Histone H3.3 and its proteolytically processed form drive a cellular senescence programme.

The process of cellular senescence generates a repressive chromatin environment, however, the role of histone variants and histone proteolytic cleavage in senescence remains unclear. Here, using models of oncogene-induced and replicative senescence, we report novel histone H3 tail cleavage events mediated by the protease Cathepsin L. We find that cleaved forms of H3 are nucleosomal and the histone variant H3.

Percutaneous coronary intervention causes a rapid but transient mobilisation of CD34(+)CD45(-) cells.

Objective: Circulating CD34(+)CD45(-) cell concentrations are increased in patients with coronary artery disease, however their pathophysiological significance is unknown. We determined CD34(+)CD45(-) cell concentrations following percutaneous coronary intervention (PCI) in order to explore their role in acute vascular injury.

Methods: In a prospective time-course analysis, we quantified using flow cytometry circulating CD34(+)CD45(-) cells, traditional CD34(+)VEGFR-2(+) putative endothelial progenitor cells (EPCs), CD14(+) VEGFR(-) 2(+)Tie-2(+) angiogenic monocytes and intercellular adhesion molecule expression (CXCR-4 and CD18) in patients, before and during the first week following diagnostic angiography (n=13) or PCI (n=23).

iMSAT: a novel approach to the development of microsatellite loci using barcoded Illumina libraries.

Background: Illumina sequencing with its high number of reads and low per base pair cost is an attractive technology for development of molecular resources for non-model organisms. While many software packages have been developed to identify short tandem repeats (STRs) from next-generation sequencing data, these methods do not inform the investigator as to whether or not candidate loci are polymorphic in their target populations.

Results: We provide a python program iMSAT that uses the polymorphism data obtained from mapping individual Illumina sequence reads onto a reference genome to identify polymorphic STRs.

What is behind the ear drum? The microbiology of otitis media and the nasopharyngeal flora in children in the era of pneumococcal vaccination.

Aim: This study aims to describe the microbiology of middle ear fluid (MEF) in a cohort of children vaccinated with Streptococcus pneumoniae conjugate vaccine (PCV7) having ventilation tube insertion. Nasopharyngeal (NP) carriage of otopathogens in these children is compared with children without history of otitis media.

Methods: Between May and November 2011, MEF and NP samples from 325 children aged <3 years were collected in three major centres in New Zealand at the time of ventilation tube insertion.

Stress hyperglycaemia in hospitalised patients and their 3-year risk of diabetes: a Scottish retrospective cohort study.

Background: Hyperglycaemia during hospital admission is common in patients who are not known to have diabetes and is associated with adverse outcomes. The risk of subsequently developing type 2 diabetes, however, is not known. We linked a national database of hospital admissions with a national register of diabetes to describe the association between admission glucose and the risk of subsequently developing type 2 diabetes.

Training recruiters to randomized trials to facilitate recruitment and informed consent by exploring patients' treatment preferences.

Background: Patients' treatment preferences are often cited as barriers to recruitment in randomized controlled trials (RCTs). We investigated how RCT recruiters reacted to patients' treatment preferences and identified key strategies to improve informed decision-making and trial recruitment.

Methods: Audio-recordings of 103 RCT recruitment appointments with 96 participants in three UK multicenter pragmatic RCTs were analyzed using content and thematic analysis.

You are what you eat: fatty acid profiles as a method to track the habitat movement of an insect.

Tracking the movement of small organisms is of tremendous importance to understanding the ecology of populations, communities, and ecosystems. However, it remains one of the most difficult challenges facing the field of movement ecology. We developed an intrinsic marking technique for tracking small organisms using dietary fatty acid profiles as a biomarker as well as for clarifying source-sink dynamics between populations on a landscape level.

High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis.

Aims: High-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome.

Methods And Results: Plasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay.

The importance of individual developmental variation in stage-structured population models.

Population stage structure is fundamental to ecology, and models of this structure have proven useful in many different systems. Many ecological variables other than stage, such as habitat type, site occupancy and metapopulation status are also modelled using transitions among discrete states. Transitions among life stages can be characterised by the distribution of time spent in each stage, including the mean and variance of each stage duration and within-individual correlations among multiple stage durations.

Controlled exposures to air pollutants and risk of cardiac arrhythmia.

Background: Epidemiological studies have reported associations between air pollution exposure and increases in cardiovascular morbidity and mortality. Exposure to air pollutants can influence cardiac autonomic tone and reduce heart rate variability, and may increase the risk of cardiac arrhythmias, particularly in susceptible patient groups.

