Chronic beta-adrenoceptor blockade and human atrial cell electrophysiology: evidence of pharmacological remodelling

<b>Objective:</b> Chronic beta-adrenoceptor antagonist (β-blocker) treatment reduces the incidence of reversion to AF in patients, possibly via an adaptive myocardial response. However, the underlying electrophysiological mechanisms are presently unclear. We aimed to investigate electrophysiological changes in human atrial cells associated with chronic treatment with β-blockers and other cardiovascular-acting drugs. <b>Methods:</b> Myocytes were isolated enzymatically from the right atrial appendage of 40 consenting patients who were in sinus rhythm. The cellular action potential duration (APD), effective refractory period (ERP), L-type Ca<sup>2+</sup> current (<i>I</i><sub>CaL</sub>), transient (<i>I</i><sub>TO</sub>) and sustained (<i>I</i><sub>KSUS</sub>) outward K<sup>+</sup> currents, and input resistance (<i>R</i><sub>i</sub>) were recorded using the whole cell patch clamp. Drug treatments and clinical characteristics were compared with electrophysiological measurements using simple and multiple regression analyses. P<0.05 was taken as statistically significant. <b>Results:</b> In atrial cells from patients treated chronically with β-blockers, the APD<sub>90</sub> and ERP (75 beats/min stimulation) were significantly longer, at 213±11 and 233±11 ms, respectively (<i>n</i> = 15 patients), than in cells from non-β-blocked patients, at 176±12 and 184±12 ms (n = 11). These cells also displayed a significantly reduced action potential phase 1 velocity (22±3 vs. 34±3 V/s). Chronic β-blockade was also associated with a significant reduction in the heart rate (58±3 vs. 69±5 beats/min) and in the density of ITO (8.7±1.3 vs. 13.7±2.1 pA/pF), an increase in the Ri (214±24 vs. 132±14 MΩ), but no significant change in <i>I</i><sub>CaL</sub> or <i>I</i><sub>KSUS</sub>. The <i>I</i><sub>TO</sub> blocker 4-aminopyridine largely mimicked the changes in phase 1 and ERP associated with chronic β-blockade, in cells from non-β-blocked patients. Chronic treatment of patients with calcium channel blockers or angiotensin converting enzyme inhibitors (<i>n</i> = 11–13 patients) was not associated with any significant changes in atrial cell electrophysiology. <b>Conclusion:</b> The observed atrial cellular electrophysiological changes associated with chronic β-blockade are consistent with a long-term adaptive response, a type of ‘pharmacological remodelling’, and provide mechanistic evidence supportive of the anti-arrhythmic actions of β-blockade

Mining semantic data, user generated contents, and contextual information for cross-domain recommendation

Proceedings of 21th International Conference, UMAP 2013, Rome, Italy, June 10-14, 2013The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-38844-6_42Cross-domain recommender systems suggest items in a target domain by exploiting user preferences and/or domain knowledge available in a source domain. In this thesis we aim to develop a framework for cross-domain recommendation capable of mining heterogeneous sources of information such as semantically annotated data, user generated contents, and contextual signals. For this purpose, we investigate a number of approaches to extract, process, and integrate knowledge for linking distinct domains, and various models that exploit such knowledge for making effective recommendations across domains

Atrial cellular electrophysiological changes in patients with ventricular dysfunction may predispose to AF

