Changes in CEBPB expression in circulating leukocytes following eccentric elbow-flexion exercise

This is the final version of the article. Available from Springer via the DOI in this record.In mouse models, CCAAT enhancer-binding protein beta (CEBPB) is necessary for M2 macrophage-mediated regeneration after muscle injury. In humans, CEBPB expression in blood was strongly associated with muscle strength. In this study we aimed to test whether CEBPB expression in blood in people is increased 2 days after exercise designed to induce muscle damage and subsequent repair. Sixteen healthy male volunteers undertook elbow flexor exercises designed to induce acute muscle micro-damage. Peripheral blood samples were collected at baseline and days 1, 2, 4 and 7 following exercise. Expression of CEBPB and related genes were analysed by qRT-PCR. Extent of muscle damage was determined by decline in maximal voluntary isometric torque and by plasma creatine kinase activity. Nine subjects had peak (day 4) creatine kinase activity exceeding 10,000 U/l. In this subgroup, CEBPB expression was elevated from baseline to 2 days post exercise (paired-samples t (1,8) = 3.72, p = 0.006). Related expression and selected cytokine changes after exercise did not reach significance. Muscle-damaging exercise in humans can be followed by induction of CEBPB transcript expression in peripheral blood. Associations between CEBPB expression in blood and muscle strength may be consistent with the CEBPB-dependent muscle repair process.Wellcome TrustNational Institute for Health Researc

A protocol for co-creating research project lay summaries with stakeholders:Guideline development for Canada's AGE-WELL Network

Background Funding bodies increasingly require researchers to write lay summaries to communicate projects’ real-world relevance to the public in an accessible way. However, research proposals and findings are generally not easily readable or understandable by non-specialist readers. Many researchers find writing lay summaries difficult because they typically write for fellow subject specialists or academics rather than the general public or a non-specialist audience. The primary objective of our project is to develop guidelines for researchers in Canada’s AGE-WELL Network of Centres of Excellence, and ultimately various other disciplines, sectors, and institutions, to co-create lay summaries of research projects with stakeholders. To begin, we produced a protocol for co-creating a lay summary based on workshops we organized and facilitated for an AGE-WELL researcher. This paper presents the lay summary co-creation protocol that AGE-WELL researchers will be invited to use. Methods Eligible participants in this project will be 24 AgeTech project researchers who are funded by the AGE-WELL network in its Core Research Program 2020. If they agree to participate in this project, we will invite them to use our protocol to co-produce a lay summary of their respective projects with stakeholders. The protocol comprises six steps: Investigate principles of writing a good lay summary, identify the target readership, identify stakeholders to collaborate with, recruit the identified stakeholders to work on a lay summary, prepare for workshop sessions, and execute the sessions. To help participants through the process, we will provide them with a guide to developing an accessible, readable research lay summary, help them make decisions, and host, and facilitate if needed, their lay summary co-creation workshops. Discussion Public-facing research outputs, including lay summaries, are increasingly important knowledge translation strategies to promote the impact of research on real-world issues. To produce lay summaries that include information that will interest a non-specialist readership and that are written in accessible language, stakeholder engagement is key. Furthermore, both researchers and stakeholders benefit by participating in the co-creation process. We hope the protocol helps researchers collaborate with stakeholders effectively to co-produce lay summaries that meet the needs of both the public and project funders

Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: Different boosting intervals and implications for efficacy trials

Objectives. To investigate the safety and immunogenicity of boosting BCG with modified vaccinia Ankara expressing antigen 85A (MVA85A), shortly after BCG vaccination, and to compare this first with the immunogenicity of BCG vaccination alone and second with a previous clinical trial where MVA85A was administered more than 10 years after BCG vaccination. Design. There are two clinical trials reported here: a Phase I observational trial with MVA85A; and a Phase IV observational trial with BCG. These clinical trials were all conducted in the UK in healthy, HIV negative, BCG naı¨ve adults. Subjects were vaccinated with BCG alone; or BCG and then subsequently boosted with MVA85A four weeks later (short interval). The outcome measures, safety and immunogenicity, were monitored for six months. The immunogenicity results from this short interval BCG prime–MVA85A boost trial were compared first with the BCG alone trial and second with a previous clinical trial where MVA85A vaccination was administered many years after vaccination with BCG. Results. MVA85A was safe and highly immunogenic when administered to subjects who had recently received BCG vaccination. When the short interval trial data presented here were compared with the previous long interval trial data, there were no significant differences in the magnitude of immune responses generated when MVA85A was administered shortly after, or many years after BCG vaccination. Conclusions. The clinical trial data presented here provides further evidence of the ability of MVA85A to boost BCG primed immune responses. This boosting potential is not influenced by the time interval between prior BCG vaccination and boosting with MVA85A. These findings have important implications for the design of efficacy trials with MVA85A. Boosting BCG induced anti-mycobacterial immunity in either infancy or adolescence are both potential applications for this vaccine, given the immunological data presented here. Trial Registration. ClinicalTrials.Oxford University was the sponsor for all the clinical trials reported here