Objectives: We investigated the incidence of cardiac arrhythmias during and after controlled exposure to air pollutants in healthy volunteers and patients with coronary heart disease.

Time to be BRAVE: is educating surgeons the key to unlocking the potential of randomised clinical trials in surgery? A qualitative study.

Background: Well-designed randomised clinical trials (RCTs) provide the best evidence to inform decision-making and should be the default option for evaluating surgical procedures. Such trials can be challenging, and surgeons' preferences may influence whether trials are initiated and successfully conducted and their results accepted. Preferences are particularly problematic when surgeons' views play a key role in procedure selection and patient eligibility.

Mevalonate deprivation mediates the impact of lovastatin on the differentiation of murine 3T3-F442A preadipocytes.

The statins competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and consequently the synthesis of mevalonate. The use of statins is associated with insulin resistance, presumably due to the impaired differentiation and diminished glucose utilization of adipocytes. We hypothesize that mevalonate is essential to adipocyte differentiation and adipogenic gene expression.

Comparing specialist medical care with specialist medical care plus the Lightning Process for chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME): study protocol for a randomised controlled trial (SMILE Trial).

Background: Chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) is a relatively common and potentially serious condition with a limited evidence base for treatment. Specialist treatment for paediatric CFS/ME uses interventions recommended by National Institute for Health and Clinical Excellence (NICE) including cognitive behavioural therapy, graded exercise therapy and activity management. The Lightning Process (LP) is a trademarked intervention derived from osteopathy, life-coaching and neuro-linguistic programming, delivered over three consecutive days as group sessions.

Diesel exhaust particulate increases the size and complexity of lesions in atherosclerotic mice.

Objective: Diesel exhaust particulate (DEP), a major component of urban air pollution, has been linked to atherogenesis and precipitation of myocardial infarction. We hypothesized that DEP exposure would increase and destabilise atherosclerotic lesions in apolipoprotein E deficient (ApoE-/-) mice.

Methods: ApoE-/- mice were fed a 'Western diet' (8 weeks) to induce 'complex' atherosclerotic plaques, with parallel experiments in normal chow fed wild-type mice.

The feasibility and acceptability of conducting a trial of specialist medical care and the Lightning Process in children with chronic fatigue syndrome: feasibility randomized controlled trial (SMILE study).

Background: Chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME) is relatively common in children with limited evidence for treatment. The Phil Parker Lightning Process (LP) is a trademarked intervention, which >250 children use annually. There are no reported studies investigating the effectiveness or possible side effects of LP.

Moderate level exposure to magnetic nanodots encased in tunable poly(ethylene glycol) analouge biopolymer shell do not deleteriously affect neurite outgrowth.

Recently, huge interest has been generated in investigating the possible therapeutic use of tunable magnetic nanostructures to overcome the existing challenges to treat central nervous system damage related conditions. However, several issues (e.g.

Inspiratory muscle training for cystic fibrosis.

Background: Cystic fibrosis is the most common life-limiting genetic condition in Caucasians and the life-expectancy of those newly diagnosed is increasing. Inspiratory muscle training may be a way of improving the lung function and quality of life of people with cystic fibrosis. Hence there is a need to establish whether this intervention is beneficial.

18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial.

Background: The use of non-invasive imaging to identify ruptured or high-risk coronary atherosclerotic plaques would represent a major clinical advance for prevention and treatment of coronary artery disease. We used combined PET and CT to identify ruptured and high-risk atherosclerotic plaques using the radioactive tracers (18)F-sodium fluoride ((18)F-NaF) and (18)F-fluorodeoxyglucose ((18)F-FDG).

Methods: In this prospective clinical trial, patients with myocardial infarction (n=40) and stable angina (n=40) underwent (18)F-NaF and (18)F-FDG PET-CT, and invasive coronary angiography.

Endothelial progenitor cells in patients with chronic obstructive pulmonary disease.

The pathogenesis of chronic obstructive pulmonary disease is not fully understood. The objective of this study was to compare circulating endothelial progenitor cells in patients with chronic obstructive pulmonary disease to age, sex, and cigarette smoking matched healthy controls. Patients with chronic obstructive pulmonary disease (n = 37) and healthy controls (n = 19) were matched by age, sex, and smoking status.

Early healing and hearing improvement following type one tympanoplasty using the 'drum sandwich' technique.

Background: The results of a number of tympanic membrane perforation closure techniques have been reported. However, relatively little has been published on the 'drum sandwich' technique.

Method: Retrospective chart review of 123 patients undergoing type one tympanoplasty, performed by one surgeon using the drum sandwich technique.