• Quantifying the impact of tissue metabolism on solute transport in feto-placental microvascular networks

      Nye, Gareth; Erlich, Alexander; Brownbill, Paul; Chernyavsky, Igor; Jenson, Oliver; University of Manchester (Royal Society, 2019-08-16)
      The primary exchange units in the human placenta are terminal villi, in which fetal capillary networks are surrounded by a thin layer of villous tissue, separating fetal from maternal blood. To understand how the complex spatial structure of villi influences their function, we use an image-based theoretical model to study the effect of tissue metabolism on the transport of solutes from maternal blood into the fetal circulation. For solute that is taken up under first-order kinetics, we show that the transition between flow-limited and diffusion-limited transport depends on two new dimensionless parameters defined in terms of key geometric quantities, with strong solute uptake promoting flow-limited transport conditions. We present a simple algebraic approximation for solute uptake rate as a function of flow conditions, metabolic rate and villous geometry. For oxygen, accounting for nonlinear kinetics using physiological parameter values, our model predicts that villous metabolism does not significantly impact oxygen transfer to fetal blood, although the partitioning of fluxes between the villous tissue and the capillary network depends strongly on the flow regime
    • Reciprocal regulation of GAS5 lncRNA levels and mTOR inhibitor action in prostate cancer cells.

      Yacqub-Usman, Kiren; Pickard, Mark R.; Williams, Gwyn T.; Keele University (Wiley, 2015-02-03)
      BACKGROUND: New therapies are required for castrate-resistant prostate cancer (CRPC), and growth-arrest specific 5 (GAS5) lncRNA, which riborepresses androgen receptor action, may offer novel opportunities in this regard. This lncRNA promotes the apoptosis of prostate cancer cells and its levels decline as prostate cancer cells acquire castrate-resistance, so that enhancing GAS5 expression may improve the effectiveness of chemotherapies. Since GAS5 is a member of the 5' terminal oligopyrimidine gene family, we have examined mTOR inhibition as a strategy to increase GAS5 expression. Furthermore, we have determined if GAS5 itself mediates the action of mTOR inhibitors, as demonstrated for other chemotherapeutic agents in prostate cancer cells. METHODS: The effects of mTOR inhibitors on GAS5 lncRNA levels and cell growth were determined in a range of prostate cancer cell lines. Transfection of cells with GAS5 siRNAs and plasmid constructs was performed to determine the involvement of GAS5 lncRNA in mTOR inhibitor action. RESULTS: First generation mTORC1, combined mTORC1/mTORC2 and dual PI3K/mTOR inhibitors all increased cellular GAS5 levels and inhibited culture growth in androgen-dependent (LNCaP) and androgen-sensitive (22Rv1) cell lines, but not in androgen-independent (PC-3 and DU 145) cell lines. The latter exhibited low endogenous GAS5 expression, and GAS5 silencing in LNCaP and 22Rv1 cells decreased the sensitivity to mTOR inhibitors, whereas transfection of GAS5 lncRNA sensitized PC-3 and DU 145 cells to these agents. CONCLUSION: mTOR inhibition enhances GAS5 transcript levels in certain prostate cancer cell lines. This selectivity is likely to be related to endogenous GAS5 expression levels, since GAS5 lncRNA is itself required for mTOR inhibitor action in prostate cancer cells.
    • Recombinant Plasmodium vivax circumsporozoite surface protein allelic variants: antibody recognition by individuals from three communities in the Brazilian Amazon