Effects of a Tailored Follow-Up Intervention on Health Behaviors, Beliefs, and Attitudes

Background: The high rates of relapse that tend to occur after short-term behavioral interventions indicate the need for maintenance programs that promote long-term adherence to new behavior patterns. Computer-tailored health messages that are mailed to participants or given in brief telephone calls offer an innovative and time-efficient alternative to ongoing face-to-face contact with healthcare providers. Methods: Following a 1-year behavior change program, 22 North Carolina health departments were randomly assigned to a follow-up intervention or control condition. Data were collected from 1999 to 2001 by telephone-administered surveys at preintervention and postintervention for 511 low-income, midlife adult women enrolled in the Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) program at local North Carolina health departments. During the year after the behavior change program, intervention participants were mailed six sets of computer-tailored health messages and received two computer-tailored telephone counseling sessions. Main outcomes of dietary and physical activity behaviors, beliefs, and attitudes were measured. Results: Intervention participants were more likely to move forward into more advanced stages of physical activity change (p = 0.02); control participants were more likely to increase their level of dietary social support at follow-up (p = 0.05). Both groups maintained low levels of reported saturated fat and cholesterol intake at follow-up. No changes were seen in physical activity in either group. Conclusions: Mailed computer-tailored health messages and telephone counseling calls favorably modified forward physical activity stage movement but did not appreciably affect any other psychosocial or behavioral outcomes

Effectiveness of a simple lymphoedema treatment regimen in podoconiosis management in southern Ethiopia: one year follow-up

Background: Podoconiosis is a non-filarial elephantiasis caused by long-term barefoot exposure to volcanic soils in endemic areas. Irritant silicate particles penetrate the skin, causing a progressive, debilitating lymphoedema of the lower leg, often starting in the second decade of life. A simple patient-led treatment approach appropriate for resource poor settings has been developed, comprising (1) education on aetiology and prevention of podoconiosis, (2) foot hygiene (daily washing with soap, water and an antiseptic), (3) the regular use of emollient, (4) elevation of the limb at night, and (5) emphasis on the consistent use of shoes and socks. Methodology/Principal Findings: We did a 12-month, non-comparative, longitudinal evaluation of 33 patients newly presenting to one clinic site of a non-government organization (the Mossy Foot Treatment & Prevention Association, MFTPA) in southern Ethiopia. Outcome measures used for the monitoring of disease progress were (1) the clinical staging system for podoconiosis, and (2) the Amharic Dermatology Life Quality Index (DLQI), both of which have been recently validated for use in this setting. Digital photographs were also taken at each visit. Twenty-seven patients completed follow up. Characteristics of patients completing follow-up were not significantly different to those not. Mean clinical stage and lower leg circumference decreased significantly (mean difference -0.67 (95% CI -0.38 to -0.96) and -2.00 (95% CI -1.26 to -2.74), respectively, p<0.001 for both changes). Mean DLQI diminished from 21 (out of a maximum of 30) to 6 (p<0.001). There was a non-significant change in proportion of patients with mossy lesions (p = 0.375). Conclusions/Significance: This simple, resource-appropriate regimen has a considerable impact both on clinical progression and self-reported quality of life of affected individuals. The regimen appears ideal for scaling up to other endemic regions in Ethiopia and internationally. We recommend that further research in the area include analysis of cost-effectiveness of the regimen

HIV-1 is dependent on its immature lattice to recruit IP6 for mature capsid assembly

