Charité

About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.

Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement

Abstract: Rapid innovations in cardiovascular magnetic resonance (CMR) now permit the routine acquisition of quantitative measures of myocardial and blood T1 which are key tissue characteristics. These capabilities introduce a new frontier in cardiology, enabling the practitioner/investigator to quantify biologically important myocardial properties that otherwise can be difficult to ascertain clinically. CMR may be able to track biologically important changes in the myocardium by: a) native T1 that reflects myocardial disease involving the myocyte and interstitium without use of gadolinium based contrast agents (GBCA), or b) the extracellular volume fraction (ECV)–a direct GBCA-based measurement of the size of the extracellular space, reflecting interstitial disease. The latter technique attempts to dichotomize the myocardium into its cellular and interstitial components with estimates expressed as volume fractions. This document provides recommendations for clinical and research T1 and ECV measurement, based on published evidence when available and expert consensus when not. We address site preparation, scan type, scan planning and acquisition, quality control, visualisation and analysis, technical development. We also address controversies in the field. While ECV and native T1 mapping appear destined to affect clinical decision making, they lack multi-centre application and face significant challenges, which demand a community-wide approach among stakeholders. At present, ECV and native T1 mapping appear sufficiently robust for many diseases; yet more research is required before a large-scale application for clinical decision-making can be recommended.

The global burden of injury: incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013

Abstract: Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.

Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function

Abstract: INTRODUCTION Recently, a special class of RNAs has excited researchers and triggered hundreds of now-published studies. Known as circular RNAs (circRNAs), these RNAs are produced by regular transcription from genomic DNA, but the two ends of the (usually) exonic transcripts are covalently closed, probably in most cases by noncanonical splice reactions. Most circRNAs are expressed in the cytoplasm and are unusually stable, suggesting that they may have functions that diverge from those of canonical messenger RNAs (mRNAs) or long noncoding RNAs (lncRNAs). CircRNAs tend to be weakly expressed, but there are exceptions in animal brains. For example, in the mouse brain, a few hundred circRNAs are highly expressed, often with developmentally specific expression patterns that are conserved in the human brain. We previously proposed that circRNAs may, at least sometimes, serve as regulatory RNAs. A circRNA discovered by the Kjems laboratory, CDR1as, caught our attention because it was covered with >70 binding sites for the microRNA (miRNA) miR-7. Our data suggested that CDR1as might serve to alter the free concentration of miR-7. But what really is the function of CDR1as? RATIONALE We first determined which miRNAs specifically bind Cdr1as in postmortem human and mouse brains and characterized Cdr1as expression patterns. Once we had that information, we removed Cdr1as from the mouse genome to study the molecular and behavioral consequences. RESULTS We show that Cdr1as is, in the human brain, directly and massively bound by miR-7 and miR-671. In fact, Cdr1as is one of the most common transcripts targeted by miRNAs out of all brain mRNAs or lncRNAs. The expression of miRNAs was generally unperturbed in Cdr1as knockout (KO) mice, with the exception of the two miRNAs that directly interact with Cdr1as, miR-7 and miR-671, which were respectively down-regulated and up-regulated. This perturbation was posttranscriptional, consistent with a model in which Cdr1as interacts with these miRNAs in the cytoplasm. We show that Cdr1as is highly expressed (hundreds of copies within neurons) in somas and neurites, but not in glial cells. The expression of many immediate early genes (IEGs), which are markers of neuronal activity, was consistently up-regulated in KO animals. For example, c-Fos and a few other miR-7 targets were up-regulated, suggesting that IEG up-regulation can in part be explained by miR-7 down-regulation and that Cdr1as modulates neuronal activity. Cdr1as KO mice showed a strong deficit in prepulse inhibition of the startle response, a sensorimotor gating phenotype that is impaired in several human neuropsychiatric disorders. Electrophysiological measurements indicated an increase in spontaneous vesicle release in Cdr1as KO neurons, suggesting that Cdr1as plays a role in regulating synaptic transmission. CONCLUSION Mechanistically, our data indicate that Cdr1as regulates miR-7 stability or transport in neurons, whereas miR-671 regulates Cdr1as levels. Functionally, our data suggest that Cdr1as and its direct interactions with miRNAs are important for sensorimotor gating and synaptic transmission. More generally, because the brain is an organ with exceptionally high and diverse expression of circRNAs, our data suggest the existence of a previously unknown layer of biological functions carried out by circRNAs.