127 research outputs found

    Characterisation of infection associated microRNA and protein cargo in extracellular vesicles of Theileria annulata infected leukocytes

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    The protozoan parasites, Theileria annulata and T. parva are unique amongst intracellular eukaryotic pathogens as they induce a transformation‐like phenotype in their bovine host cell. T. annulata causes tropical theileriosis, which is frequently fatal, with infected leukocytes becoming metastatic and forming foci in multiple organs resulting in destruction of the lymphoid system. Exosomes, a sub‐set of extracellular vesicles (EV), are critical in metastatic progression in many cancers. Here we characterised the cargo of EV from a control bovine lymphosarcoma cell line (BL20) and BL20 infected with T. annulata (TBL20) by comparative mass spectrometry and miRNA profiling (data available via ProteomeXchange, identifier PXD010713 and NCBI GEO, accession number GSE118456, respectively). Ingenuity Pathway Analysis that many infection‐associated proteins essential to migration and extracellular matrix digestion were upregulated in EV from TBL20 cells compared to BL20 controls. An altered repertoire of host miRNA, many with known roles in tumor and/or infection biology was also observed. Focusing on the tumor suppressor miRNA, bta‐miR‐181a and bta‐miR‐181b, we identified putative mRNA targets and confirmed the interaction of bta‐miR181a with icam‐1. We propose that EV and their miRNA cargo play an important role in the manipulation of the host cell phenotype and the pathobiology of Theileria infection

    Rapid recovery following short-term acoustic disturbance in two fish species

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    ArticleNoise from human activities is known to impact organisms in a variety of taxa, but most experimental studies on the behavioural effects of noise have focused on examining responses associated with the period of actual exposure. Unlike most pollutants, acoustic noise is generally short-lived, usually dissipating quickly after the source is turned off or leaves the area. In a series of experiments, we use established experimental paradigms to examine how fish behaviour and physiology are affected, both during short-term (2 min) exposure to playback of recordings of anthropogenic noise sources and in the immediate aftermath of noise exposure. We considered the anti-predator response and ventilation rate of juvenile European eels (Anguilla anguilla), and ventilation rate of juvenile European seabass (Dicentrarchus labrax). As previously found, additional-noise exposure decreased eel anti-predator responses, increased startle latency and increased ventilation rate relative to ambient-noise-exposed controls. Our results show for the first time that those effects quickly dissipated; eels showed rapid recovery of startle responses and startle latency, and rapid albeit incomplete recovery of ventilation rate in the 2 min after noise cessation. Seabass in both laboratory and open-water conditions showed an increased ventilation rate during playback of additional noise compared to ambient conditions. However, within 2 min of noise cessation, ventilation rate showed complete recovery to levels equivalent to ambient-exposed control individuals. Care should be taken in generalizing these rapid-recovery results, as individuals might have accrued other costs during noise exposure and other species might show different recovery times. Nonetheless, our results from two different fish species provide tentative cause for optimism concerning recovery following short-duration noise exposure, and suggest that considering periods following noise exposures could be important for mitigation and management decisions.DefraNER

    Investigation into the effect of skin tone modulators and exogenous stress on skin pigmentation utilizing a novel bioengineered skin equivalent

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    Human skin equivalents (HSEs) are a popular technology due to limitations in animal testing, particularly as they recapitulate aspects of structure and function of human skin. Many HSEs contain two basic cell types to model dermal and epidermal compartments, however this limits their application, particularly when investigating the effect of exogenous stressors on skin health. We describe the development of a novel platform technology that accurately replicates skin pigmentation in vitro. Through incorporation of melanocytes, specialized pigment producing cells, into the basal layer of the epidermis we are able to re-create skin pigmentation in vitro. We observe apical distribution of melanin within keratinocytes and formation of supranuclear caps (SPNCs), only when the epidermal compartment is co-cultured with a dermal compartment, leading to the conclusion that fibroblast support is essential for correct pigment organization. We also evaluate the commonly observed phenomenon that pigmentation darkens with time in vitro, which we further explore through mechanical exfoliation to remove a build-up of melanin deposits in the stratum corneum. Finally, we demonstrate the application of a pigmented HSE to investigate drug modulation of skin tone and protection from UV-induced damage, highlighting the importance of such a model in the wider context of skin biology