      Ferreira Soares, Isabela; López-Camacho, César; Nunes Rodrigues-da-Silva, Rodrigo; da Silva Matos, Ada; de Oliveira Baptista, Barbara; Renato Rivas Totino, Paulo; Medeiros de Souza, Rodrigo; Harrison, Kate; Gimenez, Alba Marina; Oliveira de Freitas, Elisângela; et al.
      Circumsporozoite protein (CSP) variants of P. vivax, besides having variations in the protein repetitive portion, can differ from each other in aspects such as geographical distribution, intensity of transmission, vectorial competence and immune response. Such aspects must be considered to P. vivax vaccine development. Therefore, we evaluated the immunogenicity of novel recombinant proteins corresponding to each of the three P. vivax allelic variants (VK210, VK247 and P. vivax-like) and of the C-terminal region (shared by all PvCSP variants) in naturally malaria-exposed populations of Brazilian Amazon. Our results demonstrated that PvCSP-VK210 was the major target of humoral immune response in studied population, presenting higher frequency and magnitude of IgG response. The IgG subclass profile showed a prevalence of cytophilic antibodies (IgG1 and IgG3), that seem to have an essential role in protective immune response. Differently of PvCSP allelic variants, antibodies elicited against C-terminal region of protein did not correlate with epidemiological parameters, bringing additional evidence that humoral response against this protein region is not essential to protective immunity. Taken together, these findings increase the knowledge on serological response to distinct PvCSP allelic variants and may contribute to the development of a global and effective P. vivax vaccine.
    • Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy.

      Pickard, Mark R.; Williams, Gwyn T.; Keele University, United Kingdom (2014-05-01)
      The putative tumour suppressor and apoptosis-promoting gene, growth arrest-specific 5 (GAS5), encodes long ncRNA (lncRNA) and snoRNAs. Its expression is down-regulated in breast cancer, which adversely impacts patient prognosis. In this preclinical study, the consequences of decreased GAS5 expression for breast cancer cell survival following treatment with chemotherapeutic agents are addressed. In addition, functional responses of triple-negative breast cancer cells to GAS5 lncRNA are examined, and mTOR inhibition as a strategy to enhance cellular GAS5 levels is investigated. Breast cancer cell lines were transfected with either siRNA to GAS5 or with a plasmid encoding GAS5 lncRNA and the effects on breast cancer cell survival were determined. Cellular responses to mTOR inhibitors were evaluated by assaying culture growth and GAS5 transcript levels. GAS5 silencing attenuated cell responses to apoptotic stimuli, including classical chemotherapeutic agents; the extent of cell death was directly proportional to cellular GAS5 levels. Imatinib action in contrast, was independent of GAS5. GAS5 lncRNA promoted the apoptosis of triple-negative and oestrogen receptor-positive cells but only dual PI3K/mTOR inhibition was able to enhance GAS5 levels in all cell types. Reduced GAS5 expression attenuates apoptosis induction by classical chemotherapeutic agents in breast cancer cells, providing an explanation for the relationship between GAS5 expression and breast cancer patient prognosis. Clinically, this relationship may be circumvented by the use of GAS5-independent drugs such as imatinib, or by restoration of GAS5 expression. The latter may be achieved by the use of a dual PI3K/mTOR inhibitor, to improve apoptotic responses to conventional chemotherapies.
    • Regulation of the cell cycle and cell death by protein phosphatase 4 in breast cancer cell lines

      Mohammed, Hiba N.; Pickard, Mark R.; Williams, Gwyn T.; Mourtada-Maarabouni, Mirna; Keele University, United Kingdom (NCRI Cancer Conference 2014 Abstracts, 2014)
      Background At the molecular level, cell death is often regulated by the level of phosphorylation of particular proteins, i.e. by the balance of between opposing kinase and phosphatase activities on those proteins. Protein phosphatase 4 (PP4) is a PP2A-related serine/threonine phosphatase. PP2A has already been implicated in the control of cell proliferation, cell cycle and tumorigenesis. Using a functional expression cloning strategy, we have previously identified the catalytic subunit of PP4 (PP4c) as an important gene influencing the regulation of both apoptosis and cell proliferation in human leukaemic cell lines and in normal lymphocytes. The aims of this study were to examine the effects of PP4c overexpression and silencing on the cell death and survival of breast cancer cell lines. Method MCF7 and MDA-MB-231 cells were transfected with pcDNA3.1 encoding PP4c (pcDNA3-PP4c) or siRNAs to different PP4c sequences. Cells transfected with scrambled siRNA or empty vector were considered as controls. Culture viability, apoptosis and cell cycle were assessed post transfection. Results In MCF7 and metastatic MDA-MB-231 cells, PP4c over-expression exerted an inhibitory effect on cell proliferation, enhanced spontaneous apoptosis and decreased their colony forming ability. Conversely, siRNA mediated silencing of PP4 enhanced the proliferation and survival of MCF7 and MDA-MB-231 cells, affected cell cycle kinetics by enhancing the proportion of cells in S and G2/M phases, increased the colony forming ability and stimulated the anchorage independent growth. Conclusion PP4c promotes cell death and inhibits proliferation in breast cells, suggestive of a role of PP4c as tumour suppressor gene. Down regulation of PP4c expression increases cell survival, proliferation and anchorage independent growth of breast cancer cells, indicating a potential link between the PP4c expression levels, tumorigenesis and metastasis.
    • The ReSiT study (reducing sitting time): rationale and protocol for an exploratory pilot study of an intervention to reduce sitting time among office workers

