Caroline Lee

The prehospital management of pelvic fractures

Pelvic fractures are one of the potentially life-threatening injuries that should be identified during the primary survey in patients sustaining major trauma. Early suspicion, identification and management of a pelvic fracture at the prehospital stage is essential to reduce the risk of death as a result of hypovolaemia and to allow appropriate triage of the patient. The assessment and management of pelvic fractures in the prehospital environment is reviewed here. It is advocated that the pelvis should not be examined by palpation or springing, and that the patient should not be log rolled. Pelvic immobilisation should be used routinely if there is any suspicion of pelvic fracture based on the mechanism of injury, symptoms and clinical findings.

PRMT5 Protects Genomic Integrity during Global DNA Demethylation in Primordial Germ Cells and Preimplantation Embryos

Summary Primordial germ cells (PGCs) and preimplantation embryos undergo epigenetic reprogramming, which includes comprehensive DNA demethylation. We found that PRMT5, an arginine methyltransferase, translocates from the cytoplasm to the nucleus during this process. Here we show that conditional loss of PRMT5 in early PGCs causes complete male and female sterility, preceded by the upregulation of LINE1 and IAP transposons as well as activation of a DNA damage response. Similarly, loss of maternal-zygotic PRMT5 also leads to IAP upregulation. PRMT5 is necessary for the repressive H2A/H4R3me2s chromatin modification on LINE1 and IAP transposons in PGCs, directly implicating this modification in transposon silencing during DNA hypomethylation. PRMT5 translocates back to the cytoplasm subsequently, to participate in the previously described PIWI-interacting RNA (piRNA) pathway that promotes transposon silencing via de novo DNA remethylation. Thus, PRMT5 is directly involved in genome defense during preimplantation development and in PGCs at the time of global DNA demethylation.

Chromatin dynamics and the role of G9a in gene regulation and enhancer silencing during early mouse development

Early mouse development is accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2), which is essential for embryonic development. Here we show that genome-wide accumulation of H3K9me2 is crucial for postimplantation development, and coincides with redistribution of enhancer of zeste homolog 2 (EZH2)-dependent histone H3 lysine 27 trimethylation (H3K27me3). Loss of G9a or EZH2 results in upregulation of distinct gene sets involved in cell cycle regulation, germline development and embryogenesis. Notably, the H3K9me2 modification extends to active enhancer elements where it promotes developmentally-linked gene silencing and directly marks promoters and gene bodies. This epigenetic mechanism is important for priming gene regulatory networks for critical cell fate decisions in rapidly proliferating postimplantation epiblast cells. DOI: http://dx.doi.org/10.7554/eLife.09571.001

The prehospital management of chest injuries: a consensus statement. Faculty of Pre-hospital Care, Royal College of Surgeons of Edinburgh

This paper provides a guideline for the management of prehospital chest injuries after a consensus meeting held by the Faculty of Prehospital Care, Royal College of Surgeons of Edinburgh, Edinburgh, UK, in January 2005. An overview of the prehospital assessment, diagnosis and interventions for life threatening chest injury are discussed, with the application of skills depending on the training, experience and competence of the individual practitioner.

Stella modulates transcriptional and endogenous retrovirus programs during maternal-to-zygotic transition

The maternal-to-zygotic transition (MZT) marks the period when the embryonic genome is activated and acquires control of development. Maternally inherited factors play a key role in this critical developmental process, which occurs at the 2-cell stage in mice. We investigated the function of the maternally inherited factor Stella (encoded by Dppa3) using single-cell/embryo approaches. We show that loss of maternal Stella results in widespread transcriptional mis-regulation and a partial failure of MZT. Strikingly, activation of endogenous retroviruses (ERVs) is significantly impaired in Stella maternal/zygotic knockout embryos, which in turn leads to a failure to upregulate chimeric transcripts. Amongst ERVs, MuERV-L activation is particularly affected by the absence of Stella, and direct in vivo knockdown of MuERV-L impacts the developmental potential of the embryo. We propose that Stella is involved in ensuring activation of ERVs, which themselves play a potentially key role during early development, either directly or through influencing embryonic gene expression. DOI: http://dx.doi.org/10.7554/eLife.22345.001

