Sodium-Assisted Formation of Binding and Traverse Conformations of the Substrate in a Neurotransmitter Sodium Symporter Model

Therapeutics designed to increase synaptic neurotransmitter levels by inhibiting neurotransmitter sodium sym- porters (NSSs) classify a strategic approach to treat brain disorders such as depression or epilepsy, however, the critical elementary steps that couple downhill flux of sodium to uphill transport of neurotransmitter are not disti nguished as yet. Here we present modelling of NSS member neuronal GAT1 with the substrate � -aminobutyric acid (GABA), the major inhibitory neurotransmitter. GABA binding is simulated with the occluded conformation of GAT1 homodimer in an ex- plicit lipid/water environment. Simulations performed in the 1-10 ns range of time elucidated persistent formation of half- extended minor and H-bridged major GABA conformations, referred to as binding and traverse conformations, respec- tively. The traverse GABA conformation was further stabilized by GAT1-bound Na + (1). We also observed Na + (1) trans- location to GAT1-bound Cl - as well as the appearance of water molecules at GABA and GAT1-bound Na + (2), conjectur- ing causality. Scaling dynamics suggest that the traverse GABA conformation may be valid for developing substrate in- hibitors with high efficacy. The potential for this finding is significant with impact not only in pharmacology but wherever understanding of the mechanism of neurotransmitter uptake is valuable

A paroxysmalis pitvarfibrilláció kezelésének transzkatéteres ablatiós technikái: új generációs krioballon vagy kontakterő-méréssel kombinált rádiófrekvenciás ablatio?

Absztrakt Bevezetés: A paroxysmalis pitvarfibrilláció eszközös kezelésében elterjedt a kontakterő-méréssel kombinált rádiófrekvenciás ablatio és az új generációs krioballonnal végzett ablatiós módszer. Célkitűzés: A szerzők célja, hogy összehasonlítsák a két ablatiós módszerrel kezelt betegek utánkövetési adatait. Módszer: Prospektív módon 96 (rádiófrekvenciás ablatio: 58, krioballon: 38) beteg (65 férfi, 28–70 év) procedurális és 1 éves utánkövetési adatait elemezték. A beavatkozás után 1, 3, 6 és 12 hónappal EKG-, Holter-monitoros vizsgálat és ambuláns vizit történt. Eredmények: A procedúraidő és a sugáridő a két csoportban: rádiófrekvenciás ablatio: 118,5 ± 15 perc; 15,8 ± 6 perc; krioballon: 73,5 ± 16 perc (p<0,05); 13,8 ± 4,1 perc (p = 0,09) volt. A rádiófrekvenciás csoportban 76,5%, a krioballoncsoportban 81% volt az 1 éves sikerarány. A rádiófrekvenciás csoportban 1 esetben percutan punkcióval kezelhető pericardialis tamponád, a krioballoncsoportban 2 esetben átmeneti nervusphrenicus-bénulás történt. Következtetések: Primer pitvarfibrilláció ablatiót követően a két módszerrel hasonló 1 éves sikerarány érhető el, a krioballon alkalmazásakor szignifikánsan alacsonyabb procedúraidővel. Orv. Hetil., 2016, 157(22), 849–854

A vadászat és vadgazdálkodás társadalmi megítélése Csongrád megyében

Nowadays, there is an increasing debate and negative campaign about the hunting and wildlife management first of all from outsiders, from incompetent people. It is interesting that a few decades ago hunters were honoured by the public, and they were envied by many people. The situation and the public opinion have changed for today. In the recent study we looked for answers to the following questions: 1. How the awareness formed in the different age groups of local population in Csongrád county? 2. Whether are they familiar with the hunters' tasks, responsibilities and the importance of it? Children in the age of primary and secondary school and adults were interviewed by questionnaires. Different questionnaires were compiled for every age group including questions for measuring the general awareness and special knowledge on the topic. The results of the survey could help in the development of knowledge and public opinion even in adult or childhood, and the reputation of hunters and wildlife managers maybe could restored

