolyte membrane fuel cells (PEMFC). It is based on analyzing the frequency response of the cell voltage with respect to an excitation of the gas-phase pressure. We present here a combined modeling and experimental study of EPIS. A pseudo-twodimensional PEMFC model was parameterized to a 100 cmy cell installed in its test bench, and used to reproduce steady-state cell polarization and electrochemical impedance spectra (EIS). Pressure impedance spectra were obtained both in experiment and simulation by applying a harmonic pressure excitation at the cathode outlet. The model shows good agreement with experimental data for current densities ≤ 0.4 A cm-2. Here it allows a further simulative analysis of observed EPIS features, including the magnitude and shape of spectra. Key findings include a strong influence of the humidifier gas volume on EPIS and a substantial increase in oxygen partial pressure oscillations towards the channel outlet at the resonance frequency. At current densities ≥ 0.8 A cm-2 the experimental EIS and EPIS data cannot be fully reproduced. This deviation might be associated with the formation and transport of liquid water, which is not included in the model. [ABSTRACT FROM AUTHOR]

In view to proposing an alternative to oversized energy sources currently installed in electric vehicles for suburban transport, a direct hybrid fuel cell (FC)-supercapacitors (SC) source has been designed and tested on a test bench. The rated 15.6 kW source--with an air-cooled 5.6 kW FC and a 165 F SC storage device--was shown perfectly suited to traction of a 520 kg vehicle along the NEDC cycle, then validating the previously developed concept of a one-ton car propelled by a 10 kW FC in the rated 30 kW hybrid source for this cycle. In comparison with a FC used alone, hybridization was shown to allow the power demand for the cell to vary in quite a narrower range, as formerly observed. Moreover, the rates of fuel cell voltage and current generated in the driving cycle, were shown to be reduced by one order of magnitude by the direct hybridization which is to contribute to the FC durability. Two operating parameters were shown to have a significant effect on the hybrid source efficiency, namely the capacity of the SC at 110 or 165 F, and the recovery of deceleration power--emulated by an external power supply--which can decrease by 25% the fuel consumption in NEDC cycle conditions, as predicted by the model. [ABSTRACT FROM AUTHOR]

Summary Cold-triggered pain is essential to avoid prolonged exposure to harmfully low temperatures. However, the molecular basis of noxious cold sensing in mammals is still not completely understood. Here, we show that the voltage-gated Nav1.9 sodium channel is important for the perception of pain in response to noxious cold. Nav1.9 activity is upregulated in a subpopulation of damage-sensing sensory neurons responding to cooling, which allows the channel to amplify subthreshold depolarizations generated by the activation of cold transducers. Consequently, cold-triggered firing is impaired in Nav1.9 − / − neurons, and Nav1.9 null mice and knockdown rats show increased cold pain thresholds. Disrupting Nav1.9 expression in rodents also alleviates cold pain hypersensitivity induced by the antineoplastic agent oxaliplatin. We conclude that Nav1.9 acts as a subthreshold amplifier in cold-sensitive nociceptive neurons and is required for the perception of cold pain under normal and pathological conditions. [ABSTRACT FROM AUTHOR]

Physical contact with the external world occurs through specialized neural structures called mechanoreceptors. Cutaneous mechanoreceptors provide information to the central nervous system (CNS) about touch, pressure, vibration, and skin stretch. The physiological function of these mechanoreceptors is to convert physical forces into neuronal signals. Key questions concern the molecular identity of the mechanoelectric transducer channels and the mechanisms by which the physical parameters of the mechanical stimulus are encoded into patterns of action potentials (APs). Compelling data indicate that the biophysical traits of mechanosensitive channels combined with the collection of voltage-gated channels are essential to describe the nature of the stimulus. Recent research also points to a critical role of the auxiliary cell-nerve ending communication in encoding stimulus properties. This review describes the characteristics of ion channels responsible for translating mechanical stimuli into the neural codes that underlie touch perception and pain. [ABSTRACT FROM AUTHOR]

Abstract: Inhibition of platinum surfaces by carbon monoxide, in particular in polymer membrane electrolyte fuel cells (PEMFC) has been observed for decades by electrochemists. Significant effects have been observed in the hydrogen stream fed to the anode of the fuel cell with concentrations ranging from 1 to 100ppm depending on the operating conditions e.g. temperature, pressure and excess in reacting gases. As a matter of fact, the gas composition and the surface coverage by CO and H2 vary in the cell, because of the hydrogen consumption at the anode: this is to result to non-uniform distributions of electrode poisoning, current density, and overvoltage, from the inlet to the outlet of the cell. A simple 1D-model has been developed for prediction of the profiles of the above variables in the fuel cells, with the support of experimental data obtained with a 25cm2 PEMFC: interpretation of polarization curves and impedance spectra yielded the kinetic laws of the two electrode reactions, with both neat hydrogen and CO-containing hydrogen at ppm levels. Simulations show that for low excess in hydrogen – as for practical use of fuel cells – the coverage fractions of the various species can greatly vary in the cell, resulting in non-uniform distributions of current density in the cell and enhanced electrode poisoning near the cell outlet. In contrast working with very high hydrogen excess, as can be done at bench scale, leads to uniform behaviour of the cell, and far less visibility of the anode poisoning by carbon monoxide. [Copyright &y& Elsevier]