Unplanned, urgent and emergency care: what are the roles that EMS plays in providing for older people with dementia? An integrative review of policy, professional recommendations and evidence

Objective To synthesise the existing literature on the roles that emergency medical services (EMS) play in unplanned, urgent and emergency care for older people with dementia (OPWD), to define these roles, understand the strength of current research and to identify where the focus of future research should lie. Design An integrative review of the synthesised reports, briefings, professional recommendations and evidence. English-language articles were included if they made any reference to the role of EMS in the urgent or emergency care of OPWD. Preparatory scoping and qualitative work with frontline ambulance and primary care staff and carers of OPWD informed our review question and subsequent synthesis. Results Seventeen literature sources were included. Over half were from the grey literature. There was no research that directly addressed the review question. There was evidence in reports, briefings and professional recommendations of EMS addressing some of the issues they face in caring for OPWD. Three roles of EMS could be drawn out of the literature: emergency transport, assess and manage and a ‘last resort’ or safety net role. Conclusions The use of EMS by OPWD is not well understood, although the literature reviewed demonstrated a concern for this group and awareness that services are not optimum. Research in dementia care should consider the role that EMS plays, particularly if considering crises, urgent care responses and transitions between care settings. EMS research into new ways of working, training or extended paramedical roles should consider specific needs and challenges of responding to people with dementia.

Rectal or intravenous non-steroidal anti-inflammatory drugs in acute renal colic

A short cut review was carried out to establish whether rectal non-steroidal anti-inflammatory drugs (NSAIDs) are as effective as IV NSAIDs in the management of acute renal colic. Altogether 179 papers were found using the reported search, of which two represent the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. Rectal NSAIDs are an effective form of analgesia for patients with acute renal colic and have fewer side effects compared with intravenous NSAIDs.

Aspirin in the treatment of acute pulmonary embolism

A short cut review was carried out to establish whether aspirin is a useful adjunct in the treatment of acute pulmonary embolism. No papers were found using the reported search to answer the clinical question. A clinical bottom line is stated.

G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

Early mouse development is regulated and accompanied by dynamic changes in chromatin modifications, including G9a-mediated histone H3 lysine 9 dimethylation (H3K9me2). Previously, we provided insights into its role in post-implantation development (Zylicz et al., 2015). Here we explore the impact of depleting the maternally inherited G9a in oocytes on development shortly after fertilisation. We show that G9a accumulates typically at 4 to 8 cell stage to promote timely repression of a subset of 4 cell stage-specific genes. Loss of maternal inheritance of G9a disrupts the gene regulatory network resulting in developmental delay and destabilisation of inner cell mass lineages by the late blastocyst stage. Our results indicate a vital role of this maternally inherited epigenetic regulator in creating conducive conditions for developmental progression and on cell fate choices.

SRSF3 maintains transcriptome integrity in oocytes by regulation of alternative splicing and transposable elements

The RNA-binding protein SRSF3 (also known as SRp20) has critical roles in the regulation of pre-mRNA splicing. Zygotic knockout of Srsf3 results in embryo arrest at the blastocyst stage. However, SRSF3 is also present in oocytes, suggesting that it might be critical as a maternally inherited factor. Here we identify SRSF3 as an essential regulator of alternative splicing and of transposable elements to maintain transcriptome integrity in mouse oocyte. Using 3D time-lapse confocal live imaging, we show that conditional deletion of Srsf3 in fully grown germinal vesicle oocytes substantially compromises the capacity of germinal vesicle breakdown (GVBD), and consequently entry into meiosis. By combining single cell RNA-seq, and oocyte micromanipulation with steric blocking antisense oligonucleotides and RNAse-H inducing gapmers, we found that the GVBD defect in mutant oocytes is due to both aberrant alternative splicing and derepression of B2 SINE transposable elements. Together, our study highlights how control of transcriptional identity of the maternal transcriptome by the RNA-binding protein SRSF3 is essential to the development of fertilized-competent oocytes.