• Cognitive function and disability in late Life: An ecological validation of the 10/66 battery of cognitive tests among community dwelling older adults in south India

      Krishna, Murali; Beulah, Eunice; Jones, Steven; Sundaracharj, Rajesh; Saroja, A.; Kumaran, Kalyanaraman; Karat, Samuel C.; Prince, Martin; Fall, Caroline H. D.; University of Chester (Wiley, 2015-12-17)
      Key Points • 10/66 cognitive tests are well suited for identification of older adults with cognitive and functional impairment at a population level in LMIC setting. • Lower scores on individual domains of the 10/66 battery of cognitive tests are associated with higher levels of disability and functional impairment. • It is feasible to administer 10/66 cognitive assessments in participant's own homes in India. • 10/66 cognitive tests are education and culture fair, suitable for use in population based research in India.
    • Combined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells.

      Sheard, Jonathan J.; Southam, Andrew D.; MacKay, Hannah L.; Ellington, Max A; Snow, Martyn D.; Farhat, Khanim L.; Bunce, Christopher M.; Johnson, William E. B.; Aston University, Birmingham; University of Birmingham; University Centre Shrewsbury; Royal Orthopaedic Hospital, Birmingham; University of Chester
      Drug repurposing is a cost effective means of targeting new therapies for cancer. We have examined the effects of the repurposed drugs, bezafibrate, medroxyprogesterone acetate and valproic acid on human osteosarcoma cells, i.e., SAOS2 and MG63 compared with their normal cell counterparts, i.e. mesenchymal stem/stromal cells (MSCs). Cell growth, viability and migration were measured by biochemical assay and live cell imaging, whilst levels of lipid-synthesising enzymes were measured by immunoblotting cell extracts. These drug treatments inhibited the growth and survival of SAOS2 and MG63 cells most effectively when used in combination (termed V-BAP). In contrast, V-BAP treated MSCs remained viable with only moderately reduced cell proliferation. V-BAP treatment also inhibited migratory cell phenotypes. MG63 and SAOS2 cells expressed much greater levels of fatty acid synthase and stearoyl CoA desaturase 1 than MSCs, but these elevated enzyme levels significantly decreased in the V-BAP treated osteosarcoma cells prior to cell death. Hence, we have identified a repurposed drug combination that selectively inhibits the growth and survival of human osteosarcoma cells in association with altered lipid metabolism without adversely affecting their non-transformed cell counterparts.
    • Comment on "PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL human leukemia".

      Perrotti, Danilo; Agarwal, Anupriya; Lucas, Claire; Narla, Goutham; Neviani, Paolo; Odero, Maria D.; Ruvolo, Peter P.; Verrills, Nicole M. (American Association for the Advancement of Science, 2019-07-17)
      LB100 does not sensitize CML stem cells to tyrosine kinase inhibitor–induced apoptosis.
    • Commentary: Endovascular Sealing of Abdominal Aortic Aneurysms: Do Current Data Justify Wider Use?

      Torella, Francesco; McWilliams, Richard G.; Fisher, Robert K. (SAGE Publications, 2018-04-12)
    • Comparing physician associates and foundation year two doctors-in-training undertaking emergency medicine consultations in England: a mixed-methods study of processes and outcomes