Thoracic aortic aneurysm and aortic dissection (TAA and AD) are an important cause of sudden death. Familial cases could account for 20% of all cases. A genetic heterogeneity with two identified genes (FBN1 and COL3A1) and three loci (3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-24) has been shown previously. Study of a single family composed of 179 members with an abnormally high occurrence of TAA/AD disease. A total of 40 subjects from three generations were investigated. In addition to five cases of stroke and three cases of sudden death, there were four cases of AD and four cases of TAA in adults. In all, 11 cases of patent ductus arteriosus (PDA) were observed, two of which were associated with TAA and one with AD. Segregation analysis showed that the distribution of these vascular abnormalities was more likely compatible with a single genetic defect with an autosomal dominant pattern of inheritance. There were no clinical signs of Marfan, Elhers-Danlos vascular type or Char syndromes. Genetic linkage analysis was performed for seven genes or loci implicated in familial TAA/AD disease (COL3A1, FBN1, 3p24-25 or MFS2/TAAD2, 5q13-q14 and 11q23.2-q24), Char syndrome (TFAP2B) or autosomal recessive PDA (12q24). Using different genetic models, linkage with these seven loci was excluded. Familial TAA/AD with PDA is likely to be a particular heritable vascular disorder, with an as yet undiscovered Mendelian genetic basis.European Journal of Human Genetics (2004) 12, 173-180. doi:10.1038/sj.ejhg.5201119 Published online 14 January 2004 [ABSTRACT FROM AUTHOR]

Objective: We assessed the effects of glucose–insulin–potassium (GIK) by echocardiography in stable patients with ischemic dysfunction. Methods: Twelve male patients with stable coronary disease (SCD) and ejection fraction (EF) <45% were studied for systolic function. GIK (glucose 30%, 300 insulin units and KCl 6 g/l) was infused at 1 ml/kg per h over 20 min. Hemodynamic and echocardiographic measurements were recorded at rest (T0), at the end (20 min) of GIK infusion (T+20), 20 and 40 min after the end of the infusion (T+40 and T+60). Results: At T+20, a significant decrease in WMSI (wall motion score index) was observed compared with T0 (2.16±0.14 vs. 2.30±0.16: P<0.05). An increase in EF was reported at T+40 and T+60 compared with T0 (44.1±7.8% and 53.3±11.6% vs. 35.6±4.5%, respectively: P<0.01). A decrease in WMSI was observed at T+40 and T+60 compared with rest (2.02±0.17 and 1.93±0.11 vs. 2.30±0.16, respectively: P<0.01). Conclusion: Our present work suggests that GIK infusion improves systolic function in patients with SCD and ejection fraction <45%. Further studies are needed to determine if short-term GIK infusion could be useful for therapeutic or diagnostic strategies in these patients. [Copyright &y& Elsevier]

Antiphospholipid syndrome (APS) is one of several prothrombotic states in which thrombi occur within both the venous and arterial beds. A minority of patients with APS present with an acute and devastating syndrome characterized by multiple simultaneous vascular occlusions throughout the body. “Catastrophic APS” is defined by the clinical involvement of at least three different organ systems over a period of days or weeks with histological evidence of multiple occlusions of large or small vessels. We report the case of a 16-year-old girl referred to our paediatric cardiology unit for NHYA IV and a blowing systolic murmur at the apex radiating to the left axilla. Transthoracic echocardiography (TTE) revealed mitral valve leaflet thickening with vegetations (13mm) on the edges of both leaflets and moderate mitral regurgitation (MR) (image 1). The diagnosis of Libman-Sacks or non-bacterial thrombotic endocarditis secondary to antiphospholipid syndrome was suggested by repeated negative blood cultures along with persistently elevated anticardiolipin antibody titers. The condition deteriorated to acute thrombotic microangiopathy affecting multiple organs with arterial hypertension and thrombocytopenia. Anticoagulation with warfarin was peformed and aspirin, corticosteroids and ACE inhibitors were given. TTE follow-up after 1.5 years revealed no recurrence of MR with normal mitral valve leaflets. Conclusion: In catastrophic APS an aggressive therapeutic approach is warranted. Valve lesions may become more severe during long term follow-up. Display Omitted [ABSTRACT FROM AUTHOR]

