A Deletion in the VLDLR Gene in Eurasier Dogs with Cerebellar Hypoplasia Resembling a Dandy-Walker-Like Malformation (DWLM).

Dandy-Walker-like malformation (DWLM) is the result of aberrant brain development and mainly characterized by cerebellar hypoplasia. DWLM affected dogs display a non-progressive cerebellar ataxia. Several DWLM cases were recently observed in the Eurasier dog breed, which strongly suggested a monogenic autosomal recessive inheritance in this breed. We performed a genome-wide association study (GWAS) with 9 cases and 11 controls and found the best association of DWLM with markers on chromosome 1. Subsequent homozygosity mapping confirmed that all 9 cases were homozygous for a shared haplotype in this region, which delineated a critical interval of 3.35 Mb. We sequenced the genome of an affected Eurasier and compared it with the Boxer reference genome and 47 control genomes of dogs from other breeds. This analysis revealed 4 private non-synonymous variants in the critical interval of the affected Eurasier. We genotyped these variants in additional dogs and found perfect association for only one of these variants, a single base deletion in the VLDLR gene encoding the very low density lipoprotein receptor. This variant, VLDLR:c.1713delC is predicted to cause a frameshift and premature stop codon (p.W572Gfs*10). Variants in the VLDLR gene have been shown to cause congenital cerebellar ataxia and mental retardation in human patients and Vldlr knockout mice also display an ataxia phenotype. Our combined genetic data together with the functional knowledge on the VLDLR gene from other species thus strongly suggest that VLDLR:c.1713delC is indeed causing DWLM in Eurasier dogs.

Herzunterstützungspumpe (VAD) bei Herzinsuffizienz - Langzeitbetreuung von Patienten mit VAD

In der Schweiz leben aktuell ca. 200 000 Menschen mit einer Herzinsuffizienz. Weltweit sind es zirka 23 Millionen Betroffene (1, 2). Die Prävalenz für eine Herzinsuffizienz steigt durch die höhere Lebenserwartung und die Fortschritte der Medizin. Nach wie vor ist die optimale medikamentöse Therapie (Tab. 1) der erste und wichtigste Eckpfeiler in der Behandlung, um das schwache Herz optimal zu entlasten und zu unterstützen. Die Vermittlung und Schulung der notwendigen Anpassung des Lebensstils durch ausgebildetes Personal im Rahmen einer Herzinsuffizienzberatung gehört ebenso zur Behandlung. So gelingt es, viele Patienten über eine gewisse Zeit zu stabilisieren oder sogar die Herzinsuffizienz zu verbessern. Nichtsdestotrotz handelt es sich in den meisten Fällen um eine fortschreitende Erkrankung.

Protocol for a randomized, placebo-controlled, double-blind clinical trial investigating sacral neuromodulation for neurogenic lower urinary tract dysfunction

BACKGROUND Sacral neuromodulation has become a well-established and widely accepted treatment for refractory non-neurogenic lower urinary tract dysfunction, but its value in patients with a neurological cause is unclear. Although there is evidence indicating that sacral neuromodulation may be effective and safe for treating neurogenic lower urinary tract dysfunction, the number of investigated patients is low and there is a lack of randomized controlled trials. METHODS AND DESIGN This study is a prospective, randomized, placebo-controlled, double-blind multicenter trial including 4 sacral neuromodulation referral centers in Switzerland. Patients with refractory neurogenic lower urinary tract dysfunction are enrolled. After minimally invasive bilateral tined lead placement into the sacral foramina S3 and/or S4, patients undergo prolonged sacral neuromodulation testing for 3-6 weeks. In case of successful (defined as improvement of at least 50% in key bladder diary variables (i.e. number of voids and/or number of leakages, post void residual) compared to baseline values) prolonged sacral neuromodulation testing, the neuromodulator is implanted in the upper buttock. After a 2 months post-implantation phase when the neuromodulator is turned ON to optimize the effectiveness of neuromodulation using sub-sensory threshold stimulation, the patients are randomized in a 1:1 allocation in sacral neuromodulation ON or OFF. At the end of the 2 months double-blind sacral neuromodulation phase, the patients have a neuro-urological re-evaluation, unblinding takes place, and the neuromodulator is turned ON in all patients. The primary outcome measure is success of sacral neuromodulation, secondary outcome measures are adverse events, urodynamic parameters, questionnaires, and costs of sacral neuromodulation. DISCUSSION It is of utmost importance to know whether the minimally invasive and completely reversible sacral neuromodulation would be a valuable treatment option for patients with refractory neurogenic lower urinary tract dysfunction. If this type of treatment is effective in the neurological population, it would revolutionize the management of neurogenic lower urinary tract dysfunction. TRIAL REGISTRATION TRIAL REGISTRATION NUMBER http://www.clinicaltrials.gov; Identifier: NCT02165774.

Sex as a source of power? Backlash against self-sexualizing women

Although women are thought to possess sexual power, they risk social and economic penalties (i.e., backlash; Rudman, 1998) when they self-sexualize (i.e., assert their power; Cahoon & Edmonds, 1989; Glick, Larsen, Johnson, & Branstiter, 2005). Why? Drawing on the status incongruity hypothesis (SIH), which predicts backlash against powerful women because they challenge the gender hierarchy, we expected prejudice against self-sexualizing women to be explained by a dominance penalty rather than a communality deficit (Rudman, Moss-Racusin, Phelan, & Nauts, 2012). Two experiments supported this hypothesis, and Experiment 3 further showed that the dominance penalty was explained by ascribing power motives to self-sexualized women. These findings extend the SIH’s utility to the domain of self-sexualization and illuminate the scope of people’s discomfort with female power. Implications for the advancement of gender equality are discussed.

Communion-over-Agency effects on advertising effectiveness

Gender-stereotypical portrayals of communal women and agentic men are highly common in advertising. But past research indicates that advertising effectiveness is higher when endorsers are portrayed as communal – irrespective of their gender. The aim of the current research is to explore this communion-over-agency effect on advertising effectiveness and its underlying mechanism. Two studies provide evidence for a communion-over-agency effect on advertising effectiveness (i.e., attitude toward the ad and brand). These studies show that the communion-over-agency effect on attitude toward the ad is mediated by endorser likeability (simple mediation). The effect on attitude toward the brand is mediated by endorser likeability and attitude toward the ad (serial multiple mediation). In concert, this research underscores the significance of communion (and agency) on endorser evaluation and advertising effectiveness.

Assessing the sustainability of water governance systems: the sustainability wheel

We present and test a conceptual and methodological approach for interdisciplinary sustainability assessments of water governance systems based on what we call the sustainability wheel. The approach combines transparent identification of sustainability principles, their regional contextualization through sub-principles (indicators), and the scoring of these indicators through deliberative dialogue within an interdisciplinary team of researchers, taking into account their various qualitative and quantitative research results. The approach was applied to a sustainability assessment of a complex water governance system in the Swiss Alps. We conclude that the applied approach is advantageous for structuring complex and heterogeneous knowledge, gaining a holistic and comprehensive perspective on water sustainability, and communicating this perspective to stakeholders.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.