Catheter ablation or medical therapy to delay progression of atrial fibrillation : The randomized controlled atrial fibrillation progression trial (ATTEST)

Funding Information: This work was supported by Biosense Webster, Inc. Publisher Copyright: © 2020 The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.Aims: Delay of progression from paroxysmal to persistent atrial fibrillation (AF) is an important measure of long-term success of AF treatment. However, published data on the impact of catheter ablation on AF progression are limited. This study evaluates whether radiofrequency (RF) catheter ablation delays the progression of AF compared with antiarrhythmic drug (AAD) treatment using current AF management guidelines. Methods: This prospective, randomized, controlled, two-arm, open-label trial was conducted at 29 hospitals and medical centres across 13 countries. Patients were randomized 1: 1 to RF ablation or AAD treatment. The primary endpoint was the rate of persistent AF/atrial tachycardia (AT) at 3 years. Results: After early study termination following slow enrolment, 255 (79%) of the planned 322 patients were enrolled (RF ablation, n = 128, AAD, n = 127); 36% of patients in the RF ablation group and 41% in the AAD group completed 3 years of follow-up. For the primary endpoint, the Kaplan-Meier estimate of the rate of persistent AF/AT at 3 years was significantly lower with RF ablation [2.4% (95% confidence interval (CI), 0.6-9.4%)] than with AAD therapy [17.5% (95% CI, 10.7-27.9%); one-sided P = 0.0009]. Patients ≥65 years were ∼4 times more likely to progress to persistent AF/AT than patients <65 years, suggesting RF ablation can delay disease progression [hazard ratio: 3.87 (95% CI, 0.88-17.00); P = 0.0727]. Primary adverse events were reported for eight patients in the RF ablation group. Conclusions: Radiofrequency ablation is superior to guideline-directed AAD therapy in delaying the progression from paroxysmal to persistent AF.publishersversionPeer reviewe

Novel long-chain neurotoxins from Bungarus candidus distinguish the two binding sites in muscle-type nicotinic acetylcholine receptors

αδ-Bungarotoxins, a novel group of long-chain α-neurotoxins, manifest different affinity to two agonist/competitive antagonist binding sites of muscle-type nicotinic acetylcholine receptors (nAChRs), being more active at the interface of α–δ subunits. Three isoforms (αδ-BgTx-1–3) were identified in Malayan Krait (Bungarus candidus) from Thailand by genomic DNA analysis; two of them (αδ-BgTx-1 and 2) were isolated from its venom. The toxins comprise 73 amino acid residues and 5 disulfide bridges, being homologous to α-bungarotoxin (α-BgTx), a classical blocker of muscle-type and neuronal α7, α8, and α9α10 nAChRs. The toxicity of αδ-BgTx-1 (LD50 = 0.17–0.28 µg/g mouse, i.p. injection) is essentially as high as that of α-BgTx. In the chick biventer cervicis nerve–muscle preparation, αδ-BgTx-1 completely abolished acetylcholine response, but in contrast with the block by α-BgTx, acetylcholine response was fully reversible by washing. αδ-BgTxs, similar to α-BgTx, bind with high affinity to α7 and muscle-type nAChRs. However, the major difference of αδ-BgTxs from α-BgTx and other naturally occurring α-neurotoxins is that αδ-BgTxs discriminate the two binding sites in the Torpedo californica and mouse muscle nAChRs showing up to two orders of magnitude higher affinity for the α–δ site as compared with α–ε or α–γ binding site interfaces. Molecular modeling and analysis of the literature provided possible explanations for these differences in binding mode; one of the probable reasons being the lower content of positively charged residues in αδ-BgTxs. Thus, αδ-BgTxs are new tools for studies on nAChRs

Желудочковая экстрасистолия у детей

The article presents updated data on the problem of premature ventricular contractions in children based on the clinical guidelines of the Russian Society of Cardiology and the Union of Pediatricians of Russia for the diagnosis, treatment and management of pediatric patients with premature ventricular contraction. The issues of diagnosis and treatment based on the principles of evidence-based medicine as well as important aspects of prevention of exacerbations and follow-up have been clarified in detail. The criteria for assessing the quality of care for patients with premature ventricular contractions have been presented.CONFLICT OF INTEREST. Not declared.В статье изложены обновленные данные о проблеме желудочковых экстрасистолий у детей, основанные на клинических рекомендациях Ассоциации детских кардиологов России и Союза педиатров России по диагностике, лечению и ведению пациентов детского возраста с желудочковой экстрасистолией. Подробно освещены вопросы диагностики, лечения, основанные на принципах доказательной медицины, а также важные аспекты профилактики обострений болезни и диспансерного наблюдения. Отображены критерии оценки качества медицинской помощи пациентам с желудочковыми экстрасистолиями.Публикация является обновленным вариантом клинических рекомендаций Ассоциации детских кардиологов России и Союза педиатров России по диагностике, лечению и ведению пациентов детского возраста с желудочковой экстрасистолией, опубликованных на сайте https://medi.ru/klinicheskie-rekomendatsii/zheludochkovaya-ekstrasistoliya-u-detej_14366/Авторы подтверждают отсутствие конфликта интересов, который необходимо обнародовать

Electric dipole moments and the search for new physics

Static electric dipole moments of nondegenerate systems probe mass scales for physics beyond the Standard Model well beyond those reached directly at high energy colliders. Discrimination between different physics models, however, requires complementary searches in atomic-molecular-and-optical, nuclear and particle physics. In this report, we discuss the current status and prospects in the near future for a compelling suite of such experiments, along with developments needed in the encompassing theoretical framework.Comment: Contribution to Snowmass 2021; updated with community edits and endorsement