Purpose: When isolated and non immune, prevalence of congenital and childhood atrioventricular blocks (AVB) is extremely low and little is known about their natural history. Methods: A multicentric study retrospective from 1980 to 2009 allowed inclusion of 141 children from 13 French referral centers. Included children presented an AVB diagnosed in utero, at birth or during childhood before the age of 15 years, without structural heart abnormalities and without maternal antibodies. Results: 26 congenital and 114 childhood AVB were included. Symptoms lead to diagnosis in 15,6% whereas AVB was asymptomatic in 84,4%. 73% AVB were complete and 26,2% AVB were incomplete at first presentation. 21 of these incomplete blocks (56,7%) progressed to permanent complete AVB. Narrow QRS complexes were found in 69,2% congenital and 91,2% childhood AVB. In the 112 (79,4%) implanted children, mean duration between AVB diagnosis and pacemaker implantation was 35 months. Pacemaker primo-implantation occurred during the first year of life for 18 children and 90 children (63.8%) were paced before 10 years old. Pacing was required for symptomatic bradycardia in 37,5% whereas prophylactic cardiac pacing accounted for 61,6%. The median follow-up was 96 months (from 6 to 384 months). 85,1% experienced no complication and neither dilated cardiomyopathy nor death had occurred at last follow-up. Pacemaker-related complications appeared in 11,6%. Conclusion: We describe the largest reported experience with isolated and non immune congenital and childhood AVB. Such a block is a nodal damage from unknown origin that may postnatally progress in incomplete forms. Outcome is not influenced by age at diagnosis. Prognosis is very good with no late-onset dilated cardiomyopathy, a few pacemaker-related complications in the modern technological era and no death at last follow-up. [ABSTRACT FROM AUTHOR]

Primary cardiac tumors are rare with an estimated incidence of 0.27% in pediatric autopsies. The most common type of cardiac tumor identified in infancy and childhood is rhabdomyoma. We report a case of prenatal diagnosis of multiples cardiac rhabdomyoma at 29 weeks of gestation. Full-term delivery was straightforward without hydrops and dysrhythmia. In the immediate post-natal period, cyanosis appeared, and echocardiography showed multiple cardiac rhabdomyoma and severe right ventricular outflow tract obstruction (Image 1). Aprostadil perfusion was necessary. Aorto-pulmonary anastomisis was performed with success. The diagnosis of cardiac rhabdomyoma was confirmed histologically and tuberous sclerosis by molecular genetic analysis. Renal echocardiography was normal and cerebral MRI was not perfomed. Fourteen months later, neurodevelopment was normal. Echocardiography confirmed regression of the cardiac tumors with disappearance of the severe right ventricular outflow tract obstruction. ECG monitoring was normal. Conclusion: The natural history of most cardiac rhabdomyoma is favorable with tumors regressing (completely or partially). Surgical resection of the tumors is required for severe ventricular outflow tract obstruction. Aorto-pulmonary anastomosis, as in our case with severe right ventricular outflow tract obstruction, is an alternative treatment because regression and even complete resolution of more than 80% of the tumors occurs during infancy and early childhood. Display Omitted [ABSTRACT FROM AUTHOR]

Introduction: Patient selection for percutaneous pulmonary valve insertion PPVI is widely accepted, being limited to patients having a right ventricle to pulmonary artery conduit. Little data has been reported regarding PPVI on patients having a native RVOT. We present our data regarding percutaneous PPVI in native RVOT and discuss the specific requirements to make this technique safe and durable. Patients and methods: We review patients included over the last 12 months in the prospective study (REVALV) for patients undergoing RVOT intervention for severe stenosis and/or insufficiency. Only valved stent on native RVOT group is analyzed here. 10 patients were included. We perform MRI, balloon calibration and angiography of the RVOT to all patients in order to define the RVOT morphology, and to establish a personalized technique for each patient in order to implant a valved stent on the native RVOT. All patients undergoing valved stent implantation are previously pre-stented with a bare metal stent according to present recommendations. Results: Initial dimensions for these patients were on the upper limit for the established criteria. 2 had a diameter above 24mm. Decision for implanting valved stent was taken based on the fact that pre-stenting reduces RVOT diameter acchieving 22mm, and giving the native outflow track the stability to prevent valved-stent fractures. For one patient, left pulmonary branch was stented down to the pulmonary trunk in order to have an appropriate diameter for valved-stenting. Pulmonary valve was placed successfully in all cases. All but one had been pre-stented at same procedure than valvulation. Of those, one freshly implanted bare metal stent dislodged to the right pulmonary artery when tenting to place the delivery system for the percutaneous valve. Two extra bare metal stents were implanted in order to cover the branch to the trunk, and finally valved stent was placed with no further problems. Conclusions: Percutaneous pulmonary valve implantation can be performed on patients having native RVOT with success. Pre-stenting should be performed in a previous intervention in order to ensure stabilization of the bare metal stent and to avoid dislodgements. MRI, angiography and balloon calibration are not discriminating criteria for discarding candidates if personalized techniques are established for each patient. Pulmonary branches can be used as anchors for PPVI. [Copyright &y& Elsevier]