Heart Rate Variability and Atria Function in Children at Late Follow-Up Evaluation After Atrioventricular Node Slow-Pathway Radiofrequency Ablation

This study was designed to assess the changes in the conductive system, autonomic dysfunction, and global and regional function of the atria and ventricles in children late after slow-pathway radiofrequency ablation (RFA). The study enrolled 22 children, who has successfully undergone RFA 2 to 5 years previously (RFA group) and 20 healthy children (control group). Electrophysiologic study was performed for the RFA group. Holter monitoring and echocardiography were performed for all the children. At a late follow-up assessment, the RFA children were free of paroxysms, whereas 8 of the 22 children (36%) reported transient palpitations. Both mean and maximal heart rates (HR) were significantly increased, whereas indices of HR variability (% of succesive normal sinus RR intervals exceeding 50 ms [pNN50], root mean square of the succesive normal sinus RR interval difference [rMSSD], high-frequency component [HFC]) were significantly decreased in the RFA group compared with preablation and control data. Left atrial (LA) and right atrial (RA) volumes were significantly higher, and atria deformation indices were significantly lower in the RFA group. Correlations were found between the mean HR and the volumes of LA (r = 0.477; p < 0.001) and RA (r = 0.512; p < 0.001). A negative correlation between the maximal LA volume and the longitudinal strain rate (SR) during relaxation (r = –0.476; p = 0.03) and a positive correlation between the minimal LA volume and both longitudinal SR (r = 0.361; p = 0.03) and strain (ε) (r = 0.375; p = 0.024) during contraction were shown. These data suggest a possible link between atrial dysfunction and the hyperadrenergic state after RFA

Genetic Dissection of Acute Ethanol Responsive Gene Networks in Prefrontal Cortex: Functional and Mechanistic Implications

Background Individual differences in initial sensitivity to ethanol are strongly related to the heritable risk of alcoholism in humans. To elucidate key molecular networks that modulate ethanol sensitivity we performed the first systems genetics analysis of ethanol-responsive gene expression in brain regions of the mesocorticolimbic reward circuit (prefrontal cortex, nucleus accumbens, and ventral midbrain) across a highly diverse family of 27 isogenic mouse strains (BXD panel) before and after treatment with ethanol. Results Acute ethanol altered the expression of ~2,750 genes in one or more regions and 400 transcripts were jointly modulated in all three. Ethanol-responsive gene networks were extracted with a powerful graph theoretical method that efficiently summarized ethanol\u27s effects. These networks correlated with acute behavioral responses to ethanol and other drugs of abuse. As predicted, networks were heavily populated by genes controlling synaptic transmission and neuroplasticity. Several of the most densely interconnected network hubs, including Kcnma1 and Gsk3β, are known to influence behavioral or physiological responses to ethanol, validating our overall approach. Other major hub genes like Grm3, Pten and Nrg3 represent novel targets of ethanol effects. Networks were under strong genetic control by variants that we mapped to a small number of chromosomal loci. Using a novel combination of genetic, bioinformatic and network-based approaches, we identified high priority cis-regulatory candidate genes, including Scn1b,Gria1, Sncb and Nell2. Conclusions The ethanol-responsive gene networks identified here represent a previously uncharacterized intermediate phenotype between DNA variation and ethanol sensitivity in mice. Networks involved in synaptic transmission were strongly regulated by ethanol and could contribute to behavioral plasticity seen with chronic ethanol. Our novel finding that hub genes and a small number of loci exert major influence over the ethanol response of gene networks could have important implications for future studies regarding the mechanisms and treatment of alcohol use disorders

Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support

Surgical management of tetralogy of Fallot (TOF) results in anatomic and functional abnormalities in the majority of patients. Although right ventricular volume load due to severe pulmonary regurgitation can be tolerated for many years, there is now evidence that the compensatory mechanisms of the right ventricular myocardium ultimately fail and that if the volume load is not eliminated or reduced by pulmonary valve replacement the dysfunction might be irreversible. Cardiovascular magnetic resonance (CMR) has evolved during the last 2 decades as the reference standard imaging modality to assess the anatomic and functional sequelae in patients with repaired TOF. This article reviews the pathophysiology of chronic right ventricular volume load after TOF repair and the risks and benefits of pulmonary valve replacement. The CMR techniques used to comprehensively evaluate the patient with repaired TOF are reviewed and the role of CMR in supporting clinical decisions regarding pulmonary valve replacement is discussed

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research