      Gardner, Benjamin; Dewitt, Stephen; Smith, Lee; Biddle, Stuart J. H.; Mansfield, Louise; Buckley, John P.; University Centre Shrewsbury (BMC, 2017-11-28)
      Background: Desk-based workers engage in long periods of uninterrupted sitting time, which has been associated with morbidity and premature mortality. Previous workplace intervention trials have demonstrated the potential of providing sit-stand workstations, and of administering motivational behaviour change techniques, for reducing sitting time. Yet, few studies have combined these approaches or explored the acceptability of discrete sitting-reduction behaviour change strategies. This paper describes the rationale for a sitting-reduction intervention that combines sit-stand workstations with motivational techniques, and procedures for a pilot study to explore the acceptability of core intervention components among university office workers. Methods: The intervention is based on a theory and evidence-based analysis of why office workers sit, and how best to reduce sitting time. It seeks to enhance motivation and capability, as well as identify opportunities, required to reduce sitting time. Thirty office workers will participate in the pilot study. They will complete an initial awareness-raising monitoring and feedback task and subsequently receive a sit-stand workstation for a 12-week period. They will also select from a ‘menu’ of behaviour change techniques tailored to self-declared barriers to sitting reduction, effectively co-producing and personally tailoring their intervention. Interviews at 1, 6, and 12 weeks post-intervention will explore intervention acceptability. Discussion: To our knowledge, this will be the first study to explore direct feedback from office workers on the acceptability of discrete tailored sitting-reduction intervention components that they have received. Participants’ choice of and reflections on intervention techniques will aid identification of strategies suitable for inclusion in the next iteration of the intervention, which will be delivered in a self-administered format to minimise resource burden.
    • Retroviral insertional mutagenesis implicates E3 ubiquitin ligase RNF168 in the control of cell proliferation and survival

      Kizilors, Aytug; Pickard, Mark R.; Schulte, Cathleen E.; Yacqub-Usman, Kiren; McCarthy, Nicola J.; Gan, Shu-Uin; Darling, David; Gäken, Joop; Williams, Gwyn T.; Farzaneh, Farzin; et al. (Portland Press, 2017-08-14)
      The E3 ubiquitin ligase RNF168 is a ring finger protein that has previously been identified to play an important regulatory role in the repair of double-strand DNA breaks. In the present study, an unbiased forward genetics functional screen in mouse granulocyte/ macrophage progenitor cell line FDCP1 has identified E3 ubiquitin ligase RNF168 as a key regulator of cell survival and proliferation. Our data indicate that RNF168 is an important component of the mechanisms controlling cell fate, not only in human and mouse haematopoietic growth factor-dependent cells, but also in the human breast epithelial cell line MCF-7. These observations therefore suggest that RNF168 provides a connection to key pathways controlling cell fate, potentially through interaction with PML nuclear bodies and/or epigenetic control of gene expression. Our study is the first to demonstrate a critical role for RNF168 in the in the mechanisms regulating cell proliferation and survival, in addition to its well-established role in DNA repair.
    • Second generation tyrosine kinase inhibitors prevent disease progression in high-risk (high CIP2A) chronic myeloid leukaemia patients.