<b>Background:</b> Left ventricular systolic dysfunction (LVSD) is a risk factor for atrial fibrillation (AF), but the atrial cellular electrophysiological mechanisms in humans are unclear. Objective This study sought to investigate whether LVSD in patients who are in sinus rhythm (SR) is associated with atrial cellular electrophysiological changes that could predispose to AF. <b>Methods:</b> Right atrial myocytes were obtained from 214 consenting patients in SR who were undergoing cardiac surgery. Action potentials or ion currents were measured using the whole-cell-patch clamp technique. <b>Results:</b> The presence of moderate or severe LVSD was associated with a shortened atrial cellular effective refractory period (ERP) (209 ± 8 ms; 52 cells, 18 patients vs 233 ± 7 ms; 134 cells, 49 patients; P <0.05); confirmed by multiple linear regression analysis. The left ventricular ejection fraction (LVEF) was markedly lower in patients with moderate or severe LVSD (36% ± 4%, n = 15) than in those without LVSD (62% ± 2%, n = 31; P <0.05). In cells from patients with LVEF ≤ 45%, the ERP and action potential duration at 90% repolarization were shorter than in those from patients with LVEF > 45%, by 24% and 18%, respectively. The LVEF and ERP were positively correlated (r = 0.65, P <0.05). The L-type calcium ion current, inward rectifier potassium ion current, and sustained outward ion current were unaffected by LVSD. The transient outward potassium ion current was decreased by 34%, with a positive shift in its activation voltage, and no change in its decay kinetics. <b>Conclusion:</b> LVSD in patients in SR is independently associated with a shortening of the atrial cellular ERP, which may be expected to contribute to a predisposition to AF

Bioremediation and biovalorisation of olive-mill wastes

Olive-mill wastes are produced by the industry of olive oil production, which is a very important economic activity, particularly for Spain, Italy and Greece, leading to a large environmental problem of current concern in the Mediterranean basin. There is as yet no accepted treatment method for all the wastes generated during olive oil production, mainly due to technical and economical limitations but also the scattered nature of olive mills across the Mediterranean basin. The production of virgin olive oil is expanding worldwide, which will lead to even larger amounts of olive-mill waste, unless new treatment and valorisation technologies are devised. These are encouraged by the trend of current environmental policies, which favour protocols that include valorisation of the waste. This makes biological treatments of particular interest. Thus, research into different biodegradation options for olive-mill wastes and the development of new bioremediation technologies and/or strategies, as well as the valorisation of microbial biotechnology, are all currently needed. This review, whilst presenting a general overview, focus critically on the most significant recent advances in the various types of biological treatments, the bioremediation technology most commonly applied and the valorisation options, which together will form the pillar for future developments within this fiel

Evidence for global cooling in the Late Cretaceous.

The Late Cretaceous ‘greenhouse’ world witnessed a transition from one of the warmest climates of the past 140 million years to cooler conditions, yet still without significant continental ice. Low-latitude sea surface temperature (SST) records are a vital piece of evidence required to unravel the cause of Late Cretaceous cooling, but high-quality data remain illusive. Here, using an organic geochemical palaeothermometer (TEX86), we present a record of SSTs for the Campanian–Maastrichtian interval (~83–66¿Ma) from hemipelagic sediments deposited on the western North Atlantic shelf. Our record reveals that the North Atlantic at 35¿°N was relatively warm in the earliest Campanian, with maximum SSTs of ~35¿°C, but experienced significant cooling (~7¿°C) after this to <~28¿°C during the Maastrichtian. The overall stratigraphic trend is remarkably similar to records of high-latitude SSTs and bottom-water temperatures, suggesting that the cooling pattern was global rather than regional and, therefore, driven predominantly by declining atmospheric pCO2 levels

Herbivorous turtle ants obtain essential nutrients from a conserved nitrogen-recycling gut microbiome.

Nitrogen acquisition is a major challenge for herbivorous animals, and the repeated origins of herbivory across the ants have raised expectations that nutritional symbionts have shaped their diversification. Direct evidence for N provisioning by internally housed symbionts is rare in animals; among the ants, it has been documented for just one lineage. In this study we dissect functional contributions by bacteria from a conserved, multi-partite gut symbiosis in herbivorous Cephalotes ants through in vivo experiments, metagenomics, and in vitro assays. Gut bacteria recycle urea, and likely uric acid, using recycled N to synthesize essential amino acids that are acquired by hosts in substantial quantities. Specialized core symbionts of 17 studied Cephalotes species encode the pathways directing these activities, and several recycle N in vitro. These findings point to a highly efficient N economy, and a nutritional mutualism preserved for millions of years through the derived behaviors and gut anatomy of Cephalotes ants