Na+ channel function, regulation, structure, trafficking and sequestration.

This paper is the second of a series of three reviews published in this issue resulting from the University of California Davis Cardiovascular Symposium 2014: Systems approach to understanding cardiac excitation-contraction coupling and arrhythmias: Na(+) channel and Na(+) transport. The goal of the symposium was to bring together experts in the field to discuss points of consensus and controversy on the topic of sodium in the heart. The present review focuses on Na(+) channel function and regulation, Na(+) channel structure and function, and Na(+) channel trafficking, sequestration and complexing.

Unmasking the dormant pulmonary vein conduction with adenosine administration after pulmonary vein isolation with laser energy.

Aims: The isolation of the pulmonary veins (PVs) is the mainstay of atrial fibrillation (AF) ablation, which with current ablation techniques can be achieved in almost all cases. Reconnection of PVs constitutes the most frequent cause of AF recurrence. Visually guided laser balloon ablation (VGLA) is a novel system with very high rate of persistence of pulmonary vein isolation (PVI) three months after the first procedure shown in preclinical and clinical studies.

Deletion of the Sm1 encoding motif in the lsm gene results in distinct changes in the transcriptome and enhanced swarming activity of Haloferax cells.

Members of the Sm protein family are important for the cellular RNA metabolism in all three domains of life. The family includes archaeal and eukaryotic Lsm proteins, eukaryotic Sm proteins and archaeal and bacterial Hfq proteins. While several studies concerning the bacterial and eukaryotic family members have been published, little is known about the archaeal Lsm proteins.

Biology-oriented synthesis of a withanolide-inspired compound collection reveals novel modulators of hedgehog signaling.

Biology-oriented synthesis employs the structural information encoded in complex natural products to guide the synthesis of compound collections enriched in bioactivity. The trans-hydrindane dehydro-δ-lactone motif defines the characteristic scaffold of the steroid-like withanolides, a plant-derived natural product class with a diverse pattern of bioactivity. A withanolide-inspired compound collection was synthesized by making use of three key intermediates that contain this characteristic framework derivatized with different reactive functional groups.

Nonsinusoidal current-phase relationship in Josephson junctions from the 3D topological insulator HgTe.

We use superconducting quantum interference device microscopy to characterize the current-phase relation (CPR) of Josephson junctions from the three-dimensional topological insulator HgTe (3D HgTe). We find clear skewness in the CPRs of HgTe junctions ranging in length from 200 to 600 nm. The skewness indicates that the Josephson current is predominantly carried by Andreev bound states with high transmittance, and the fact that the skewness persists in junctions that are longer than the mean free path suggests that the effect may be related to the helical nature of the Andreev bound states in the surface of HgTe.

The Adaptive Immune System of Haloferax volcanii.

To fight off invading genetic elements, prokaryotes have developed an elaborate defence system that is both adaptable and heritable-the CRISPR-Cas system (CRISPR is short for: clustered regularly interspaced short palindromic repeats and Cas: CRISPR associated). Comprised of proteins and multiple small RNAs, this prokaryotic defence system is present in 90% of archaeal and 40% of bacterial species, and enables foreign intruders to be eliminated in a sequence-specific manner. There are three major types (I-III) and at least 14 subtypes of this system, with only some of the subtypes having been analysed in detail, and many aspects of the defence reaction remaining to be elucidated.

Beryllium increases the CD14(dim)CD16+ subset in the lung of chronic beryllium disease.

CD14dimCD16+ and CD14brightCD16+ cells, which compose a minor population of monocytes in human peripheral blood mononuclear cells (PBMC), have been implicated in several inflammatory diseases. The aim of this study was to investigate whether this phenotype was present as a subset of lung infiltrative alveolar macrophages (AMs) in the granulomatous lung disease, chronic beryllium disease (CBD). The monocytes subsets was determined from PBMC cells and bronchoalveolar lavage (BAL) cells from CBD, beryllium sensitized Non-smoker (BeS-NS) and healthy subjects (HS) using flow cytometry.

Hospital use of systemic antifungal drugs: a multi-center surveillance update from Germany.

Background: The consumption of antifungal agents increased over the last decade, resulting in the development of resistant organisms and causing a significant pharmaco economic burden. Antifungal drugs are widely used for the treatment of systemic fungal infections and high-risk patients, especially with severe hematological or oncological conditions. Up to date, there are no reliable and systematically reported data on the consumption of antifungal substances on a nationwide level available.

Single Institution Experience With Transcatheter Valve-in-Valve Implantation Emphasizing Strategies for Coronary Protection.

Background: Transcatheter valve-in-valve (VIV) implantation evolved as a therapeutic alternative, despite an increased risk of coronary obstruction in comparison with a regular transcatheter aortic valve implantation (TAVI). We report a comprehensive single-institution experience emphasizing strategies to reduce the risk of myocardial ischemia.

Methods: Since 2009, 639 patients underwent a TAVI procedure in our institution.

Targets for therapy in sarcomeric cardiomyopathies.

To date, no compounds or interventions exist that treat or prevent sarcomeric cardiomyopathies. Established therapies currently improve the outcome, but novel therapies may be able to more fundamentally affect the disease process and course. Investigations of the pathomechanisms are generating molecular insights that can be useful for the design of novel specific drugs suitable for clinical use.

Epigenetic balance of aberrant Rasal1 promoter methylation and hydroxymethylation regulates cardiac fibrosis.

Aims: Methylation of CpG island promoters is a prototypical epigenetic mechanism to stably control gene expression. The aim of this study was to elucidate the contribution of aberrant promoter DNA methylation in pathological endothelial to mesenchymal transition (EndMT) and subsequent cardiac fibrosis.