    Europeanization of sub-arctic environments : perspectives from Norse Greenland's outer fjords

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    Acknowledgements The authors gratefully acknowledge the financial support of the Leverhulme Trust Footprints on the Edge of Thule Programme Award. ECL acknowledges the support of the Weissman International Internship Program, the Department of Earth and Planetary Sciences and the Department of Anthropology at Harvard. We would also like to thank George McLeod (University of Stirling) for manufacturing soil thin sections.Peer reviewedPostprin

    Living with and without an intestinal stoma: Factors that promote psychological well-being and self-care: A cross sectional study.:Psychological well-being and stoma

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    Abstract Aims This study compared those living with and without an intestinal stoma in relation to physical and psychological health, stress and coping, quality of life and resilience. Also, identifying factors that could be used to promote better self‐care in stoma patients in the future. Design A cross‐sectional and comparative study design was employed. Methods Participants were recruited via email and social media (Facebook and Twitter) between August 2018 and March 2019, to complete an online survey. The data were analysed using analysis of variance to examine group difference and a series of hierarchical linear regression analyses determining predictors of psychological well‐being. Results Of 278 participants aged 18–68 years who completed the survey, 129 (46%) had a stoma and reported significantly poorer physical health. Approximately one‐fifth experienced problems with stoma management. Psychological well‐being was mediated by the duration of living with a stoma (under 3 years) and frequency of leaks (weekly and monthly)

    Evolution of Ostomy Pouch Design: Opportunities for Composite Technologies to Advance Patient Care

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    Stoma surgery can be critical in helping to restore the well-being of patients sufferingfrom gastrointestinal disease or injury but it inevitably comes with numerous psychological andphysiological complications. Disposable pouch systems which enable the collection of bowel wastehave revolutionized stoma care but providing robust, discreet devices that can efficiently meet therequirements of the patient can be challenging. Pouches must securely store a microbially active wastewhilst preventing leakage, protecting the underlying skin from inflammation and minimizing odor.All of this needs to be achieved within the design constraints of a pouch that is easy to manage andyet still maintains a discreet body contour. Stoma collection has moved from the waste being collectedin butyl rubber pouches to much more elaborate systems incorporating assemblies of polyvinylidenechloride, ethylene vinyl acetate, ethyl vinyl alcohol and polyvinyl alcohol with new, skin-friendlyadhesive such as hydrocolloid and silicones impregnated with ceramides and aloe. Moreover, 3Dprinting has emerged as a means of providing personalized stoma pouches that can potentiallyaddress the age-old issue of leakage. Despite such advances, stoma pouches have evolved slowlyover the past 70 or so years. A survey of the literature reveals an abundance of quality-of-life studiesbut a dearth of reports addressing the key technological challenges. Consequently, this narrativereview considers current stoma pouch technology and highlights the issues that continue to afflictstoma patients. Research and patent literature is critically appraised in terms of current pouchtechnology and the potential opportunities for new composite materials are identified

    A peer-led intervention to promote sexual health in secondary schools: the STASH feasibility study

