• Targeting long non-coding RNAs (lncRNAs) with oligonucleotides in cancer therapy

      Pickard, Mark R.; Williams, Gwyn T.; University of Chester; Keele University (AME Publishing Company, 2016-10)
      No abstract
    • The Comparative Effects of Mesenchymal Stem Cell Transplantation Therapy for Spinal Cord Injury in Humans and Animal Models: A Systematic Review and Meta-Analysis

      Johnson, Louis D. V.; email: louisdvj@gmail.com; Pickard, Mark R.; email: m.pickard@chester.ac.uk; Johnson, William E. B.; email: eustace.johnson@chester.ac.uk (MDPI, 2021-03-16)
      Animal models have been used in preclinical research to examine potential new treatments for spinal cord injury (SCI), including mesenchymal stem cell (MSC) transplantation. MSC transplants have been studied in early human trials. Whether the animal models represent the human studies is unclear. This systematic review and meta-analysis has examined the effects of MSC transplants in human and animal studies. Following searches of PubMed, Clinical Trials and the Cochrane Library, published papers were screened, and data were extracted and analysed. MSC transplantation was associated with significantly improved motor and sensory function in humans, and significantly increased locomotor function in animals. However, there are discrepancies between the studies of human participants and animal models, including timing of MSC transplant post-injury and source of MSCs. Additionally, difficulty in the comparison of functional outcome measures across species limits the predictive nature of the animal research. These findings have been summarised, and recommendations for further research are discussed to better enable the translation of animal models to MSC-based human clinical therapy.
    • The Differences in Acute Management of Asthma in Adults and Children

      Chavasse, Richard; Scott, Stephen (Frontiers Media S.A., 2019-03-11)
      Acute asthma or wheeze is a common presentation to emergency services for both adults and children. Although there are phenotypic differences between asthma syndromes, the management of acute symptoms follow similar lines. This article looks at the similarities and differences in approaches for children and adults. Some of these may be age dependent, such as the physiological parameters used to define the severity of the attack or the use of age appropriate inhaler devices. Other differences may reflect the availability of evidence. In other areas there is conflicting evidence between adult and pediatric studies such as a temporary increase in dose of inhaled corticosteroids during an acute attack. Overall there are more similarities than differences.
    • Training nurses in Mental Health Assessment using GMHAT/PC in India

      Jones, Steven; Keenan, Paul; Danivas, Vijay; Krishna, Murali; Rajendra, Rajgopal; University of Chester (Indian Psychiatric Society, 2017-07-23)
      Book chapter; Training of Indian general nurses in a hospital setting required the structure offered by the Global Mental Health Assessment Tool (GMHAT) that would provide a framework to underpin mental health assessment training. Attitudes of those undertaking the training and current levels of knowledge and awareness to mental health issues was explored prior to any training occurring in the use of GMHAT, that we considered fundamental to good mental health practice
    • Treatment-Free Remission in Chronic Myeloid Leukemia: Can We Identify Prognostic Factors?

      Lucas, Claire; Saifullah, Hilbeen H.; University of Chester; University of Liverpool (MDPI, 2021-08-19)
      Following the development of tyrosine kinase inhibitors (TKI), the survival of patients with chronic myeloid leukaemia (CML) drastically improved. With the introduction of these agents, CML is now considered a chronic disease for some patients. Taking into consideration the side effects, toxicity, and high cost, discontinuing TKI became a goal for patients with chronic phase CML. Patients who achieved deep molecular response (DMR) and discontinued TKI, remained in treatment-free remission (TFR). Currently, the data from the published literature demonstrate that 40–60% of patients achieve TFR, with relapses occurring within the first six months. In addition, almost all patients who relapsed regained a molecular response upon retreatment, indicating TKI discontinuation is safe. However, there is still a gap in understanding the mechanisms behind TFR, and whether there are prognostic factors that can predict the best candidates who qualify for TKI discontinuation with a view to keeping them in TFR. Furthermore, the information about a second TFR attempt and the role of gradual de-escalation of TKI before complete cessation is limited. This review highlights the factors predicting success or failure of TFR. In addition, it examines the feasibility of a second TFR attempt after the failure of the first one, and the current guidelines concerning TFR in clinical practice.
    • Tuberculosis notification in a private tertiary care teaching hospital in South India: a mixed-methods study