      Halter, Mary; orcid: 0000-0001-6636-0621; Drennan, Vari; orcid: 0000-0002-8915-5185; Wang, Chao; Wheeler, Carly; Gage, Heather; Nice, Laura; de Lusignan, Simon; orcid: 0000-0001-5613-6810; Gabe, Jonathan; Brearley, Sally; Ennis, James; et al. (BMJ Publishing Group, 2020-09-01)
      Objectives: To compare the contribution of physician associates to the processes and outcomes of emergency medicine consultations with that of foundation year two doctors-in-training. Design: Mixed-methods study: retrospective chart review using 4 months’ anonymised clinical record data of all patients seen by physician associates or foundation year two doctors-in-training in 2016; review of a subsample of 40 records for clinical adequacy; semi-structured interviews with staff and patients; observations of physician associates. Setting: Three emergency departments in England. Participants: The records of 8816 patients attended by 6 physician associates and 40 foundation year two doctors-in-training; of these n=3197 had the primary outcome recorded (n=1129 physician associates, n=2068 doctor); 14 clinicians and managers and 6 patients or relatives for interview; 5 physician associates for observation. Primary and secondary outcome measures: The primary outcome was unplanned re-attendance at the same emergency department within 7 days. Secondary outcomes: consultation processes, clinical adequacy of care, and staff and patient experience. Results: Re-attendances within 7 days (n=194 (6.1%)) showed no difference between physician associates and foundation year two doctors-in-training (OR 0.87, 95% CI 0.61 to 1.24, p=0.437). If seen by a physician associate, patients were more likely receive an X-ray investigation (OR 2.10, 95% CI 1.72 to 4.24), p<0.001), after adjustment for patient characteristics, triage severity of condition and statistically significant clinician intraclass correlation. Clinical reviewers found almost all patients’ charts clinically adequate. Physician associates were evaluated as assessing patients in a similar way to foundation year two doctors-in-training and providing continuity in the team. Patients were positive about the care they had received from a physician associate, but had poor understanding of the role. Conclusions: Physician associates in emergency departments in England treated patients with a range of conditions safely, and at a similar level to foundation year two doctors-in-training, providing clinical operational efficiencies.
    • Comparison of Mesenchymal Stromal Cells Isolated From Murine Adipose Tissue and Bone Marrow in the Treatment of Spinal Cord Injury

      Takahashi, Ai; Johnson, William Eustace Basil; Uchida, Kenzo; Matsumine, Akihiko; University of Chester, University of Fukui (SAGE, 2018-05-10)
      The use of mesenchymal stromal cell (MSC) transplantation to repair the injured spinal cord has shown consistent benefits in preclinical models. However, the low survival rate of grafted MSC is one of the most important problems. In the injured spinal cord, transplanted cells are exposed to hypoxic conditions and exposed to nutritional deficiency caused by poor vascular supply. Also, the transplanted MSCs face cytotoxic stressors that cause cell death. The aim of this study was to compare adipose-derived MSCs (AD-MSCs) and bone marrow-derived MSCs (BM-MSCs) isolated from individual C57BL6/J mice in relation to: (i) cellular characteristics, (ii) tolerance to hypoxia, oxidative stress and serum-free conditions, and (iii) cellular survival rates after transplantation. AD-MSCs and BM-MSCs exhibited a similar cell surface marker profile, but expressed different levels of growth factors and cytokines. To research their relative stress tolerance, both types of stromal cells were incubated at 20.5% O2 or 1.0% O2 for 7 days. Results showed that AD-MSCs were more proliferative with greater culture viability under these hypoxic conditions than BM-MSCs. The MSCs were also incubated under H2O2-induced oxidative stress and in serum-free culture medium to induce stress. AD-MSCs were better able to tolerate these stress conditions than BMMSCs; similarly when transplanted into the spinal cord injury region in vivo, AD-MSCs demonstrated a higher survival rate post transplantation Furthermore, this increased AD-MSC survival post transplantation was associated with preservation of axons and enhanced vascularization, as delineated by increases in anti-gamma isotype of protein kinase C and CD31 immunoreactivity, compared with the BM-MSC transplanted group. Hence, our results indicate that AD-MSCs are an attractive alternative to BM-MSCs for the treatment of severe spinal cord injury. However, it should be noted that the motor function was equally improved following moderate spinal cord injury in both groups, but with no significant improvement seen unfortunately following severe spinal cord injury in either group
    • Comparison of whole body SOD1 knockout with muscle specific SOD1 knockout mice reveals a role for nerve redox signaling in regulation of degenerative pathways in skeletal muscle.

