Pre-competition cardiac screening in professional handball players - setting up at the EHF European Handball Championship 2010 in Austria

Zusammenfassung: In vielen Sportarten wird ein regelmäßiges, richtliniengetreues kardiales Screening zur Verhinderung des plötzlichen Herztods noch immer nicht gewährleistet. Wir nahmen die Handball Europameisterschaften, welche 2010 in Wien und weiteren Städten in Österreich stattfanden, zum Anlass, die aktuelle Situation bei Toplevel-Handballern zu untersuchen: Ein standardisierter Fragebogen wurde vor dem Turnier an alle qualifizierten Teams und Spieler versandt. Eine Rücklaufrate von 42,7 % kann zum Schluss führen, dass das Problem des plötzlichen Herztods bei den Spielern und Verantwortlichen unterschätzt wird. Die überwiegende Mehrzahl der Spieler (82 %) wurde gemäß der Auswertung der Fragebögen korrekt, entsprechend der aktuellen Screening-Richtlinien untersucht. In gut der Hälfte der Teams wurde das Screening jedoch "inhomogen" durchgeführt. 5 Spieler (4,1 %) wurden zumindest nicht innerhalb der letzten Jahre untersucht, bei 1 Spieler (0,8 %) wurde kein EKG durchgeführt. Während 69 % der Handballer ihr erstes Screening erst nach dem Alter von 18 Jahren durchliefen, wurden 16 Spieler (13,1 %) gar niemals zuvor einer kardialen Vorsorgeuntersuchung unterzogen. Schließlich identifizierten wir aufgrund der Fragebögen 17 Athleten (13,9 %) mit einer hoch suspekten Anamnese, wovon 2 Athleten (1,6 %) niemals zuvor kardiologisch abgeklärt wurde

Pre-competition cardiac screening in professional handball players - setting up at the EHF European Handball Championship 2010 in Austria

In many sports, regular cardiac screening for exercise-associated sudden cardiac death is still not provided. To set up the current situation in top-skilled handball players qualified for the 2010 European Handball Championship in Austria, a standardised questionnaire was sent to every team. The fact that only 42.7% of the players returned the questionnaire may lead to the conclusion that the awareness of the problem is quite low. However, 82% of these players have been screened according to current recommendations. Half of the teams were screened inhomogeneously: 5 players (4.1%) have not been screened within the last years, 1 athlete (0.8%) was screened without an ECG. While 69% of the athletes got their first screening only after the age of 18, 16 players (13.1%) never went through a specific screening ever. We identified 17 athletes (13.9%) with a highly suspicious history, 2 of them (1.6%) never underwent a medical screening at all

Human Immunodeficiency Virus Type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains

BACKGROUND: The Nef protein of Human Immunodeficiency Viruses optimizes viral spread in the infected host by manipulating cellular transport and signal transduction machineries. Nef also boosts the infectivity of HIV particles by an unknown mechanism. Recent studies suggested a correlation between the association of Nef with lipid raft microdomains and its positive effects on virion infectivity. Furthermore, the lipidome analysis of HIV-1 particles revealed a marked enrichment of classical raft lipids and thus identified HIV-1 virions as an example for naturally occurring membrane microdomains. Since Nef modulates the protein composition and function of membrane microdomains we tested here if Nef also has the propensity to alter microdomain lipid composition. RESULTS: Quantitative mass spectrometric lipidome analysis of highly purified HIV-1 particles revealed that the presence of Nef during virus production from T lymphocytes enforced their raft character via a significant reduction of polyunsaturated phosphatidylcholine species and a specific enrichment of sphingomyelin. In contrast, Nef did not significantly affect virion levels of phosphoglycerolipids or cholesterol. The observed alterations in virion lipid composition were insufficient to mediate Nef's effect on particle infectivity and Nef augmented virion infectivity independently of whether virus entry was targeted to or excluded from membrane microdomains. However, altered lipid compositions similar to those observed in virions were also detected in detergent-resistant membrane preparations of virus producing cells. CONCLUSION: Nef alters not only the proteome but also the lipid composition of host cell microdomains. This novel activity represents a previously unrecognized mechanism by which Nef could manipulate HIV-1 target cells to facilitate virus propagation in vivo

Expanding analytical possibilities concerning the detection of stanozolol misuse by means of high resolution/high accuracy mass spectrometric detection of stanozolol glucuronides in human sports drug testing