HIV-1 Gag metamorphoses inside each virion, from an immature lattice that forms during viral production to a mature capsid that drives infection. Here we show that the immature lattice is required to concentrate the cellular metabolite inositol hexakisphosphate (IP6) into virions to catalyze mature capsid assembly. Disabling the ability of HIV-1 to enrich IP6 does not prevent immature lattice formation or production of the virus. However, without sufficient IP6 molecules inside each virion, HIV-1 can no longer build a stable capsid and fails to become infectious. IP6 cannot be replaced by other inositol phosphate (IP) molecules, as substitution with other IPs profoundly slows mature assembly kinetics and results in virions with gross morphological defects. Our results demonstrate that while HIV-1 can become independent of IP6 for immature assembly, it remains dependent upon the metabolite for mature capsid formation

Carer subjective burden after first-episode psychosis: Types and predictors. A multilevel statistical approach

Background: Carer burden at first-episode psychosis is common and adds to the multiple other psychiatric and psychological problems that beset new carers; yet, knowledge of the factors that predict carer burden is limited. Aim: This study sought to investigate the types and predictors of carer burden at first-episode psychosis in the largest, most ethnically diverse and comprehensively characterised sample to date. Method: This study involved a cross-sectional survey of carers of people with first-episode psychosis presenting to Harrow and Hillingdon Early Intervention in Psychosis service between 2011 and 2017. Carers completed self-report measures assessing their illness beliefs, coping styles and caregiving experiences (i.e. burden). Thirty carer and patient sociodemographic and clinical factors were also collected. Mixed effects linear regression modelling was conducted to account for clustering of carers by patient, with carer burden (and its 8 subtypes) investigated as dependent variables. Results: The sample included data on 254 carers (aged 18–74 years) and 198 patients (aged 14–36 years). Regression modelling identified 35 significant predictors of carer burden and its subtypes at first-episode psychosis. Higher total burden was independently predicted by perceiving greater negative consequences of the illness for the patient (B = .014, p < .001, 95% CI: [.010–.018]) and the carer (B = .008, p = .002, 95% CI: [.003–.013]), and engaging in avoidant-focussed coping (B = .010, p = .006, 95% CI: [.003–.016]). Lower burden was independently predicted by patients being in a relationship (B = −.075, p = .047, 95% CI: [−.149 to −.001]). Predictors of the eight burden subtypes (difficult behaviours, negative symptoms, stigma, problems with services, effects on family, dependency, loss and need to backup) are also included in the article. Conclusion: Findings can be used to inform the identification of carers ‘at-risk’ of experiencing burden and highlight potential targets for theraputic intervention to lower carer buden

Obstetric anal sphincter injury: a systematic review of information available on the internet.

OBJECTIVE: There is no systematic evaluation of online health information pertaining to obstetric anal sphincter injury. Therefore, we evaluated the accuracy, credibility, reliability, and readability of online information concerning obstetric anal sphincter injury. MATERIALS AND METHODS: Multiple search engines were searched. The first 30 webpages were identified for each keyword and considered eligible if they provided information regarding obstetric anal sphincter injury. Eligible webpages were assessed by two independent researchers for accuracy (prioritised criteria based upon the RCOG Third and Fourth Degree Tear guideline); credibility; reliability; and readability. RESULTS: Fifty-eight webpages were included. Seventeen webpages (30%) had obtained Health On the Net certification, or Information Standard approval and performed better than those without such approvals (p = 0.039). The best overall performing website was http://www.pat.nhs.uk (score of 146.7). A single webpage (1%) fulfilled the entire criteria for accuracy with a score of 18: www.tamesidehospital.nhs.uk . Twenty-nine webpages (50%) were assessed as credible (scores ≥7). A single webpage achieved a maximum credibility score of 10: www.meht.nhs.uk . Over a third (21 out of 58) were rated as poor or very poor. The highest scoring webpage was http://www.royalsurrey.nhs.uk (score 62). No webpage met the recommended Flesch Reading Ease Score above 70. The intra-class coefficient between researchers was 0.98 (95% CI 0.96-0.99) and 0.94 (95% CI 0.89-0.96) for accuracy and reliability assessments. CONCLUSION: Online information concerning obstetric anal sphincter injury often uses language that is inappropriate for a lay audience and lacks sufficient accuracy, credibility, and reliability