Phenological shifts of abiotic events, producers and consumers across a continent

Ongoing climate change can shift organism phenology in ways that vary depending on species, habitats and climate factors studied. To probe for large-scale patterns in associated phenological change, we use 70,709 observations from six decades of systematic monitoring across the former Union of Soviet Socialist Republics. Among 110 phenological events related to plants, birds, insects, amphibians and fungi, we find a mosaic of change, defying simple predictions of earlier springs, later autumns and stronger changes at higher latitudes and elevations. Site mean temperature emerged as a strong predictor of local phenology, but the magnitude and direction of change varied with trophic level and the relative timing of an event. Beyond temperature-associated variation, we uncover high variation among both sites and years, with some sites being characterized by disproportionately long seasons and others by short ones. Our findings emphasize concerns regarding ecosystem integrity and highlight the difficulty of predicting climate change outcomes. The authors use systematic monitoring across the former USSR to investigate phenological changes across taxa. The long-term mean temperature of a site emerged as a strong predictor of phenological change, with further imprints of trophic level, event timing, site, year and biotic interactions.Peer reviewe

Occurrence of Volatile and Semi-Volatile Organic Pollutants in the Russian Arctic Atmosphere: The International Siberian Shelf Study Expedition (ISSS-2020)

Environmental issues in the Arctic region are of primary importance due to the fragility of the Arctic ecosystem. Mainly persistent organic compounds are monitored in the region by nine stationary laboratories. Information on the volatile (VOC) and semi volatile (SVOC) organic priority pollutants is very limited, especially for the Russian Arctic. Air samples from 16 sites along the Russian Arctic coast from the White Sea to the East Siberian Sea were collected on sorption tubes packed with Tenax, Carbograph, and Carboxen sorbents with different selectivity for a wide range of VOCs and SVOCs in 2020 within the framework of the International Siberian Shelf Study Expedition on the research vessel Akademik Keldysh. Thermal desorption gas chromatography–high-resolution mass spectrometry with Orbitrap was used for the analysis. Eighty-six VOCs and SVOCs were detected in the air samples at ng/m3 levels. The number of quantified compounds varied from 26 to 66 per sample. Benzoic acid was the major constituent, followed by BTEX, phenol, chloroform, bis(2-ethylhexyl) phthalate, and carbon tetrachloride. The study allowed for obtaining the first ever data on the presence of 138 priority pollutants in the air of Russian Arctic, whereas the thorough assessment of their possible sources will be the aim of a next investigation

Transversal Stiffness and Young's Modulus of Single Fibers from Rat Soleus Muscle Probed by Atomic Force Microscopy

The structural integrity of striated muscle is determined by extra-sarcomere cytoskeleton that includes structures that connect the Z-disks and M-bands of a sarcomere to sarcomeres of neighbor myofibrils or to sarcolemma. Mechanical properties of these structures are not well characterized. The surface structure and transversal stiffness of single fibers from soleus muscle of the rat were studied with atomic force microscopy in liquid. We identified surface regions that correspond to projections of the Z-disks, M-bands, and structures between them. Transversal stiffness of the fibers was measured in each of these three regions. The stiffness was higher in the Z-disk regions, minimal between the Z-disks and the M-bands, and intermediate in the M-band regions. The stiffness increased twofold when relaxed fibers were maximally activated with calcium and threefold when they were transferred to rigor (ATP-free) solution. Transversal stiffness of fibers heavily treated with Triton X-100 was about twice higher than that of the permeabilized ones, however, its regional difference and the dependence on physiological state of the fiber remained the same. The data may be useful for understanding mechanics of muscle fibers when it is subjected to both axial and transversal strain and stress

Evidence of Specialized Tissue in Human Interatrial Septum: Histological, Immunohistochemical and Ultrastructural Findings

<div><p>Background</p><p>There is a paucity of information on structural organization of muscular bundles in the interatrial septum (IAS). The aim was to investigate histologic and ultrastructural organization of muscular bundles in human IAS, including fossa ovalis (FO) and flap valve.</p><p>Methods</p><p>Macroscopic and light microscopy evaluations of IAS were performed from postmortem studies of 40 patients. Twenty three IAS specimens underwent serial transverse sectioning, and 17 - longitudinal sectioning. The transverse sections from 10 patients were immunolabeled for HCN4, Caveolin3 and Connexin43. IAS specimens from 6 other patients underwent electron microscopy.</p><p>Results</p><p>In all IAS specimens sections the FO, its rims and the flap valve had muscle fibers consisting of working cardiac myocytes. Besides the typical cardiomyocytes there were unusual cells: tortuous and horseshoe-shaped intertangled myocytes, small and large rounded myocytes with pale cytoplasm. The cells were aggregated in a definite structure in 38 (95%) cases, which was surrounded by fibro-fatty tissue. The height of the structure on transverse sections positively correlated with age (P = 0.03) and AF history (P = 0.045). Immunohistochemistry showed positive staining of the cells for HCN4 and Caveolin3. Electron microscopy identified cells with characteristics similar to electrical conduction cells.</p><p>Conclusions</p><p>Specialized conduction cells in human IAS have been identified, specifically in the FO and its flap valve. The cells are aggregated in a structure, which is surrounded by fibrous and fatty tissue. Further investigations are warranted to explore electrophysiological characteristics of this structure.</p></div