Closed midshaft clavicle fractures : an evidence-based triage management algorithm.

AIMS: The management of mid-shaft clavicle fractures (MSCFs) has evolved over the last three decades. Controversy exists over which specific fracture patterns to treat and when. This review aims to synthesize the literature in order to formulate an appropriate management algorithm for these injuries in both adolescents and adults. METHODS: This is a systematic review of clinical studies comparing the outcomes of operative and nonoperative treatments for MSCFs in the past 15 years. The literature was searched using, PubMed, Google scholar, OVID Medline, and Embase. All databases were searched with identical search terms: mid-shaft clavicle fractures (± fixation) (± nonoperative). RESULTS: Using the search criteria identified, 247 studies were deemed eligible. Following initial screening, 220 studies were excluded on the basis that they were duplicates and/or irrelevant to the research question being posed. A total of 27 full-text articles remained and were included in the final review. The majority of the meta-analyses draw the same conclusions, which are that operatively treated fractures have lower nonunion and malunion rates but that, in those fractures which unite (either operative or nonoperative), the functional outcomes are the same at six months. CONCLUSION: With regard to the adolescent population, the existing body of evidence is insufficient to support the use of routine operative management. Regarding adult fractures, the key to identifying patients who benefit from operative management lies in the identification of risk factors for nonunion. We present an algorithm that can be used to guide both the patient and the surgeon in a joint decision-making process, in order to optimize patient satisfaction and outcomes.Cite this article: Bone Jt Open 2022;3(11):850-858

Recognition and discrimination of target mRNAs by Sib RNAs, a cis-encoded sRNA family

Five Sib antitoxin RNAs, members of a family of cis-encoded small regulatory RNAs (sRNAs) in Escherichia coli, repress their target mRNAs, which encode Ibs toxins. This target repression occurs only between cognate sRNA–mRNA pairs with an exception of ibsA. We performed co-transformation assays to assess the ability of SibC derivatives to repress ibsC expression, thereby revealing the regions of SibC that are essential for ibsC mRNA recognition. SibC has two target recognition domains, TRD1 and TRD2, which function independently. The target site for TRD1 is located within the ORF of ibsC, whereas the target site for TRD2 is located in the translational initiation region. The TRD1 sequence is sufficient to repress ibsC expression. In contrast, TRD2 requires a specific structure in addition to the recognition sequence. An in vitro structural probing analysis showed that the initial interactions at these two recognition sites allowed base-pairing to progress into the flanking sequences. Displacement of the TRD1 and TRD2 domains of SibC by the corresponding domains of SibD changed the target specificity of SibC from ibsC to ibsD, suggesting that these two elements modulate the cognate target recognition of each Sib RNA by discriminating among non-cognate ibs mRNAs

RNA-Mediated Reciprocal Regulation between Two Bacterial Operons Is RNase III Dependent

In bacteria, RNAs regulate gene expression and function via several mechanisms. An RNA may pair with complementary sequences in a target RNA to impact transcription, translation, or degradation of the target. Control of conjugation of pCF10, a pheromone response plasmid of Enterococcus faecalis, is a well-characterized system that serves as a model for the regulation of gene expression in bacteria by intercellular signaling. The prgQ operon, whose products mediate conjugation, is negatively regulated by two products of the prgX operon, Anti-Q, a small RNA, and PrgX, the transcriptional repressor of the prgQ promoter. Here we show that Qs, an RNA from the 5′ end of the prgQ operon, represses expression of PrgX by targeting prgX mRNA for cleavage by RNase III. Our results demonstrate that the prgQ and prgX operons each use RNAs to negatively regulate gene expression from the opposing operon by different mechanisms. Such reciprocal regulation between two operons using RNAs has not been previously demonstrated. Furthermore, these results show that Qs is an unusually versatile RNA, serving three separate functions in the regulation of conjugation. Understanding the potential versatility of RNAs and their various roles in gene regulatory networks will allow us to better understand how cells regulate complex behavior