      Siddaiah, Archana; Ahmed, Mohammad Naseer; Kumar, Ajay M. V.; D’Souza, George; Wilkinson, Ewan; Maung, Thae Maung; Rodrigues, Rashmi (BMJ Publishing Group, 2019-02-05)
      Objectives India contributes approximately 25% of the ‘missing’ cases of tuberculosis (TB) globally. Even though ~50% of patients with TB are diagnosed and treated within India’s private sector, few are notified to the public healthcare system. India’s TB notification policy mandates that all patients with TB are notified through Nikshay (TB notification portal). We undertook this study in a private hospital to assess the proportion notified and factors affecting TB notifications. We explored barriers and probable solutions to TB notification qualitatively from health provider’s perspective. Study setting Private, tertiary care, teaching hospital in Bengaluru, South India. Methodology This was a mixed-methods study. Quantitative component comprised a retrospective review of hospital records between 1 January 2015 and 31 December 2017 to determine TB notifications. The qualitative component comprised key informant interviews and focus groups to elicit the barriers and facilitators of TB notification. Results Of 3820 patients diagnosed and treated, 885 (23.2%) were notified. Notifications of sputum smear-positive patients were significantly more likely, while notifications of children were less likely. Qualitative analysis yielded themes reflecting the barriers to TB notification and their solutions. Themes related to barriers were: (1) basic diagnostic procedures and treatment promote notification; (2) misconceptions regarding notification and its process are common among healthcare providers; (3) despite a national notification system other factors have prevented notification of all patients; and (4) establishing hospital systems for notification will go a long way in improving notifications. Conclusions The proportion of patients with TB notified by the hospital was low. A comprehensive approach both by the hospital management and the national TB programme is necessary for improving notification. This includes improving awareness among healthcare providers about the requirement for TB notifications, establishing a single notification portal in hospital, digitally linking hospital records to Nikshay and designating one person to be responsible for notification.
    • Two independent proteomic approaches provide a comprehensive analysis of the synovial fluid proteome response to Autologous Chondrocyte Implantation

      Hulme, Charlotte H.; Wilson, Emma L.; Fuller, Heidi R.; Roberts, Sally; Richardson, James B.; Gallacher, Pete; Peffers, Mandy J.; Shirran, Sally L.; Botting, Catherine H.; Wright, Karina T.; et al. (BioMed Central, 2018-05-02)
      Background: Autologous chondrocyte implantation (ACI) has a failure rate of approximately 20%, but it is yet to be fully understood why. Biomarkers are needed that can pre-operatively predict in which patients it is likely to fail, so that alternative or individualised therapies can be offered. We previously used label-free quantitation (LF) with a dynamic range compression proteomic approach to assess the synovial fluid (SF) of ACI responders and non-responders. However, we were able to identify only a few differentially abundant proteins at baseline. In the present study, we built upon these previous findings by assessing higher-abundance proteins within this SF, providing a more global proteomic analysis on the basis of which more of the biology underlying ACI success or failure can be understood. Methods: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomic analysis was used to assess SF from ACI responders (mean Lysholm improvement of 33; n = 14) and non-responders (mean Lysholm decrease of 14; n = 13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins in iTRAQ and combined iTRAQ and LF datasets were investigated using pathway and network analyses. Results: iTRAQ proteomic analysis confirmed our previous finding that there is a marked proteomic shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥ 2.0-fold change and p < 0.05 between stages I and II in responders and non-responders, respectively). Further, it highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, which were not found in the LF study, 16 of which were altered at baseline. The differential expression of two proteins (complement C1s subcomponent and matrix metalloproteinase 3) was confirmed biochemically. Combination of the iTRAQ and LF proteomic datasets generated in-depth SF proteome information that was used to generate interactome networks representing ACI success or failure. Functional pathways that are dysregulated in ACI non-responders were identified, including acute-phase response signalling. Conclusions: Several candidate biomarkers for baseline prediction of ACI outcome were identified. A holistic overview of the SF proteome in responders and non-responders to ACI  has been profiled, providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.
    • Uncertainty, Anxiety and Isolation: Experiencing the COVID-19 Pandemic and Lockdown as a Woman with Polycystic Ovary Syndrome (PCOS)

      Atkinson, Lou; Kite, Chris; McGregor, G; James, Tamsin; Clark, Cain C T; Randeva, Harpal S; Kyrou, Ioannis; Aston University; University of Chester; Coventry University; University Hospitals Coventry and Warwickshire; University of Warwick
      Background: The COVID-19 pandemic and the related lockdown measures presented a significant risk to physical and mental wellbeing in affected populations. Women with polycystic ovary syndrome (PCOS) are predisposed to several cardio-metabolic risk factors which increase the susceptibility to severe COVID-19 and also exhibit increased likelihood of impaired mental health wellbeing. Therefore, these women who usually receive care from multiple primary and specialist healthcare services may be disproportionately impacted by this pandemic and the related restrictions. This study aimed to explore the lived experience of the first UK national lockdown as a woman with PCOS. Methods: As part of a larger cross-sectional study, 12 women with PCOS living in the UK during the first national COVID-19 lockdown were recruited to a qualitative study. Telephone interviews were conducted in June/July of 2020, and data collected were subjected to thematic analysis. Results: Five themes were identified. “My PCOS Journey” describes participants’ experiences of diagnosis, treatment and ongoing management of their PCOS. “Living Through Lockdown” describes the overall experience and impact of the lockdown on all aspects of participants’ lives. “Self-care and Managing Symptoms” describe multiple challenges to living well with PCOS during the lockdown, including lack of access to supplies and services, and disruption to weight management. “Healthcare on Hold” describes the uncertainty and anxiety associated with delays in accessing specialised healthcare for a range of PCOS aspects, including fertility treatment. “Exacerbating Existing Issues” captures the worsening of pre-existing mental health issues, and an increase in health anxiety and feelings of isolation. Conclusion: For the women with PCOS in this study, the COVID-19 pandemic and the first national lockdown was mostly experienced as adding to the pre-existing challenges of living with their condition. The mental health impact experienced by the study participants was increased due to lack of access to their normal support strategies, limitations on healthcare services and uncertainty about their risk of COVID-19.
    • Use of GMHAT/PC in old age population in India