A vadászat és vadgazdálkodás társadalmi megítélése Csongrád megyében

Nowadays, there is an increasing debate and negative campaign about the hunting and wildlife management first of all from outsiders, from incompetent people. It is interesting that a few decades ago hunters were honoured by the public, and they were envied by many people. The situation and the public opinion have changed for today. In the recent study we looked for answers to the following questions: 1. How the awareness formed in the different age groups of local population in Csongrád county? 2. Whether are they familiar with the hunters' tasks, responsibilities and the importance of it? Children in the age of primary and secondary school and adults were interviewed by questionnaires. Different questionnaires were compiled for every age group including questions for measuring the general awareness and special knowledge on the topic. The results of the survey could help in the development of knowledge and public opinion even in adult or childhood, and the reputation of hunters and wildlife managers maybe could restored

Workstation Configuration and Process Planning for RLW Operations

The application of Remote Laser Welding (RLW) has become an attractive assembly technology in various branches of industry, as it offers higher efficiency at lower costs compared to traditional Resistance Spot Welding (RSW) when high volumes of sheet metal assemblies are to be produced. However, the introduction of RLW technology raises multiple new issues in designing the configuration, the layout, and the behavior of the assembly system. Since configuring an RLW workstation and planning the welding process are closely interrelated problems, a hierarchical decision process must be applied where configuration and planning go hand in hand. The paper presents a hierarchical workflow forworkstation configuration and process planning for RLW operations, and proposes methods for solving the decision problems related to each step of this workflow. A software toolbox is introduced that has been developed to facilitate a semi-Automatic, mixed-initiative workstation design and t o guide the expert user throughout the configuration, planning, programming, evaluation, and simulation of the RLW workstation. A case study from the automotive industry is presented, where the software tools developed are applied to configuring and planning the behavior of an RLW workstation that replaces RSW technology in assembling a car door

Cognitive dysfunction in autoimmune rheumatic diseases

L

Could successful cryoballoon ablation of paroxysmal atrial fibrillation prevent progressive left atrial remodeling?

<p>Abstract</p> <p>Background</p> <p>Radiofrequency catheter ablation of atrial fibrillation (AF) has been proved to be effective and to prevent progressive left atrial (LA) remodeling. Cryoballoon catheter ablation (CCA), using a different energy source, was developed to simplify the ablation procedure. Our hypothesis was that successful CCA can also prevent progressive LA remodeling.</p> <p>Methods</p> <p>36 patients selected for their first CCA because of nonvalvular paroxysmal AF had echocardiography before and 3, 6 and 12 months after CCA. LA diameters, volumes (LAV) and LA volume index (LAVI) were evaluated. LA function was assessed by: early diastolic velocities of the mitral annulus (Aa_sept, Aa_lat), LA filling fraction (LAFF), LA emptying fraction (LAEF) and the systolic fraction of pulmonary venous flow (PVSF). Detailed left ventricular diastolic function assessment was also performed.</p> <p>Results</p> <p>Excluding recurrences in the first 3-month blanking period, the clinical success rate was 64%. During one-year of follow-up, recurrent atrial arrhythmia was found in 21 patients (58%). In the recurrent group at 12 months after ablation, minimal LAV (38 ± 19 to 44 ± 20 ml; <it>p </it>< 0.05), maximal LAV (73 ± 23 to 81 ± 24 ml; <it>p </it>< 0.05), LAVI (35 ± 10 to 39 ± 11 ml/m²; <it>p </it>= 0.01) and the maximal LA longitudinal diameter (55 ± 5 to 59 ± 6 mm; <it>p </it>< 0.01) had all increased. PVSF (58 ± 9 to 50 ± 10%; <it>p </it>= 0.01) and LAFF (36 ± 7 to 33 ± 8%; <it>p </it>= 0.03) had decreased. In contrast, after successful cryoballoon ablation LA size had not increased and LA function had not declined. In the recurrent group LAEF was significantly lower at baseline and at follow-up visits.</p> <p>Conclusions</p> <p>In patients whose paroxysmal atrial fibrillation recurred within one year after cryoballoon catheter ablation left atrial size had increased and left atrial function had declined. In contrast, successful cryoballoon catheter ablation prevented progressive left atrial remodeling.</p