Anabolic-androgenic steroids (AAS) represent one of the most frequently detected classes of prohibited substances in doping controls. Due to their long-lasting beneficial effects on athletic performance, utmost retrospectivity via urine analysis is desirable and accomplished by targeting long-term metabolites of the respective drugs. In case of stanozolol, a substantial variety of metabolites has enabled the identification of numerous adverse analytical findings in the past, and recent studies concerning complementary phase-I and phase-II metabolites has further expanded the windows of opportunity for detecting the abuse of stanozolol. In this study, the utility of liquid chromatography-high resolution/high accuracy (tandem) mass spectrometry (LC-MS/MS) for the detection of 3'-OH-stanozolol glucuronide in sports drug testing is presented and the identification of two additional and so far unreported metabolites is shown. The structures of the complementary glucuronic acid conjugates were attributed to stanozolol-N-glucuronide and 17-epistanozolol-N-glucuronide. By means of chemical synthesis, stanozolol-N-glucuronide was prepared and used to corroborate the suggested structures. The 3'-OH-stanozolol glucuronide and the newly identified target compounds were implemented into routine sports drug test assays consisting of direct injection LC-MS/MS or solid-phase extraction (SPE) followed by LC-MS/MS. A considerably expanded detection window for stanozolol abuse was demonstrated compared to the use of conventional phase-I metabolites and methodologies based on, for example, low resolution LC-MS/MS or gas chromatography-tandem mass spectrometry (GC-MS/MS). The commercial availability of 3'-OH-stanozolol glucuronide has been of great value for confirmatory purposes, and 17-epistanozolol-N-glucuronide was found to be a favourable long-term metabolite for doping controls as it was observed up to 28days post-administration of the drug. Applying the established methodology over a period of six months to 659 routine sports drug testing samples, a total of 85 adverse analytical findings was uncovered, 72 of which would have remained undetected using earlier employed GC-MS/MS approaches. Copyright (c) 2013 John Wiley & Sons, Ltd

Revised Cambrian stratigraphy in the Franconian Forest (Frankenwald), Germany, reveals typical West Gondwanan succession in the Saxothuringian Belt

New investigations of the Cambrian in the Franconian Forest region lead to a revision of the lithostratigraphic succession into seven units: Rauschbach Unit, Tiefenbach Formation, Tannenknock Formation (with Galgenberg and Wildenstein members), Triebenreuth Formation, Lippertsgrun Formation and Berglesh of Formation, with partly revised stratigraphical ranges and lithological characteristics. The succession indicates a fairly complete succession from Cambrian Series 2 (late early Cambrian) through the end of the Miaolingian, with gaps being a result of incomplete exposure and structural complexity rather than distinct hiatuses. New finds expand the known fossil record and provide additional data for reconstructing biogeographical relationships and depositional environments. These features indicate shallow marine conditions throughout the Cambrian with characteristics typical for West Gondwanan shelf areas. In particular, strong similarities to the Moroccan Atlas regions are indicated. Additional information on volcanic activity from middle Cambrian through Tremadocian times provides clues for crustal extension that affected the depositional setting in this region. Stratigraphy, depositional environments and facies distribution all suggest reinterpretation of earlier geotectonical models used to interpret the history of the Franconian Forest area in the Saxothuringian Belt

Integration of Cardiac Actin Mutants Causing Hypertrophic (p.A295S) and Dilated Cardiomyopathy (p.R312H and p.E361G) into Cellular Structures

The human mutant cardiac α-actins p.A295S or p.R312H and p.E361G, correlated with hypertrophic or dilated cardiomyopathy, respectively, were expressed by the baculovirus/Sf21 insect cell system and purified to homogeneity. The purified cardiac actins maintained their native state but showed differences in Ca2+-sensitivity to stimulate the myosin-subfragment1 ATPase. Here we analyzed the interactions of these c-actins with actin-binding and -modifying proteins implicated in cardiomyocyte differentiation. We demonstrate that Arp2/3 complex and the formin mDia3 stimulated the polymerization rate and extent of the c-actins, albeit to different degrees. In addition, we tested the effect of the MICAL-1 monooxygenase, which modifies the supramolecular actin organization during development and adaptive processes. MICAL-1 oxidized these c-actin variants and induced their de-polymerization, albeit at different rates. Transfection experiments using MDCK cells demonstrated the preferable incorporation of wild type and p.A295S c-actins into their microfilament system but of p.R312H and p.E361G actins into the submembranous actin network. Transduction of neonatal rat cardiomyocytes with adenoviral constructs coding HA-tagged c-actin variants showed their incorporation into microfilaments after one day in culture and thereafter into thin filaments of nascent sarcomeric structures at their plus ends (Z-lines) except the p.E361G mutant, which preferentially incorporated at the minus ends