      Nye, Gareth; Sakellariou, Giorgos; McDonagh, Brian; Porter, Helen; Giakoumaki, Ifigeneia; Earl, Kate; Vasilaki, Aphrodite; Brooks, Susan; Richardson, Arlan; Van Remmen, Holly; et al. (Mary Ann Liebert, 2017-12-12)
      Aims: Lack of Cu,Zn-superoxide dismutase (CuZnSOD) in homozygous knockout mice (Sod1−/−) leads to accelerated age-related muscle loss and weakness, but specific deletion of CuZnSOD in skeletal muscle (mSod1KO mice) or neurons (nSod1KO mice) resulted in only mild muscle functional deficits and failed to recapitulate the loss of mass and function observed in Sod1−/− mice. To dissect any underlying cross-talk between motor neurons and skeletal muscle in the degeneration in Sod1−/− mice, we characterized neuromuscular changes in the Sod1−/− model compared with mSod1KO mice and examined degenerative molecular mechanisms and pathways in peripheral nerve and skeletal muscle. Results: In contrast to mSod1KO mice, myofiber atrophy in Sod1−/− mice was associated with increased muscle oxidative damage, neuromuscular junction degeneration, denervation, nerve demyelination, and upregulation of proteins involved in maintenance of myelin sheaths. Proteomic analyses confirmed increased proteasomal activity and adaptive stress responses in muscle of Sod1−/− mice that were absent in mSod1KO mice. Peripheral nerve from neither Sod1−/− nor mSod1KO mice showed increased oxidative damage or molecular responses to increased oxidation compared with wild type mice. Differential cysteine (Cys) labeling revealed a specific redox shift in the catalytic Cys residue of peroxiredoxin 6 (Cys47) in the peripheral nerve from Sod1−/− mice. Innovation and Conclusion: These findings demonstrate that neuromuscular integrity, redox mechanisms, and pathways are differentially altered in nerve and muscle of Sod1−/− and mSod1KO mice. Results support the concept that impaired redox signaling, rather than oxidative damage, in peripheral nerve plays a key role in muscle loss in Sod1−/− mice and potentially sarcopenia during aging. Antioxid. Redox Signal. 28, 275–295. Innovation This is the first study to compare the molecular mechanisms and pathways that occur in both skeletal muscle and peripheral nerve of Sod1−/− and mSod1KO mice in an effort to examine the relative cross-talk and role of pre- and postsynaptic changes in redox homeostasis in loss of neuromuscular integrity and function that occurs with aging. This study highlights that impaired redox signaling in peripheral nerve rather than oxidative damage appears to play a key role in altering the integrity of peripheral nerves and motor neurons and potentially age-associated muscle atrophy and functional deficits. These results are potentially clinically significant and have widespread implications for the understanding of sarcopenia during aging.
    • Comparisons of attempted suicide between India and UK

      Jones, Steven; Keenan, Paul; Krishna, Murali; University of Chester (Mental Health Nursing Association, 2014)
      This paper aims to raise the issues and dilemmas within India by suicide and attempted suicide. In the UK evidence-based interventions have progressed over the past 20 years and changes are having positive benefits on standards of interventions and reducing deaths in some areas by suicide. However, when comparing one culture’s custom and practice with another, deficits of some areas of practice present and this facilitates some interesting insights for investigation. Fundamentally, the aim is not to place one above another but to aid identification for cross-cultural comparisons leading to practice advancements.
    • Conscientious objection and physician-assisted suicide: a viable option in the UK?

      Willis, Derek; George, Rob (2018-11-15)
      Conscience objection is a proposed way of ensuring that medical practitioners who object to physician-assisted suicide may avoid having to be involved in such a procedure if this is legalised. This right on the part of healthcare professionals already exists in certain circumstances. This paper examines the ethical and legal grounds for conscientious objection for medical professionals and shows how it is heavily criticised in circumstances where it is already used. The paper comes to the conclusion that as the grounds and application of conscience objection are no longer as widely accepted, its future application in any legislation can be called into question. [Abstract copyright: © Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.]
    • Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate

      Hudson, William H.; Pickard, Mark R.; de Vera, Ian M.; Kuiper, Emily G.; Mourtada-Maarabouni, Mirna; Conn, Graeme L.; Kojetin, Douglas J.; Williams, Gwyn T.; Ortlund, Eric A.; Emory University School of Medicine; Keele University; Scripps Research Institute (Nature Publishing Group, 2014-11-07)
      The majority of the eukaryotic genome is transcribed, generating a significant number of long intergenic noncoding RNAs (lincRNAs). Although lincRNAs represent the most poorly understood product of transcription, recent work has shown lincRNAs fulfill important cellular functions. In addition to low sequence conservation, poor understanding of structural mechanisms driving lincRNA biology hinders systematic prediction of their function. Here we report the molecular requirements for the recognition of steroid receptors (SRs) by the lincRNA growth arrest-specific 5 (Gas5), which regulates steroid-mediated transcriptional regulation, growth arrest and apoptosis. We identify the functional Gas5-SR interface and generate point mutations that ablate the SR-Gas5 lincRNA interaction, altering Gas5-driven apoptosis in cancer cell lines. Further, we find that the Gas5 SR-recognition sequence is conserved among haplorhines, with its evolutionary origin as a splice acceptor site. This study demonstrates that lincRNAs can recognize protein targets in a conserved, sequence-specific manner in order to affect critical cell functions.
    • Decision making for refusals of treatment—a framework to consider

      Jones, Steven; Monteith, Paul; Williams, Barry (Journal of Paramedic Practice, 2014-05-02)
      Challenges to practice are encountered on a daily basis by paramedics that often share many common recurring themes around consent or refusal to treatment. The benefits of training and open debate acknowledge the often complex decisions relating to consent and mental capacity and reduce opportunities for future legal challenge. How the law should be integrated into everyday decision making will be examined and a framework proposed to assist practice for defendable decision making. This article was inspired following joint training undertaken with paramedics and local critical incident managers from the police, which highlighted a need for a practical decision-making framework to be available for application during incidents and for use as an analytical tool to aid post-decision reflection and learning at debrief.
    • The developing landscape of diagnostic and prognostic biomarkers for spinal cord injury in cerebrospinal fluid and blood

      Hulme CH; Brown SJ; Fuller HR; Riddell J; Osman A; Chowdhury J; Kumar N; Johnson WE; Wright KT; Keele University, RJAH Orthopaedic Hospital, University of Glasgow, University of Chester (Nature Publishing Group, 2016-12-20)
      STUDY DESIGN: Review study. OBJECTIVES: The identification of prognostic biomarkers of spinal cord injury (SCI) will help to assign SCI patients to the correct treatment and rehabilitation regimes. Further, the detection of biomarkers that predict permanent neurological outcome would aid in appropriate recruitment of patients into clinical trials. The objective of this review is to evaluate the current state-of-play in this developing field. SETTING: Studies from multiple countries were included. METHODS: We have completed a comprehensive review of studies that have investigated prognostic biomarkers in either the blood or cerebrospinal fluid (CSF) of animals and humans following SCI. RESULTS: Targeted and unbiased approaches have identified several prognostic biomarkers in CSF and blood. These proteins associate with cellular damage following SCI and include components from neurons, oligodendrocytes and reactive astrocytes, that is, neurofilament proteins, glial fibrillary acidic protein, Tau and S100 calcium-binding protein β. Unbiased approaches have also identified microRNAs that are specific to SCI, as well as other cell damage-associated proteins. CONCLUSIONS: The discovery and validation of stable, specific, sensitive and reproducible biomarkers of SCI is a rapidly expanding field of research. So far, few studies have utilised unbiased approaches aimed at the discovery of biomarkers within the CSF or blood in this field; however, some targeted approaches have been successfully used. Several studies using various animal models and some with small human patient cohorts have begun to pinpoint biomarkers in the CSF and blood with putative prognostic value. An increased sample size will be required to validate these biomarkers in the heterogeneous clinical setting.
    • The Development and Growth of Tissues Derived From Cranial Neural Crest and Primitive Mesoderm Is Dependent on the Ligation Status of Retinoic Acid Receptor γ: Evidence That Retinoic Acid Receptor γ Functions to Maintain stem/progenitor Cells in the Absence of Retinoic Acid

      Johnson, William Eustace Basil; Wai, Htoo Aung; Aston University (Mary Ann Liebert, Inc, 2015-02-15)
      Retinoic acid (RA) signaling is important to normal development. However, the function of the different RA receptors (RARs)--RARα, RARβ, and RARγ--is as yet unclear. We have used wild-type and transgenic zebrafish to examine the role of RARγ. Treatment of zebrafish embryos with an RARγ-specific agonist reduced somite formation and axial length, which was associated with a loss of hoxb13a expression and less-clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist also disrupted formation of tissues arising from cranial neural crest, including cranial bones and anterior neural ganglia. There was a loss of Sox 9-immunopositive neural crest stem/progenitor cells in the same anterior regions. Pectoral fin outgrowth was blocked by RARγ agonist treatment. However, there was no loss of Tbx-5-immunopositive lateral plate mesodermal stem/progenitor cells and the block was reversed by agonist washout or by cotreatment with an RARγ antagonist. Regeneration of the caudal fin was also blocked by RARγ agonist treatment, which was associated with a loss of canonical Wnt signaling. This regenerative response was restored by agonist washout or cotreatment with the RARγ antagonist. These findings suggest that RARγ plays an essential role in maintaining stem/progenitor cells during embryonic development and tissue regeneration when the receptor is in its nonligated state.
    • Early Transplantation of Mesenchymal Stem Cells After Spinal Cord Injury Relieves Pain Hypersensitivity Through Suppression of Pain-Related Signaling Cascades and Reduced Inflammatory Cell Recruitment

      Johnson, William Eustace Basil; Watanabe, Shuji; Uchida, Kenzo; Nakajima, Hideaki; Matsuo, Hideaki; Sugita, Daisuke; Yoshida, Ai; Honjoh, Kazuya; Baba, Hisatoshi; Aston University, University of Fukui
      Bone marrow-derived mesenchymal stem cells (BMSC) modulate inflammatory/immune responses and promote motor functional recovery after spinal cord injury (SCI). However, the effects of BMSC transplantation on central neuropathic pain and neuronal hyperexcitability after SCI remain elusive. This is of importance because BMSC-based therapies have been proposed for clinical treatment. We investigated the effects of BMSC transplantation on pain hypersensitivity in green fluorescent protein (GFP)-positive bone marrow-chimeric mice subjected to a contusion SCI, and the mechanisms of such effects. BMSC transplantation at day 3 post-SCI improved motor function and relieved SCI-induced hypersensitivities to mechanical and thermal stimulation. The pain improvements were mediated by suppression of protein kinase C-γ and phosphocyclic AMP response element binding protein expression in dorsal horn neurons. BMSC transplants significantly reduced levels of p-p38 mitogen-activated protein kinase and extracellular signal-regulated kinase (p-ERK1/2) in both hematogenous macrophages and resident microglia and significantly reduced the infiltration of CD11b and GFP double-positive hematogenous macrophages without decreasing the CD11b-positive and GFP-negative activated spinal-microglia population. BMSC transplants prevented hematogenous macrophages recruitment by restoration of the blood-spinal cord barrier (BSCB), which was associated with decreased levels of (a) inflammatory cytokines (tumor necrosis factor-α, interleukin-6); (b) mediators of early secondary vascular pathogenesis (matrix metallopeptidase 9); (c) macrophage recruiting factors (CCL2, CCL5, and CXCL10), but increased levels of a microglial stimulating factor (granulocyte-macrophage colony-stimulating factor). These findings support the use of BMSC transplants for SCI treatment. Furthermore, they suggest that BMSC reduce neuropathic pain through a variety of related mechanisms that include neuronal sparing and restoration of the disturbed BSCB, mediated through modulation of the activity of spinal-resident microglia and the activity and recruitment of hematogenous macrophages.
    • The efficacy of using Appropriate Paper-based Technology postural support devices in Kenyan children with Cerebral Palsy

      Barton, Catherine; Buckley, John P.; Samia, Pauline; Williams, Fiona; Taylor, Sue; Lindoewood, Rachel; University Centre Shrewsbury - University of Chester
      Purpose: Appropriate paper-based technology (APT) is used to provide postural support for children with cerebral palsy (CP) in low-resourced settings. This pilot study aimed to evaluate the impact of APT on the children’s and families’ lives. Materials and methods: A convenience sample of children with CP and their families participated. Inclusion was based on the Gross Motor Function Classification System levels IV and V. APT seating or standing frames were provided for six months. A mixed methods impact of APT devices on the children and families included the Family Impact Assistive Technology Scale for Adaptive Seating (FIATS-AS); the Child Engagement in Daily Life (CEDL) questionnaire; and a qualitative assessment from diary/log and semi-structured interviews. Results: Ten children (median 3 years, range 9 months - 7 years). Baseline to follow-up median (IQR) FIATS-AS were: 22.7 (9.3) and 30.3 (10.2), respectively (p = 0.002). Similarly mean (SD) CEDL scores for “frequency” changed from 30.5 (13.2) to 42.08 (5.96) (p=0.021) and children’s enjoyment scores from 2.23 (0.93) to 2.91 (0.79) (p = 0.019). CEDL questionnaire for self-care was not discriminatory; seven families scored zero at both baseline and 6 months. Qualitative interviews revealed three key findings; that APT improved functional ability, involvement/interaction in daily-life situations, and a reduced family burden of care. Conclusion: APT devices used in Kenyan children with non-ambulant CP had a meaningful positive effect on both the children’s and their families’ lives.
    • Electro Convulsive Therapy: Milestones in its history

      Jones, Colin; Jones, Steven; University of Chester (Mental Health Nurses Association, 2018)
      ECT is a treatment where an electrical current is passed briefly through electrodes applied to the scalp to induce generalised seizure activity. This article explores the origins and developmental milestones of ECT, examines the literature on the history of ECT and concludes with the author’s work experiences.
    • Embedding recovery based approaches into mental health nurse training- a reflective account

      Jones, Steven; Bifarin, Oladayo O.; University of Chester (Mark Allen Healthcare, 2018-11-02)
      Background: Mental health nursing has undoubtedly progressed as a profession but is at a hiatus that is not assisted by government policy and decreased resources. Aims: This reflective account explores some of the considerable expectations placed upon qualified nurses and the real tensions that influence care delivery standards. Methods: Reflecting on experiences gained in clinical settings, underpinned by literature on recovery, some of the expectations placed on qualified nurses in contemporary mental health service delivery are examined. Conclusion: In order to adequately inform the practices and skill set of contemporary mental health nurses, recovery models and clinical staff input should play a central role in nurse education. Education and clinical practice areas should continue to move towards each other and seize every initiative to ensure both are on the same page.
    • Endocytotic potential governs magnetic particle loading in dividing neural cells: studying modes of particle inheritance

      Tickle, Jacqueline A.; Jenkins, Stuart I.; Polyak, Boris; Pickard, Mark R.; Chari, Divya M.; Keele University, United Kingdom; Drexel University College of Medicine, Philadelphia, USA (Future Medicine, 2016-01-10)
      AIM: To achieve high and sustained magnetic particle loading in a proliferative and endocytotically active neural transplant population (astrocytes) through tailored magnetite content in polymeric iron oxide particles. MATERIALS & METHODS: MPs of varying magnetite content were applied to primary-derived rat cortical astrocytes ± static/oscillating magnetic fields to assess labeling efficiency and safety. RESULTS: Higher magnetite content particles display high but safe accumulation in astrocytes, with longer-term label retention versus lower/no magnetite content particles. Magnetic fields enhanced loading extent. Dynamic live cell imaging of dividing labeled astrocytes demonstrated that particle distribution into daughter cells is predominantly 'asymmetric'. CONCLUSION: These findings could inform protocols to achieve efficient MP loading into neural transplant cells, with significant implications for post-transplantation tracking/localization.
    • Eukarion-134 Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Dysfunction in Human Skeletal Muscle Cells

      Nye, Gareth; Thoma, Anastasia; Lyon, Max; Al-Shanti, Nasser; Cooper, Robert; Lightfoot, Adam; University of Chester; Manchester Metropolitan University; University of Liverpool
      Maladaptive endoplasmic reticulum (ER) stress is associated with modified reactive oxygen species (ROS) generation and mitochondrial abnormalities; and is postulated as a potential mechanism involved in muscle weakness in myositis, an acquired autoimmune neuromuscular disease. This study investigates the impact of ROS generation in an in vitro model of ER stress in skeletal muscle, using the ER stress inducer tunicamycin (24 h) in the presence or absence of a superoxide dismutase/catalase mimetic Eukarion (EUK)-134. Tunicamycin induced maladaptive ER stress, which was mitigated by EUK-134 at the transcriptional level. ER stress promoted mitochondrial dysfunction, described by substantial loss of mitochondrial membrane potential, as well as a reduction in respiratory control ratio, reserve capacity, phosphorylating respiration, and coupling efficiency, which was ameliorated by EUK-134. Tunicamycin induced ROS-mediated biogenesis and fusion of mitochondria, which, however, had high propensity of fragmentation, accompanied by upregulated mRNA levels of fission-related markers. Increased cellular ROS generation was observed under ER stress that was prevented by EUK-134, even though no changes in mitochondrial superoxide were noticeable. These findings suggest that targeting ROS generation using EUK-134 can amend aspects of ER stress-induced changes in mitochondrial dynamics and function, and therefore, in instances of chronic ER stress, such as in myositis, quenching ROS generation may be a promising therapy for muscle weakness and dysfunction.
    • The experience of stigma in inflammatory bowel disease: an interpretive (hermeneutic) phenomenological study

      Dibley, Lesley; Norton, Christine; Whitehead, Elizabeth; University of Chester (John Wiley & Sons Ltd, 2017-11-03)
      Aim to explore experiences of stigma in people with inflammatory bowel disease. Background Diarrhoea, urgency and incontinence are common symptoms in inflammatory bowel disease. Social rules stipulate full control of bodily functions in adulthood: poor control may lead to stigmatisation, affecting patients’ adjustment to disease. Disease-related stigma is associated with poorer clinical outcomes but qualitative evidence is minimal. Design An interpretive (hermeneutic) phenomenological study of the lived experience of stigma in inflammatory bowel disease. Methods Forty community-dwelling adults with a self-reported diagnosis of inflammatory bowel disease were recruited purposively. Participants reported feeling stigmatised or not and experiencing faecal incontinence or not. Unstructured interviews took place in participants’ homes in the United Kingdom (September 2012 – May 2013). Data were analysed using Diekelmann's interpretive method. Findings Three constitutive patterns - Being in and out of control, Relationships and social Support and Mastery and mediation - reveal the experience of disease-related stigma, occurring regardless of continence status and because of name and type of disease. Stigma recedes when mastery over disease is achieved through development of resilience - influenced by humour, perspective, mental wellbeing and upbringing (childhood socialisation about bodily functions). People travel in and out of stigma, dependent on social relationships with others including clinicians and tend to feel less stigmatised over time. Conclusion Emotional control, social support and mastery over disease are key to stigma reduction. By identifying less resilient patients, clinicians can offer appropriate support, accelerating the patient's path towards disease acceptance and stigma reduction.