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    Background: Young people report higher levels of unsafe sex and have higher rates of sexually transmitted infections than any other age group. Schools are well placed to facilitate early intervention, but more effective approaches are required. Peer-led approaches can augment school-based education, but often fail to capitalise on mechanisms of social influence. The potential of using social media in sexual health has not been tested in school settings. Objectives: Finalise the design of the Sexually Transmitted infections And Sexual Health (STASH) intervention; assess the recruitment and retention of peer supporters, and acceptability to participants and stakeholders; assess the fidelity and reach, in addition to the barriers to and facilitators of, implementation; refine programme theory; understand the potential of social media; determine design parameters for a future randomised controlled trial, including economic evaluation; and establish whether or not progression criteria were met. Design: This was a feasibility study comprising intervention development and refinement of the STASH pilot and non-randomised feasibility trial in six schools. Control data were provided by students in the year above the intervention group. Setting: Secondary schools in Scotland. Participants: Students aged 14–16 years, teachers and intervention delivery partners. Interventions: The STASH intervention was adapted from A Stop Smoking In Schools Trial (ASSIST) (an effective peer-led smoking intervention). Based on diffusion of innovation theory, the STASH study involves peer nomination to identify the most influential students, with the aim of recruiting and training 15% of the year group as peer supporters. The peer supporters deliver sexual health messages to friends in their year group via conversations and use of Facebook (www.facebook.com; Facebook, Inc., Menlo Park, CA, USA) to share varied content from a curated set of web-based resources. Peer supporters are given support themselves via follow-up sessions and via trainer membership of Facebook groups. Main outcome measures: The primary outcome was whether or not progression criteria were met in relation to intervention acceptability and feasibility. The study also piloted indicative primary outcomes for a full-scale evaluation. Data sources: Peer supporter questionnaire; observations of activities; interviews with trainers, teachers, peer supporters and students; monitoring log of peer supporter activities (including on Facebook and meeting attendance); questionnaire to control year group (baseline characteristics, social networks, mediators and sexual health outcomes); baseline and follow-up questionnaire (approximately 6 months later) for intervention year group. Results: A total of 104 students were trained as peer supporters (just over half of those nominated for the role by their peers). Role retention was very high (97%). Of 611 students completing the follow-up questionnaire, 58% reported exposure to STASH study activities. Intervention acceptability was high among students and stakeholders. Activities were delivered with good fidelity. The peer supporters were active, representative of their year group and well connected within their social network. Carefully managed social media use by peer supporters augmented conversations. A primary outcome of ‘always safer sex’ was identified, measured as no sex or always condom use for vaginal or anal sex in the last 6 months. The intervention cost £42 per student. Six progression criteria were met. A seventh criterion (regarding uptake of role by peer supporters) was not. Limitations: Small feasibility study that cannot comment on effectiveness. Conclusions: The STASH intervention is feasible and acceptable within the context of Scottish secondary schools. The results support continuation to a full-scale evaluation. Future work: Small-scale improvements to the intervention, refinement to programme theory and funding sought for full-scale evaluation. Trial registration Current Controlled Trials ISRCTN97369178. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 8, No. 15. See the NIHR Journals Library website for further project information

    Evaluation of SARS-CoV-2 antibody point of care devices in the laboratory and clinical setting

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    SARS-CoV-2 antibody tests have been marketed to diagnose previous SARS-CoV-2 infection and as a test of immune status. There is a lack of evidence on the performance and clinical utility of these tests. We aimed to carry out an evaluation of 14 point of care (POC) SARS-CoV-2 antibody tests. Serum from participants with previous RT-PCR (real-time polymerase chain reaction) confirmed SARS-CoV-2 infection and pre-pandemic serum controls were used to determine specificity and sensitivity of each POC device. Changes in sensitivity with increasing time from infection were determined on a cohort of study participants. Corresponding neutralising antibody status was measured to establish whether the detection of antibodies by the POC device correlated with immune status. Paired capillary and serum samples were collected to ascertain whether POC devices performed comparably on capillary samples. Sensitivity and specificity varied between the POC devices and in general did not meet the manufacturers’ reported performance characteristics, which signifies the importance of independent evaluation of these tests. The sensitivity peaked at ≥20 days following onset of symptoms, however sensitivity of 3 of the POC devices evaluated at extended time points showed that sensitivity declined with time. This was particularly marked at >140 days post infection. This is relevant if the tests are to be used for sero-prevalence studies. Neutralising antibody data showed that positive antibody results on POC devices did not necessarily confer high neutralising antibody titres, and that these POC devices cannot be used to determine immune status to the SARS-CoV-2 virus. Comparison of paired serum and capillary results showed that there was a decline in sensitivity using capillary blood. This has implications in the utility of the tests as they are designed to be used on capillary blood by the general population
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