Epitranscriptomic events such as adenosine‐to‐inosine (A‐to‐I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q‐to‐R transition in the interactive C‐terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient‐derived RNA‐Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases. Using mice with only impaired FLNA editing, we observed increased vascular contraction and diastolic hypertension accompanied by increased myosin light chain phosphorylation, arterial remodeling, and left ventricular wall thickening, which eventually causes cardiac remodeling and reduced systolic output. These results demonstrate a causal relationship between RNA editing and the development of cardiovascular disease indicating that a single epitranscriptomic RNA modification can maintain cardiovascular health.

BackgroundVesicovaginal fistulas (VVF) are the most commonly acquired fistulas of the urinary tract, but we lack a standardized algorithm for their management. Surgery is the most commonly preferred approach to treat women with primary VVF following benign gynaecologic surgery.ObjectiveTo carry out a systematic review and meta-analysis on the effectiveness of operative techniques or conservative treatment for patients with postsurgical VVF. Our secondary objective was to define the surgical time and determine the types of study designs.MethodsPubMed, Old Medline, Embase and Cochrane Central Register of Controlled Trials were used as data sources. This systematic review was modelled on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, including a registration number (CRD42012002097).ResultsWe reviewed 282 full text articles to identify 124 studies for inclusion. In all, 1379/1430 (96.4%) patients were treated surgically. Overall, the transvaginal approach was performed in the majority of patients (39%), followed by a transabdominal/transvesical route (36%), a laparoscopic/robotic approach (15%) and a combined transabdominal-transvaginal approach in 3% of cases. Success rate of conservative treatment was 92.86% (95%CI: 79.54–99.89), 97.98% in surgical cases (95% CI: 96.13–99.29) and 91.63% (95% CI: 87.68–97.03) in patients with prolonged catheter drainage followed by surgery. 79/124 studies (63.7%) provided information for the length of follow-up, but showed a poor reporting standard regarding prognosis. Complications were studied only selectively. Due to the inconsistency of these data it was impossible to analyse them collectively.ConclusionsAlthough the literature is imprecise and inconsistent, existing studies indicate that operation, mainly through a transvaginal approach, is the most commonly preferred treatment strategy in females with postsurgical VVF. Our data showed no clear odds-on favorite regarding disease management as well as surgical approach and current evidence on the surgical management of VVF does not allow any accurate estimation of success and complication rates. Standardisation of the terminology is required so that VVF can be managed with a proper surgical treatment algorithm based on characteristics of the fistula.

ObjectivesTo examine whether a mixed lipid emulsion reduces the incidence of parenteral nutrition associated cholestasis (PNAC) in extremely low birth weight (ELBW, <1000 g) infants.Study designThis double-blind randomized trial of 230 ELBW infants (June 2012-October 2015) was performed at a single level IV neonatal intensive care unit. Patients received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil-(intervention) or a soybean oil-based lipid emulsion (control) for parenteral nutrition. The primary outcome measure was PNAC (conjugated bilirubin >1.5 mg/dL [25 μmol/L] at 2 consecutive measurements). The study was powered to detect a reduction of PNAC from 25% to 10%.ResultsReasons for noneligibility of 274 infants screened were refusal to participate (n = 16), death (n = 10), withdrawal of treatment (n = 5), higher order multiples (n = 9), and parents not available for consent (n = 4). Intention to treat analysis was carried out in 223 infants (7 infants excluded after randomization). Parenteral nutrition associated cholestasis was 11 of 110 (10.1%) in the intervention and 18 of 113 (15.9%) in the control group (P = .20). Multivariable analyses showed no statistically significant difference in the intention to treat (aOR 0.428, 95% CI 0.155-1.187; P = .10) or per protocol population (aOR 0.457, 95% CI 0.155-1.347; P = .16). There was no statistically significant effect on any other neonatal morbidity.ConclusionsThe incidence of parenteral nutrition associated cholestasis was not significantly reduced using a mixed lipid emulsion in ELBW infants.Trial RegistrationClinicalTrials.gov NCT01585935.

Background: Immunoadsorption (IAS) and therapeutic plasma exchange (TPE) are considered safe although fibrinogen is removed. To date no comparison of fibrinogen reduction and associated risk of bleeding in apheresis exists. Methods: Retrospective analysis of TPE, three IAS adsorbers, and combined TPE/IAS regarding fibrinogen reduction and bleeding incidence in 67 patients (1,032 treatments). Results: TPE and TPE/IAS reduced fibrinogen by 64 ± 11% and 58 ± 9%, leading to concentrations <100 mg/dl in 20 and 17% of treatments, respectively. IAS decreased fibrinogen less than TPE (26 ± 6%, p < 0.0001), resulting in fibrinogen concentrations <100 mg/dl in 1% of treatments. The processed volume correlated with reduction in TPE (r = 0.64, p < 0.01), but not in IAS. Bleeding occurred in 1.3% (IAS), 2.3% (TPE) and 3.1% (TPE/IAS) of treatments. Conclusion: Hypofibrinogenemia occurs in 20% of patients after TPE and TPE/IAS, but rarely after IAS. IAS removes fibrinogen independently of volume processed. Overall, bleeding is rare in apheresis.

MRP-8/14 in saliva might be a potential diagnostic parameter for periodontal disease.