Genomic SELEX for Hfq-binding RNAs identifies genomic aptamers predominantly in antisense transcripts

An unexpectedly high number of regulatory RNAs have been recently discovered that fine-tune the function of genes at all levels of expression. We employed Genomic SELEX, a method to identify protein-binding RNAs encoded in the genome, to search for further regulatory RNAs in Escherichia coli. We used the global regulator protein Hfq as bait, because it can interact with a large number of RNAs, promoting their interaction. The enriched SELEX pool was subjected to deep sequencing, and 8865 sequences were mapped to the E. coli genome. These short sequences represent genomic Hfq-aptamers and are part of potential regulatory elements within RNA molecules. The motif 5′-AAYAAYAA-3′ was enriched in the selected RNAs and confers low-nanomolar affinity to Hfq. The motif was confirmed to bind Hfq by DMS footprinting. The Hfq aptamers are 4-fold more frequent on the antisense strand of protein coding genes than on the sense strand. They were enriched opposite to translation start sites or opposite to intervening sequences between ORFs in operons. These results expand the repertoire of Hfq targets and also suggest that Hfq might regulate the expression of a large number of genes via interaction with cis-antisense RNAs

Regulation of Enteric vapBC Transcription: Induction by VapC Toxin Dimer-Breaking

Toxin-antitoxin (TA) loci encode inhibitors of translation, replication or cell wall synthesis and are common elements of prokaryotic plasmids and chromosomes. Ten TA loci of Escherichia coli K-12 encode mRNases that cumulatively contribute to persistence (multidrug tolerance) of the bacterial cells. The mechanisms underlying induction and reversion of the persistent state are not yet understood. The vapBC operon of Salmonalla enterica serovar Typhimurium LT2 encodes VapC, a tRNase that reversibly inhibits translation by site-specific cleavage of tRNAfMet. VapB is an antitoxin that interacts with and neutralizes VapC via its C-terminal tail and regulate TA operon transcription via its N-terminal DNA binding domain that recognize operators in the vapBC promoter region. We show here that transcription of the vapBC operon of S. enterica is controlled by a recently discovered regulatory theme referred to as ‘conditional cooperativity’: at low T/A ratios, the TA complex binds cooperatively to the promoter region and represses TA operon transcription whereas at high T/A ratios, the excess toxin leads to destabilization of the TA-operator complex and therefore, induction of transcription. We present evidence that an excess of VapC toxin leads to operator complex destabilization by breaking of toxin dimers

Rfam: Wikipedia, clans and the “decimal” release

The Rfam database aims to catalogue non-coding RNAs through the use of sequence alignments and statistical profile models known as covariance models. In this contribution, we discuss the pros and cons of using the online encyclopedia, Wikipedia, as a source of community‐derived annotation. We discuss the addition of groupings of related RNA families into clans and new developments to the website. Rfam is available on the Web at http://rfam.sanger.ac.uk

Bacterial Toxin–Antitoxin Systems: More Than Selfish Entities?

Bacterial toxin–antitoxin (TA) systems are diverse and widespread in the prokaryotic kingdom. They are composed of closely linked genes encoding a stable toxin that can harm the host cell and its cognate labile antitoxin, which protects the host from the toxin's deleterious effect. TA systems are thought to invade bacterial genomes through horizontal gene transfer. Some TA systems might behave as selfish elements and favour their own maintenance at the expense of their host. As a consequence, they may contribute to the maintenance of plasmids or genomic islands, such as super-integrons, by post-segregational killing of the cell that loses these genes and so suffers the stable toxin's destructive effect. The function of the chromosomally encoded TA systems is less clear and still open to debate. This Review discusses current hypotheses regarding the biological roles of these evolutionarily successful small operons. We consider the various selective forces that could drive the maintenance of TA systems in bacterial genomes