Background: For pathogens which cause infections that present asymptomatically, evaluating vaccine efficacy (VE) against asymptomatic infection is important for understanding a vaccine's potential epidemiological impact. Regular testing for subclinical infections is a potentially valuable strategy but its success hinges on participant adherence and minimising false positives. This paper describes the implementation and adherence to weekly testing in a COVID-19 vaccine trial.
View Article and Find Full Text PDFBackground: Chronic nausea and vomiting syndromes (CNVS), gastroparesis and functional dyspepsia (FD) are complex disorders. Body Surface Gastric Mapping (BSGM), a new test of gastric function, using Gastric Alimetry® (Alimetry, New Zealand) may be useful for de-escalating healthcare utilisation. This study aimed to define healthcare costs and estimate health economic impacts of implementing this test in patients with chronic gastroduodenal symptoms.
View Article and Find Full Text PDFIntroduction: British military personnel deploy internationally to areas with high levels of ambient air pollution. Air pollution can cause acute respiratory symptoms which lead to concern about potential long-lasting health effects. There is a requirement for evidence-based policy on chronic respiratory disease associated with military deployments to areas with poor air quality (AQ).
View Article and Find Full Text PDFG3BP is the central node within stress-induced protein-RNA interaction networks known as stress granules (SGs). The SG-associated proteins Caprin-1 and USP10 bind mutually exclusively to the NTF2 domain of G3BP1, promoting and inhibiting SG formation, respectively. Herein, we present the crystal structure of G3BP1-NTF2 in complex with a Caprin-1-derived short linear motif (SLiM).
View Article and Find Full Text PDFCentrosomes are orbited by centriolar satellites, dynamic multiprotein assemblies nucleated by Pericentriolar material 1 (PCM1). To study the requirement for centriolar satellites, we generated mice lacking PCM1, a crucial component of satellites. mice display partially penetrant perinatal lethality with survivors exhibiting hydrocephalus, oligospermia, and cerebellar hypoplasia, and variably expressive phenotypes such as hydronephrosis.
View Article and Find Full Text PDFBackground: In May 2020, first-year students at Imperial College School of Medicine attended a 'digital hospital placement'. Occurring in the early months of the COVID-19 pandemic, this replaced their first planned hospital placement. The authors analysed student experiences to understand how a digital hospital placement impacted self-perceived clinical and professional development and whether it improved preparedness for face-to-face hospital placements.
View Article and Find Full Text PDFBackground: Malaria is a life-threatening disease. Prior to the pandemic, over a million people annually from non-endemic, high income countries such as Europe and North America visited countries with a risk of malaria transmission. Emergency care nurses in non-endemic countries frequently encounter returning travellers, presenting with symptoms suggestive of malaria.
View Article and Find Full Text PDFPurpose: This study aimed to measure the prevalence of menopausal symptoms in patients attending a multidisciplinary model of care clinic at their initial clinic visit and their subsequent follow-up consultation using a validated patient-reported outcome measure to assess whether menopausal symptoms after cancer had improved.
Methods: A retrospective review was conducted of patients attending the clinic in a 12-month period in 2017 (n = 189). Recorded variables included patient demographics, details of index cancer, previous treatments, and menopausal symptom management strategies.
Background: Phase III trials have estimated coronavirus disease 2019 (COVID-19) vaccine efficacy (VE) against symptomatic and asymptomatic infection. We explore the direction and magnitude of potential biases in these estimates and their implications for vaccine protection against infection and against disease in breakthrough infections.
Methods: We developed a mathematical model that accounts for natural and vaccine-induced immunity, changes in serostatus, and imperfect sensitivity and specificity of tests for infection and antibodies.
Stress granules (SGs) are dynamic RNA-protein complexes localized in the cytoplasm that rapidly form under stress conditions and disperse when normal conditions are restored. The formation of SGs depends on the Ras-GAP SH3 domain-binding protein (G3BP). Formations, interactions and functions of plant and human SGs are strikingly similar, suggesting a conserved mechanism.
View Article and Find Full Text PDFIdentification of the molecular networks that facilitated the evolution of multicellular animals from their unicellular ancestors is a fundamental problem in evolutionary cellular biology. Choanoflagellates are recognized as the closest extant nonmetazoan ancestors to animals. These unicellular eukaryotes can adopt a multicellular-like "rosette" state.
View Article and Find Full Text PDFObjective: Animal studies remain essential for understanding mechanisms of epilepsy and identifying new therapeutic targets. However, existing animal models of epilepsy do not reflect the high level of genetic diversity found in the human population. The Collaborative Cross (CC) population is a genetically diverse recombinant inbred panel of mice.
View Article and Find Full Text PDFRegulation by gene-distal enhancers is critical for cell type-specific and condition-specific patterns of gene expression. Thus, to understand the basis of gene activity in a given cell type or tissue, we must identify the precise locations of enhancers and functionally characterize their behaviors. Here, we demonstrate that transcription is a nearly universal feature of enhancers in and mammalian cells and that nascent RNA sequencing strategies are optimal for identification of both enhancers and superenhancers.
View Article and Find Full Text PDFThe Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users.
View Article and Find Full Text PDFStroke patients can experience a variety of pain. Many stroke patients have co-morbidities such as osteoporosis, arthritis or diabetes causing diabetic neuropathy. As well as pain from other long term conditions, stroke patients can experience central post-stroke pain, headaches, and musculoskeletal issues such as hypertonia, contractures, spasticity, and subluxations.
View Article and Find Full Text PDFIN AUGUST, the Nursing and Midwifery Council (NMC) concluded an 81-day hearing into care failings at Brithdir Care Home in Caerphilly, Wales. The hearing ended the UK's biggest inquiry into allegations of neglect to date. It led to three nurses being struck off, a fourth being suspended for one year and a fifth being given a caution order.
View Article and Find Full Text PDFPurpose: We sought to evaluate the relationship between the polycystic ovary syndrome (PCOS)-defining characteristics and the risk of developing metabolic complications in women presenting with complaints of infertility and/or menstrual irregularities and subsequently diagnosed with PCOS.
Methods: This was a cross-sectional study. Women presenting with complaints of infertility and/or irregular menses and diagnosed with PCOS by the Rotterdam criteria, underwent endocrine, metabolic, and ultrasound assessment in the early follicular phase.
The remarkable capacity for pluripotency and self-renewal in embryonic stem cells (ESCs) requires a finely tuned transcriptional circuitry wherein the pathways and genes that initiate differentiation are suppressed, but poised to respond rapidly to developmental signals. To elucidate transcriptional control in mouse ESCs in the naive, ground state, we defined the distribution of engaged RNA polymerase II (Pol II) at high resolution. We find that promoter-proximal pausing of Pol II is most enriched at genes regulating cell cycle and signal transduction and not, as expected, at developmental or bivalent genes.
View Article and Find Full Text PDFResearch on motivational climates consistently demonstrates that mastery-focused climates are associated with positive outcomes and ego-involving performance climates lead to maladaptive outcomes. However, the role of personality within such a framework has been largely ignored. To redress this imbalance, we examined the potential role of narcissism in moderating the effects of different motivational climates on leader-inspired extra effort in training.
View Article and Find Full Text PDF