      Krishna, Murali; Ramya, M.; Sharma, Vimal; Jones, Steven; University of Chester (Indian Psychiatric society, 2017)
      Book chapter
    • Using magnetic nanoparticles for gene transfer to neural stem cells: stem cell propagation method influences outcomes

      Pickard, Mark R.; Adams, Christopher F.; Barraud, Perrine; Chari, Divya M.; Keele University, United Kingdom; University of Cambridge, United Kingdom (Multidisciplinary Digital Publishing Institute, 2015-04-24)
      Genetically engineered neural stem cell (NSC) transplants offer a key strategy to augment neural repair by releasing therapeutic biomolecules into injury sites. Genetic modification of NSCs is heavily reliant on viral vectors but cytotoxic effects have prompted development of non-viral alternatives, such as magnetic nanoparticle (MNPs). NSCs are propagated in laboratories as either 3-D suspension "neurospheres" or 2-D adherent "monolayers". MNPs deployed with oscillating magnetic fields ("magnetofection technology") mediate effective gene transfer to neurospheres but the efficacy of this approach for monolayers is unknown. It is important to address this issue as oscillating magnetic fields dramatically enhance MNP-based transfection in transplant cells (e.g., astrocytes and oligodendrocyte precursors) propagated as monolayers. We report for the first time that oscillating magnetic fields enhanced MNP-based transfection with reporter and functional (basic fibroblast growth factor; FGF2) genes in monolayer cultures yielding high transfection versus neurospheres. Transfected NSCs showed high viability and could re-form neurospheres, which is important as neurospheres yield higher post-transplantation viability versus monolayer cells. Our results demonstrate that the combination of oscillating magnetic fields and a monolayer format yields the highest efficacy for MNP-mediated gene transfer to NSCs, offering a viable non-viral alternative for genetic modification of this important neural cell transplant population.
    • What is the effect of aerobic exercise intensity on cardiorespiratory fitness in those undergoing cardiac rehabilitation? A systematic review with meta-analysis

      Mitchell, Braden L.; Lock, Merilyn J.; Parfitt, Gaynor; Buckley, John P.; Davison, Kade; Eston, Roger; University of South Australia, University Centre Shrewsbury/University of Chester (BMJ, 2018-08-18)
      18 Objective: Assess the role of exercise intensity on changes in cardiorespiratory fitness (CRF) in 19 patients with cardiac conditions attending exercise-based cardiac rehabilitation. 20 Design: Systematic review with meta-analysis. 21 Data sources: MEDLINE, Embase, CINAHL, SPORTDiscus, PsycINFO and Web of Science. 22 Eligibility criteria for selection: Studies assessing change in CRF (reported as peak oxygen uptake; 23 V̇O2peak) in patients post-myocardial infarction and revascularisation, following exercise-based 24 cardiac rehabilitation. Studies establishing V̇O2peak via symptom-limited exercise test with ventilatory 25 gas analysis and reported intensity of exercise during rehabilitation were included. Studies with 26 mean ejection fraction <40% were excluded. 27 Results: 128 studies including 13,220 patients were included. Interventions were classified as 28 moderate, moderate-to-vigorous or vigorous intensity based on published recommendations. 29 Moderate and moderate-to-vigorous intensity interventions were associated with a moderate 30 increase in relative V̇O2peak (standardised mean difference ± 95% CI = 0.94 ± 0.30 and 0.93 ± 0.17, 31 respectively), and vigorous-intensity exercise with a large increase (1.10 ± 0.25). Moderate and 32 vigorous intensity interventions were associated with moderate improvements in absolute V̇O2peak 33 (0.63 ± 0.34 and 0.93 ± 0.20, respectively), whereas moderate-to-vigorous intensity interventions 34 elicited a large effect (1.27 ± 0.75). Large heterogeneity among studies was observed for all analyses. 35 Subgroup analyses yielded statistically significant, but inconsistent, improvements in CRF. 36 Conclusion: Engagement in exercise-based cardiac rehabilitation was associated with significant 37 improvements in both absolute and relative V̇O2peak. Although exercise of vigorous intensity 38 produced the greatest pooled effect for change in relative V̇O2peak, differences in pooled effects 39 between intensities could not be considered clinically meaningful.
    • Will Plan S put learned societies in jeopardy?

      Purton, Mary; Michelangeli, Francesco; Fésüs, László (Wiley, 2019-02-25)