LINC01013 Is a Determinant of Fibroblast Activation and Encodes a Novel Fibroblast-Activating Micropeptide.

Myocardial fibrosis confers an almost threefold mortality risk in heart disease. There are no prognostic therapies and novel therapeutic targets are needed. Many thousands of unannotated small open reading frames (smORFs) have been identified across the genome with potential to produce micropeptides (< 100 amino acids). We sought to investigate the role of smORFs in myocardial fibroblast activation.Analysis of human cardiac atrial fibroblasts (HCFs) stimulated with profibrotic TGFß1 using RNA sequencing (RNA-Seq) and ribosome profiling (Ribo-Seq) identified long intergenic non-coding RNA LINC01013 as TGFß1 responsive and containing an actively translated smORF. Knockdown of LINC01013 using siRNA reduced expression of profibrotic markers at baseline and blunted their response to TGFß1. In contrast, overexpression of a codon-optimised smORF invoked a profibrotic response comparable to that seen with TGFß1 treatment, whilst FLAG-tagged peptide associated with the mitochondria.Together, these data support a novel LINC01013 smORF micropeptide-mediated mechanism of fibroblast activation. TGFß1 stimulation of atrial fibroblasts induces expression of LINC01013, whose knockdown reduces fibroblast activation. Overexpression of a smORF contained within LINC01013 localises to mitochondria and activates fibroblasts.

Emergency room closed reduction versus in situ splinting in the treatment of paediatric supracondylar humerus fractures.

PURPOSE: Displaced supracondylar humerus fractures are treated with open or closed reduction and percutaneous pinning. In 2012, our management of patients with a displaced fracture changed from closed reduction in the emergency department (ED) to in situ splinting prior to closed reduction and pinning in the operating room (OR). The purpose of this study was to investigate if outcomes or complications differ between these two management methods. METHODS: Patients less than ten years old with a Gartland type II or III supracondylar humerus fracture between 2008 and 2016 were included. Cases of polytrauma were excluded. Radiographic outcomes were assessed at follow-up. The Fisher's exact test was used for categorical variables and the Wilcoxon rank sums tests for continuous variables. RESULTS: In all, 157 patients were included, 89 with reduction in the ED and 68 without. There was no significant difference between the groups related to demographic factors or fracture characteristics. Patients managed without reduction in the ED had a lower average delay from ED to OR compared with those treated with reduction (16 hours versus 22 hours, p < 0.005) and a shorter hospital length of stay (34 hours versus 40 hours, p < 0.005). CONCLUSION: No difference in complications or outcomes was found between patients with Type II or III supracondylar fractures treated initially with or without closed reduction in the ED. Patients treated without ED reduction were taken to the OR sooner and remained in the hospital for a shorter period of time. Splinting in situ reduces anaesthesia exposure without increasing postoperative complications or suboptimal outcomes. LEVEL OF EVIDENCE: Level III, retrospective comparative study.