Corticosteroids in patients with vestibular neuritis: An updated meta‐analysis

Vestibular neuritis is a common neuro-otological entity. Therapeutically, corticosteroids are advised, although the evidence is limited. The objective of this review is to update meta-analyses of clinical trials that address the question of whether patients with vestibular neuritis treated with corticosteroids show better recovery than control patients. The electronic databases Medline, Scopus and Cochrane were searched for clinical trials for the years 1970-2020 without language restriction. Data were extracted, and outcome parameters were subjected to conventional and cumulative meta-analysis using a commercially available software program (www.meta-analysis.com). Finally, 15 trials with 363 participants in the treatment and 489 in the control groups were identified and could be included. Eight studies were judged to be at high risk of bias. The odds ratio (OR) for good outcome in the acute phase was 3.1 (95% CI 1.2-7.8; p = .015) in favour of steroid treatment leading to the number needed to treat (NNT) = 6 (95% CI 4-23). The odds ratio (OR) for restoration of vestibular function in the follow-up was 2.4 (95% CI 1.3-4.4; p = .004) for the benefit of steroid treatment resulting in a NNT = 7 (95% CI 5-18). The results of the cumulative statistics did not differ. The risk of adverse effects was higher in patients treated with steroids with an OR of 10.9 (95% CI 1.3-93.8; p = .015) and an estimated number needed to harm (NNH) = 4 (95% CI 3-19). The advantage for corticosteroids remained when differentiating between patients who participated in randomized or non-randomized clinical trials. Steroid treatment in vestibular neuritis resulted in a statistically significant benefit compared to control therapies. However, broad heterogeneity of the studies, mostly low-grade quality of studies, high risk of bias and broad confidence intervals put the findings into perspective allowing only a careful judgement of some benefit of corticosteroids. The findings, however, support the call for an adequately powered and well-designed randomized controlled trial to re-evaluate the effectiveness of corticosteroids

BLISTER Regulates Polycomb-Target Genes, Represses Stress-Regulated Genes and Promotes Stress Responses in Arabidopsis thaliana

Polycomb group (PcG) proteins are key epigenetic regulators of development. The highly conserved Polycomb repressive complex 2 (PRC2) represses thousands of target genes by trimethylating H3K27 (H3K27me3). Plant specific PcG components and functions are largely unknown, however, we previously identified the plant-specific protein BLISTER (BLI) as a PRC2 interactor. BLI regulates PcG target genes and promotes cold stress resistance. To further understand the function of BLI, we analyzed the transcriptional profile of bli-1 mutants. Approximately 40% of the up-regulated genes in bli are PcG target genes, however, bli-1 mutants did not show changes in H3K27me3 levels at all tested genes, indicating that BLI regulates PcG target genes downstream of or in parallel to PRC2. Interestingly, a significant number of BLI regulated H3K27me3 target genes is regulated by the stress hormone absciscic acid (ABA). We further reveal an overrepresentation of genes responding to abiotic stresses such as drought, high salinity, or heat stress among the up- regulated genes in bli mutants. Consistently, bli mutants showed reduced desiccation stress tolerance. We conclude that the PRC2 associated protein BLI is a key regulator of stress-responsive genes in Arabidopsis: it represses ABA-responsive PcG target genes, likely downstream of PRC2, and promotes resistance to several stresses such as cold and drought

Cardiac transcriptional and metabolic changes following thoracotomy

Non-cardiac surgery is associated with significant cardiovascular complications. Reported mortality rate ranges from 1.9% to 4% in unselected patients. A postoperative surge in pro-inflammatory cytokines is a well-known feature and putative contributor to these complications. Despite much clinical research, little is known about the biomolecular changes in cardiac tissue following non-cardiac surgery. In order to increase our understanding, we analyzed whole-transcriptional and metabolic profiling data sets from hearts of mice harvested two, four, and six weeks following isolated thoracotomy. Hearts from healthy litter-mates served as controls. Functional network enrichment analyses showed a distinct impact on cardiac transcription two weeks after surgery characterized by a downregulation of mitochondrial pathways in the absence of significant metabolic alterations. Transcriptional changes were not detectable four and six weeks following surgery. Our study shows distinct and reversible transcriptional changes within the first two weeks following isolated thoracotomy. This coincides with a time period, in which most cardiovascular events happen

