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This randomized study aims to compare the left atrial (LA) lesion size, function, and tissue damage following pulmonary vein isolation (PVI) by high-power short-duration (HPSD) radiofrequency (RF) and second-generation cryoballoon (CB2) ablation. We enrolled 40 patients with paroxysmal atrial fibrillation who underwent PVI by HPSD RF (n = 21) or CB2 (n = 19). Every patient underwent LA CT angiography and transthoracic echocardiography (TTE) to assess the LA anatomy and function. Biomarker levels (hs-cTnT, hs-CRP, LDH) were compared pre- and post-procedurally. Pre- and post-ablation high-density mapping (HDM) was performed. The isolation area was defined under 0.2 mV bipolar voltage (low voltage area, LVA). We calculated the post-PVI LVA/LA surface ratio using LA CT-HDM merge images. At 3-month follow-up, TTE was performed to assess the changes in LA function. Post-ablation hs-cTnT level was significantly higher in the RF group (RF: 1249 ± 469 ng/L, CB2: 995 ± 280 ng/L, p = 0.024). Post-PVI hs-CRP (RF: 9.53 ± 10.30 mg/L, CB2: 12.36 ± 5.76 mg/L, p = 0.034) and LDH levels (RF: 349.9 ± 65.6 U/L, CB2: 451.6 ± 91.3 U/L, p < 0.001) were significantly higher following CB2 ablation. Post-PVI LVA/LA surface ratios were 8.37 ± 6.42% in the RF group and 13.58 ± 8.92% in the CB2 group (p = 0.022). LA function did not change significantly after the PVI procedure. Our data indicate that second-generation cryoballoon ablation produces a significantly larger LA lesion size compared to “point-by-point” HPSD radiofrequency. Both techniques preserve LA function. The myocardial component of tissue loss appears to be higher using HPSD radiofrequency ablation, with less collateral damage.

Antibiotics that inhibit multiple bacterial targets offer a promising therapeutic strategy against resistance evolution, but developing such antibiotics is challenging. Here we demonstrate that a rational design of balanced multitargeting antibiotics is feasible by using a medicinal chemistry workflow. The resultant lead compounds, ULD1 and ULD2, belonging to a novel chemical class, almost equipotently inhibit bacterial DNA gyrase and topoisomerase IV complexes and interact with multiple evolutionary conserved amino acids in the ATP-binding pockets of their target proteins. ULD1 and ULD2 are excellently potent against a broad range of gram-positive bacteria. Notably, the efficacy of these compounds was tested against a broad panel of multidrug-resistant Staphylococcus aureus clinical strains. Antibiotics with clinical relevance against staphylococcal infections fail to inhibit a significant fraction of these isolates, whereas both ULD1 and ULD2 inhibit all of them (minimum inhibitory concentration [MIC] ≤1 μg/mL). Resistance mutations against these compounds are rare, have limited impact on compound susceptibility, and substantially reduce bacterial growth. Based on their efficacy and lack of toxicity demonstrated in murine infection models, these compounds could translate into new therapies against multidrug-resistant bacterial infections.

Acute pancreatitis (AP) is often accompanied by alterations in the acid-base balance, but how blood pH influences the outcome of AP is largely unknown. We studied the association between blood pH and the outcome of AP with meta-analysis of clinical trials, and aimed to discover the causative relationship between blood pH and AP in animal models. PubMed, EMBASE, and Cochrane Controlled Trials Registry databases were searched from inception to January 2017. Human studies reporting systemic pH status and outcomes (mortality rate, severity scores, and length of hospital stay) of patient groups with AP were included in the analyses. We developed a new mouse model of chronic metabolic acidosis (MA) and induced mild or severe AP in the mice. Besides laboratory blood testing, the extent of pancreatic edema, necrosis, and leukocyte infiltration were assessed in tissue sections of the mice. Thirteen studies reported sufficient data in patient groups with AP (n = 2,311). Meta-analysis revealed markedly higher mortality, elevated severity scores, and longer hospital stay in AP patients with lower blood pH or base excess (P < 0.001 for all studied outcomes). Meta-regression analysis showed significant negative correlation between blood pH and mortality in severe AP. In our mouse model, pre-existing MA deteriorated the pancreatic damage in mild and severe AP and, vice versa, severe AP further decreased the blood pH of mice with MA. In conclusion, MA worsens the outcome of AP, while severe AP augments the decrease of blood pH. The discovery of this vicious metabolic cycle opens up new therapeutic possibilities in AP.

In this study, the sporting activity of Hungarian school pupils is investigated with a focus on regional differences. The objective of the paper is to answer the following questions: Are there regional differences in pupils’ sporting activity, and, if yes, what is their relationship with the socio-cultural background of the pupils and the infrastructural and staffing conditions of schools? Has the 2012 introduction of daily physical education had a different effect on pupils’ leisure-time sporting activity in disadvantaged and affluent regions? Can the trends in the sporting activity of pupils be characterized as convergent or divergent since the introduction of daily physical education? The paper is based on an extensive study that relies on the most comprehensive database on physical education in schools, the National Assessment of Basic Competencies (NABC). The present study statistically analyzed eighth-grade pupil and school data from the 2010 and 2014 NABC. The results present the regional differences in pupils’ participation in sporting activity, their recent modification, and the main reasons behind the changes. In conclusion, the authors state that social, economic, and cultural inequalities are not clearly reflected in the sporting activity of students; however, certain data still call attention to the need to examine regional differences.

BackgroundPopulation‐based studies suggest that genetic factors contribute to sudden cardiac death (SCD). Methods and ResultsIn the first part of the present study (Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Ventricular Tachy‐arrhythmia in ICD Patients [DISCOVERY] trial) Cox regression was done to determine if 7 single‐nucleotide polymorphisms (SNPs) in 3 genes coding G‐protein subunits (GNB3, GNAQ, GNAS) were associated with ventricular tachyarrhythmia (VT) in 1145 patients receiving an implantable cardioverter‐defibrillator (ICD). In the second part of the study, SNPs significantly associated with VT were further investigated in 1335 subjects from the Oregon SUDS, a community‐based study analyzing causes of SCD. In the DISCOVERY trial, genotypes of 2 SNPs in the GNAS gene were nominally significant in the prospective screening and significantly associated with VT when viewed as recessive traits in post hoc analyses (TT vs CC/CT in c.393C>T: HR 1.42 [CI 1.11‐1.80], P=0.005; TT vs CC/CT in c.2273C>T: HR 1.57 [CI 1.18‐2.09], P=0.002). TT genotype in either SNP was associated with a HR of 1.58 (CI 1.26‐1.99) (P=0.0001). In the Oregon SUDS cohort significant evidence for association with SCD was observed for GNAS c.393C>T under the additive (P=0.039, OR=1.21 [CI 1.05‐1.45]) and recessive (P=0.01, OR=1.52 [CI 1.10‐2.13]) genetic models. ConclusionsGNAS harbors 2 SNPs that were associated with an increased risk for VT in ICD patients, of which 1 was successfully replicated in a community‐based population of SCD cases. To the best of our knowledge, this is the first example of a gene variant identified by ICD VT monitoring as a surrogate parameter for SCD and also confirmed in the general population. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00478933.

What happens when a person accepts a new leadership position only to discover that the team they are charged with overseeing is in disarray? The transition to a new leader often causes stress between and among employees. Employee satisfaction and productivity may be lacking, teamwork may be nonexistent, and change may be met with resistance. This article offers some pointers on how leaders who "start off on the wrong foot" can turn the situation around and produce the desired results for the team and the institutiion.

Taking a new job can be stressful, chaotic and trying. This is especially true if your new position is that of a leadership role in which you are responsible for others' actions. However, there are some steps you can take that will help you ease into your new role and create a cohesive team working toward the same goals and outcomes.

Background: One of the crucial points during in most approaches developed for ablation of atrial fibrillation (AF) is the ability to identify the pulmonary vein (PVs) and to accurately locate their ostia. Objectives: The purpose of this case series was to investigate a simplified method for fusion of the multislice computer tomography (CT) derived 3D dataset with the electroanatomical map in order to facilitate the mapping procedure. Methods: In 5 consecutive patients (4 male) referred for catheter ablation of symptomatic drug-refractory paroxysmal atrial fibrillation contrast enhanced computer tomography was performed before the procedure and imported into an electroanatomical mapping system (Carto XP) using CartoMerge Image Integration Module. During the procedure a multipolar mapping catheter (Quick Star DS, Biosense Webster, Diamond Bar, CA, USA) was introduced to the coronary sinus (CS) to align the CSCT shell to the proper position. The CS potentials provided information to identify the ostium of the CS to achieve a more accurate fusion of the images. No mapping points were taken in the left atrium. The feasibility of the method was characterized by the distance of mapping points. Mapping, registration and outcome data were compared with a cohort of patients undergoing MRI image integration. Result: The mean distance between the mapping points taken in the CS by the Quick Star catheter and the CS CT surface was suitable (mean±SD, 1.4±0.3 mm). Full electrical isolation of the pulmonary veins could be achieved in all patients. The mean procedure and fluoroscopy time were 39 ± 22 and 134 ±38 min respectively, significantly decreased as compared to the MRI cohort. Conclusions: Highly accurate CT image and the electroanatomical map (EAM) fusion can be obtained by the Carto 3D electromanatomical mapping system using CS as the key anatomical structure for registration. Using this technique the mapping time of the left atrium can be reduced.

Alternative methods are necessary for cardiac resynchronization therapy when coronary sinus lead implantation fails. We aim to describe a fundamentally new approach using transapical implantation of an active fixation endocardial pacing lead. This technique is based on direct puncture of the left ventricular apex using the standard Seldinger technique. The tip of the lead is positioned with intracavital navigation under fluoroscopy. This method offers advantages for cardiac resynchronization because it is minimally invasive, provides endocardial pacing, and does not involve the mitral valve. [Copyright &y& Elsevier]