Methods And Results: In human coronary endothelial cells, TGFβ1 causes aberrant methylation of RASAL1 promoter, increased Ras-GTP activity, and EndMT.

Ranolazine in the treatment of atrial fibrillation: Results of the dose-ranging RAFFAELLO (Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion) study.

Background: Currently available antiarrhythmic agents for the treatment of atrial fibrillation (AF) have important limitations, leaving an unmet need for safe and effective therapy. Ranolazine is an approved antianginal agent with a favorable safety profile and electrophysiologic properties suggesting a potential role in the treatment of AF.

Objective: The purpose of this study was to assess the safety and efficacy of ranolazine in the prevention of AF recurrence after successful electrical cardioversion and to ascertain the most appropriate dose of this agent.

Granulocytes impose a tight bottleneck upon the gut luminal pathogen population during Salmonella typhimurium colitis.

Topological, chemical and immunological barriers are thought to limit infection by enteropathogenic bacteria. However, in many cases these barriers and their consequences for the infection process remain incompletely understood. Here, we employed a mouse model for Salmonella colitis and a mixed inoculum approach to identify barriers limiting the gut luminal pathogen population.

An active immune defense with a minimal CRISPR (clustered regularly interspaced short palindromic repeats) RNA and without the Cas6 protein.

The prokaryotic immune system CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated) is a defense system that protects prokaryotes against foreign DNA. The short CRISPR RNAs (crRNAs) are central components of this immune system. In CRISPR-Cas systems type I and III, crRNAs are generated by the endonuclease Cas6.

The German CPU Registry: Dyspnea independently predicts negative short-term outcome in patients admitted to German Chest Pain Units.

Background: While dyspnea is a common symptom in patients admitted to Chest Pain Units (CPUs) little is known about the impact of dyspnea on their outcome. The purpose of this study was to evaluate the impact of dyspnea on the short-term outcome of CPU patients.

Methods: We analyzed data from a total of 9169 patients admitted to one of the 38 participating CPUs in this registry between December 2008 and January 2013.

Guideline-adherence and perspectives in the acute management of unstable angina - Initial results from the German chest pain unit registry.

Background: We investigated the current management of unstable angina pectoris (UAP) in certified chest pain units (CPUs) in Germany and focused on the European Society of Cardiology (ESC) guideline-adherence in the timing of invasive strategies or choice of conservative treatment options. More specifically, we analyzed differences in clinical outcome with respect to guideline-adherence.

Method: Prospective data from 1400 UAP patients were collected.

Structural analyses of the CRISPR protein Csc2 reveal the RNA-binding interface of the type I-D Cas7 family.

Upon pathogen invasion, bacteria and archaea activate an RNA-interference-like mechanism termed CRISPR (clustered regularly interspaced short palindromic repeats). A large family of Cas (CRISPR-associated) proteins mediates the different stages of this sophisticated immune response. Bioinformatic studies have classified the Cas proteins into families, according to their sequences and respective functions.

p38 Mitogen-Activated Protein Kinase in beryllium-induced dendritic cell activation.

Dendritic cells (DC) play a role in the regulation of immune responses to haptens, which in turn impact DC maturation. Whether beryllium (Be) is able to induce DC maturation and if this occurs via the MAPK pathway is not known. Primary monocyte-derived DCs (moDCs) models were generated from Be non-exposed healthy volunteers as a non-sensitized cell model, while PBMCs from BeS (Be sensitized) and CBD (chronic beryllium disease) were used as disease models.

An official American Thoracic Society statement: diagnosis and management of beryllium sensitivity and chronic beryllium disease.

Rationale: Beryllium continues to have a wide range of industrial applications. Exposure to beryllium can lead to sensitization (BeS) and chronic beryllium disease (CBD).

Objectives: The purpose of this statement is to increase awareness and knowledge about beryllium exposure, BeS, and CBD.

Salmonella Typhimurium strain ATCC14028 requires H2-hydrogenases for growth in the gut, but not at systemic sites.

Salmonella enterica is a common cause of diarrhea. For eliciting disease, the pathogen has to colonize the gut lumen, a site colonized by the microbiota. This process/initial stage is incompletely understood.

Efficacy of mycophenolate mofetil in sarcoidosis.

Background: Immunosuppressive (IS) therapy is indicated to treat progressive sarcoidosis, but randomized controlled trials to guide physicians in the use of steroid sparing agents are lacking. The aim of this retrospective study was to examine the role of mycophenolate mofetil (MMF) as an alternative therapy in the treatment of sarcoidosis.

Methods: A retrospective chart review of all patients who had been prescribed MMF between January 2008 and October 2011 was conducted.

[Extracorporeal pulmonary support procedures in intensive care medicine 2014].

Background: In recent years a rapid expansion of extracorporeal devices for support of severe lung failure has been witnessed. Systems for veno-venous extracorporeal membrane oxygenation (VV-ECMO) or for extracorporeal carbon dioxide elimination are distinguished depending on the indications.

Objectives: The state of the art of extracorporeal lung support is presented with an overview of the different systems, the indications, efficiency and potential side effects.

Case series of volar juvenile xanthogranuloma: clinical observation of a peripheral rim of hyperkeratosis.

Juvenile xanthogranuloma is a benign histiocytic tumor predominantly occurring in children as yellowish papules on the head and trunk. Presentations on the volar surfaces are rare and may cause diagnostic confusion with pyogenic granuloma, eccrine poroma and digital fibrokeratoma. We report two patients with unusual presentations of solitary juvenile xanthogranuloma on the palm or sole.