Deutscher Freiwilligensurvey: Kurzbeschreibung des Scientific Use File FWS Trend 1999-2014, Version 1.0

In der vorliegenden Kurzbeschreibung wird der Trenddatensatz des Deutschen Freiwilligensurveys (FWS) 1999-2014 dargestellt. Der Scientific Use File (SUF) FWS Trend 1999-2014 umfasst Informationen aus den vier Erhebungswellen von 1999 bis 2014 des FWS und kann für wellenübergreifende Analysen des FWS verwendet werden. Der FWS ist eine seit 1999 im fünfjährlichen Abstand durchgeführte repräsentative Befragung zum freiwilligen Engagement in Deutschland, die sich an Personen ab 14 Jahren richtet. In telefonischen Interviews werden umfassende Angaben zum Inhalt, zum Umfang, zu Motiven und zum Kontext des freiwilligen Engagements erhoben sowie die Spendentätigkeit und die Engagementbereitschaft erfragt. Die Daten ermöglichen es nach Bevölkerungsgruppen und Landesteilen zu differenzieren. Der FWS ist damit die wesentliche Grundlage der Sozialberichterstattung zum freiwilligen Engagement in Deutschland. Er wird aus Mitteln des Bundesministeriums für Familie, Senioren, Frauen und Jugend (BMFSFJ) gefördert. Bis einschließlich 2009 wurden die Erhebungen von Kantar Public (ehemals TNS Infratest Sozialforschung bzw. Infratest Burke) geleitet und durchgeführt. Seit Ende 2011 liegt die wissenschaftliche Leitung beim Deutschen Zentrum für Altersfragen (DZA). Die Datenerhebung der vierten Welle wurde von infas Institut für angewandte Sozialwissenschaft im Jahr 2014 durchgeführt. Die Datensätze aller vier Erhebungswellen wurden vom DZA als SUF aufbereitet und werden auf Antrag vom Forschungsdatenzentrum (FDZ-DZA) für wissenschaftliche Nutzungszwecke kostenfrei zur Verfügung gestellt

Sepsis related mortality of extremely low gestational age newborns after the introduction of colonization screening for multi-drug resistant organisms

Background: In 2013 German infection surveillance guidelines recommended weekly colonization screening for multidrug-resistant (MDRO) or highly epidemic organisms for neonatal intensive care units (NICUs) and extended hygiene measures based on screening results. It remains a matter of debate whether screening is worth the effort. We therefore aimed to evaluate sepsis related outcomes before and after the guideline update. Methods: The German Neonatal Network (GNN) is a prospective cohort study including data from extremely preterm infants between 22 + 0 and 28 + 6 gestational weeks born in 62 German level III NICUs. Results: Infants treated after guideline update (n = 8.903) had a lower mortality (12.5% vs. 13.8%, p = 0.036), reduced rates for clinical sepsis (31.4 vs. 42.8%, p < 0.001) and culture-proven sepsis (14.4% vs. 16.5%, p = 0.003) as compared to infants treated before update (n = 3.920). In a multivariate logistic regression analysis, nine pathogens of cultureproven sepsis were associated with sepsis-related death, e.g. Pseudomonas aeruginosa [OR 59 (19–180), p < 0.001)]. However, the guideline update had no significant effect on pathogen-specific case fatality, total sepsis-related mortality and culture-proven sepsis rates with MDRO. While the exposure of GNN infants to cefotaxime declined over time (31.1 vs. 40.1%, p < 0.001), the treatment rate with meropenem was increased (31.6 vs. 26.3%, p < 0.001). Conclusions: The introduction of weekly screening and extended hygiene measures is associated with reduced sepsis rates, but has no effects on sepsis-related mortality and sepsis with screening-relevant pathogens. The high exposure rate to meropenem should be a target of antibiotic stewardship programs

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe