NaV1.5 and interacting proteins in human arrhythmogenic cardiomyopathy

Evaluation of: Noorman M, Hakim S, Kessler E et al. Remodeling of the cardiac sodium channel, connexin43, and plakoglobin at the intercalated disk in patients with arrhythmogenic cardiomyopathy. Heart Rhythm 10(3), 412-419 (2013). Arrhythmogenic cardiomyopathy (AC) is a heart muscle disease characterized by a progressive replacement of the ventricular myocardium with adipose and fibrous tissue. This disease is often associated with mutations in genes encoding desmosomal proteins in the majority of patients. Based on results obtained from recent experimental models, a disturbed distribution of gap junction proteins and cardiac sodium channels may also be observed in AC phenotypes, secondary to desmosomal dysfunction. The study from Noorman et al. examined heart sections from patients diagnosed with AC and performed immunohistochemical analyses of N-cadherin, PKP2, PKG, Cx43 and the cardiac sodium channel NaV1.5. Altered expression/distribution of Cx43, PKG and NaV1.5 was found in most cases of patients with AC. The altered expression and/or distribution of NaV1.5 channels in AC hearts may play a mechanistic role in the arrhythmias leading to sudden cardiac death in AC patients. Thus, NaV1.5 should be considered as a supplemental element in the evaluation of risk stratification and management strategies. However, additional experiments are required to clearly understand the mechanisms leading to AC phenotypes.

Bullous pemphigoid: therapeutic algrorithm and practical management

Introduction: Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucosae. BP typically affects the elderly and manifests with severe itch, localised or generalised eczematous, urticated and/or bullous lesions. Its morbidity and impact on the quality of life are important. The disease is significantly associated with neurological disorders, such as stroke, Parkinson disease, major cognitive impairment and multiple sclerosis. Diagnosis of BP critically relies on immunopathologic examinations, particularly direct immunofluorescence microscopy studies. Areas covered: This paper looks at the evidence of therapies commonly used in bullous pemphigoid. Expert opinion: Treatment of BP has been a challenge, given the relative rarity of the disease, lack of good quality randomised controlled trials, the presence of co-morbidities in the affected elderly population and the high mortality rate. Recent controlled studies have indicated that potent topical corticosteroids constitute a more effective therapy for BP when compared to oral corticosteroids in terms of control of the disease, side effect profile and overall survival. Other therapies have been employed with varying success, but are not validated yet. Improved knowledge of the pathophysiology of BP will hopefully allow the development of new immunomodulatory treatments for this debilitating disease.

Molecular epidemiology of vancomycin-resistant Enterococcus faecium: a prospective, multicenter study in South American hospitals.

Enterococcus faecium has emerged as an important nosocomial pathogen worldwide, and this trend has been associated with the dissemination of a genetic lineage designated clonal cluster 17 (CC17). Enterococcal isolates were collected prospectively (2006 to 2008) from 32 hospitals in Colombia, Ecuador, Perú, and Venezuela and subjected to antimicrobial susceptibility testing. Genotyping was performed with all vancomycin-resistant E. faecium (VREfm) isolates by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing. All VREfm isolates were evaluated for the presence of 16 putative virulence genes (14 fms genes, the esp gene of E. faecium [espEfm], and the hyl gene of E. faecium [hylEfm]) and plasmids carrying the fms20-fms21 (pilA), hylEfm, and vanA genes. Of 723 enterococcal isolates recovered, E. faecalis was the most common (78%). Vancomycin resistance was detected in 6% of the isolates (74% of which were E. faecium). Eleven distinct PFGE types were found among the VREfm isolates, with most belonging to sequence types 412 and 18. The ebpAEfm-ebpBEfm-ebpCEfm (pilB) and fms11-fms19-fms16 clusters were detected in all VREfm isolates from the region, whereas espEfm and hylEfm were detected in 69% and 23% of the isolates, respectively. The fms20-fms21 (pilA) cluster, which encodes a putative pilus-like protein, was found on plasmids from almost all VREfm isolates and was sometimes found to coexist with hylEfm and the vanA gene cluster. The population genetics of VREfm in South America appear to resemble those of such strains in the United States in the early years of the CC17 epidemic. The overwhelming presence of plasmids encoding putative virulence factors and vanA genes suggests that E. faecium from the CC17 genogroup may disseminate in the region in the coming years.

Das Geschlecht der Diplomatie. Geschlechterrollen in den Außenbeziehungen vom Spätmittelalter bis zum 20. Jahrhundert

Fürstinnen in Friedensverhandlungen, Botschaftergattinnen, die ihre Ehemänner in diplomatischen Verhandlungen unterstützen, eine Frau als erste offiziell akkreditierte Botschafterin der Sowjetunion, die Außenpolitik des wilhelminischen Deutschland unter dem Verdacht der Homosexualität: Der vorliegende Sammelband widmet sich der Frage, welche Rolle das Geschlecht und die mit ihm assoziierten Eigenschaften in der diplomatischen Praxis spielten. Unter welchen Umständen konnte die Geschlechtszugehörigkeit vor andere Kategorien wie Stand, Alter, Erfahrung oder Bildung treten, in welchen Kontexten wurde sie zur Nebensache? Ausgehend von Einzelfallstudien steckt der epochenübergreifend angelegte Sammelband ein neues Forschungsfeld ab und legt somit einen Grundstein für eine Geschlechtergeschichte von Außenpolitik.

Jospeh. Furttenbach. Lebenslauff (1652 – 1664)

Joseph Furttenbach (1591 1667) wirkte als Architekt, Ingenieur, Baumeister, Sammler, Chronist und Tagebuchschreiber in der ersten Hälfte des 17. Jahrhunderts. Seine autobiographischen Aufzeichnungen sind bisher unveröffentlicht geblieben. Sie werfen faszinierende Schlaglichter auf das Leben eines protestantischen Vermittlers italienischer Barockkultur im Süden des Alten Reiches, auf die kulturellen und sozialen Aktivi täten eines Kunstkammerbesitzers sowie den Alltag eines Stadtbaumeisters und frommen Lutheraners in der Reichsstadt Ulm.