Durability of Tricuspid Valve Repair in Patients Undergoing Left Ventricular Assist Device Implantation.

Objectives: Benefits of tricuspid valve repair (TVR) in left ventricular assist device (LVAD) patients have been questioned. High TVR failure rates have been reported. Remaining or recurring TR was found to be a risk factor for right heart failure (RHF). Therefore, we assessed our experience. Methods: Since 12/2010, 195 patients have undergone LVAD implantation in our center. Almost half (n = 94, 48%) received concomitant TVR (LVAD+TVR). These patients were included in our analysis. Echocardiographic and clinical data were assessed. Median follow-up was 2.8 years (7 days-0.6 years). Results were correlated with clinical outcomes. Results: LVAD+TVR patients were 59.8 ± 11.4 years old (89.4% male) and 37.3% were INTERMACS level 1 and 2. Preoperative TR was moderate in 28 and severe in 66 patients. RV function was severely impaired in 61 patients reflected by TAPSE-values of 11.2 ± 2.9 mm (vs. 15.7 ± 3.8 mm in n = 33; p < 0.001). Risk for RHF according to EUROMACS-RHF risk score was high (>4 points) in 60 patients, intermediate (>2-4 points) in 19 and low (0-2 points) in 15. RHF occurred in four patients (4.3%). Mean duration of echocardiographic follow-up was 2.8 ± 2.3 years. None of the patients presented with severe and only five (5.3%) with moderate TR. The vast majority (n = 63) had mild TR, and 26 patients had no/trace TR. Survival at 1, 3 and 5 years was 77.4%, 68.1% and 55.6%, 30-day mortality was 11.7% (n = 11). Heart transplantation was performed in 12 patients (12.8%). Conclusions: Contrary to expectations, concomitant TVR during LVAD implantation may result in excellent repair durability, which appears to be associated with low risk for RHF.

Twist regulates Yorkie activity to guide lineage reprogramming of syncytial alary muscles.

Genesis of syncytial muscles is typically considered as a paradigm for an irreversible developmental process. Notably, transdifferentiation of syncytial muscles is naturally occurring during Drosophila development. The ventral longitudinal heart-associated musculature (VLM) arises by a unique mechanism that revokes differentiation states of so-called alary muscles and comprises at least two distinct steps: syncytial muscle cell fragmentation into single myoblasts and successive reprogramming into founder cells that orchestrate de novo fiber formation of the VLM lineage. Here, we provide evidence that the mesodermal master regulator twist plays a key role during this reprogramming process. Acting downstream of Drosophila Tbx1 (Org-1), Twist is regulating the activity of the Hippo pathway effector Yorkie and is required for the initiation of syncytial muscle dedifferentiation and fragmentation. Subsequently, fibroblast growth factor receptor (FGFR)-Ras-mitogen-activated protein kinase (MAPK) signaling in resulting mononucleated myoblasts maintains Twist expression, thereby stabilizing nuclear Yorkie activity and inducing their lineage switch into founder cells of the VLM.

Yorkie and JNK revert syncytial muscles into myoblasts during Org-1-dependent lineage reprogramming.

Lineage reprogramming has received increased research attention since it was demonstrated that lineage-restricted transcription factors can be used in vitro for direct reprogramming. Recently, we reported that the ventral longitudinal musculature of the adult Drosophila heart arises in vivo by direct lineage reprogramming from larval alary muscles, a process that starts with the dedifferentiation and fragmentation of syncytial muscle cells into mononucleate myoblasts and depends on Org-1 (Drosophila Tbx1). Here, we shed light on the events occurring downstream of Org-1 in this first step of transdifferentiation and show that alary muscle lineage-specific activation of Yorkie plays a key role in initiating the dedifferentiation and fragmentation of these muscles. An additional necessary input comes from active dJNK signaling, which contributes to the activation of Yorkie and furthermore activates dJun. The synergistic activities of the Yorkie/Scalloped and dJun/dFos transcriptional activators subsequently initiate alary muscle fragmentation as well as up-regulation of Myc and piwi, both crucial for lineage reprogramming.

Chironomus riparius (Diptera) genome sequencing reveals the impact of minisatellite transposable elements on population divergence.

Active transposable elements (TEs) may result in divergent genomic insertion and abundance patterns among conspecific populations. Upon secondary contact, such divergent genetic backgrounds can theoretically give rise to classical Dobzhansky-Muller incompatibilities (DMI), thus contributing to the evolution of endogenous genetic barriers and eventually causing population divergence. We investigated differential TE abundance among conspecific populations of the nonbiting midge Chironomus riparius and evaluated their potential role in causing endogenous genetic incompatibilities between these populations. We focussed on a Chironomus-specific TE, the minisatellite-like Cla-element, whose activity is associated with speciation in the genus. Using a newly generated and annotated draft genome for a genomic study with five natural C. riparius populations, we found highly population-specific TE insertion patterns with many private insertions. A significant correlation of the pairwise FST estimated from genomewide single-nucleotide polymorphisms (SNPs) and the FST estimated from TEs is consistent with drift as the major force driving TE population differentiation. However, the significantly higher Cla-element FST level due to a high proportion of differentially fixed Cla-element insertions also indicates selection against segregating (i.e. heterozygous) insertions. With reciprocal crossing experiments and fluorescent in situ hybridization of Cla-elements to polytene chromosomes, we documented phenotypic effects on female fertility and chromosomal mispairings. We propose that the inferred negative selection on heterozygous Cla-element insertions may cause endogenous genetic barriers and therefore acts as DMI among C. riparius populations. The intrinsic genomic turnover exerted by TEs may thus have a direct impact on population divergence that is operationally different from drift and local adaptation.

Self-reported hand eczema in a hospital population.

Occupational skin diseases are frequent in the healthcare sector. The objective of this study was to obtain baseline data on hand eczema and risk factors for hand eczema in an unselected hospital population. A questionnaire study on hand eczema and risk factors for hand eczema was performed among hospital employees at a middle-size Danish hospital. A total of 1909 employees from all job groups and all departments were included. Response rate was 65.3%. The overall frequency of self-reported hand eczema within the past 12 months was 23%. Divided into job groups, the frequencies varied from 8% to 32% and were significantly higher among assistant nurses (32%), nurses (30%), and nursing aids (27%). For the individual departments, the hand eczema frequencies varied from 7% to 50%, with the highest frequencies reported at medical and surgical wards. Occupational risk factors for hand eczema such as use of protective gloves and hand washing were significantly more frequent among respondents with hand eczema within the past year, which suggests a potential for prevention through workplace interventions. In conclusion, high frequencies of hand eczema were observed among assistant nurses, nurses, and nursing aids. Hand eczema was more frequent among women and in the younger age groups.