      Lucas, Claire; Harris, Robert; Holcroft, Alison; Scott, Laura; Carmell, Natasha; McDonald, Elizabeth; Polydoros, Fotis; Clark, Richard (Nature, 2015-03-13)
      High cancerous inhibitor of PP2A (CIP2A) protein levels at diagnosis of chronic myeloid leukaemia (CML) are predictive of disease progression in imatinib-treated patients. It is not known whether this is true in patients treated with second generation tyrosine kinase inhibitors (2G TKI) from diagnosis, and whether 2G TKIs modulate the CIP2A pathway. Here, we show that patients with high diagnostic CIP2A levels who receive a 2G TKI do not progress, unlike those treated with imatinib (P=<0.0001). 2G TKIs induce more potent suppression of CIP2A and c-Myc than imatinib. The transcription factor E2F1 is elevated in high CIP2A patients and following 1 month of in vivo treatment 2G TKIs suppress E2F1 and reduce CIP2A; these effects are not seen with imatinib. Silencing of CIP2A, c-Myc or E2F1 in K562 cells or CML CD34+ cells reactivates PP2A leading to BCR-ABL suppression. CIP2A increases proliferation and this is only reduced by 2G TKIs. Patients with high CIP2A levels should be offered 2G TKI treatment in preference to imatinib. 2G TKIs disrupt the CIP2A/c-Myc/E2F1 positive feedback loop, leading to lower disease progression risk. The data supports the view that CIP2A inhibits PP2Ac, stabilising E2F1, creating a CIP2A/c-Myc/E2F1 positive feedback loop, which imatinib cannot overcome.
    • The sedentary office: an expert statement on the growing case for change towards better health and productivity

      Buckley, John P.; Hedge, Alan; Yates, Thomas; Copeland, Robert J.; Loosemore, Michael; Hamer, Mark; Bradley, Gavin; Dunstan, David W.; University Centre Shrewsbury (BMJ, 2015-06-01)
      An international group of experts convened to provide guidance for employers to promote the avoidance of prolonged periods of sedentary work. The set of recommendations was developed from the totality of the current evidence, including long-term epidemiological studies and interventional studies of getting workers to stand and/or move more frequently. The evidence was ranked in quality using the four levels of the American College of Sports Medicine. The derived guidance is as follows: for those occupations which are predominantly desk based, workers should aim to initially progress towards accumulating 2 h/day of standing and light activity (light walking) during working hours, eventually progressing to a total accumulation of 4 h/day (prorated to part-time hours). To achieve this, seated-based work should be regularly broken up with standing-based work, the use of sit–stand desks, or the taking of short active standing breaks. Along with other health promotion goals (improved nutrition, reducing alcohol, smoking and stress), companies should also promote among their staff that prolonged sitting, aggregated from work and in leisure time, may significantly and independently increase the risk of cardiometabolic diseases and premature mortality. It is appreciated that these recommendations should be interpreted in relation to the evidence from which they were derived, largely observational and retrospective studies, or short-term interventional studies showing acute cardiometabolic changes. While longer term intervention studies are required, the level of consistent evidence accumulated to date, and the public health context of rising chronic diseases, suggest initial guidelines are justified. We hope these guidelines stimulate future research, and that greater precision will be possible within future iterations.
    • Social and Clinical Correlates of Stimulant Use Disorder (Mephedrone) in a Tertiary Mental Health Setting in Mumbai: A Pilot Exploratory Study

      Rao, S. Poornima; Kale, Vinayak Pandurang; Panigrahi, Sunilkumar; Krishna, Murali; Jones, Steven; Majgi, Sumanth Mallikarjuna; Bharath, D. U.; University of Chester
      Introduction: Increasing mephedrone use is a major public health concern in India. There are limited data on sociodemographic determinants and psychiatric comorbidity associated with stimulant use disorder (mephedrone) (SUD‑M) from India. Aim: The primary objective of this study was to report the clinical and social correlates of SUD‑M among those presenting to specialist mental health services in Mumbai, India. Methods: Patients with SUD-M were recruited from a clinical setting. Standardized culturally validated assessments were carried out to obtain information about sociodemographics and mental health: comorbid psychopathology Brief Psychiatric Rating Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and Minnesota Multiphasic Personality Inventory‑2 for personality traits and a clinical assessment for diagnoses of mental disorders. Results: Seventy patients (aged between 21 and 30 years, of whom 58 men) with SUD-M consented. SUD‑M was more common among young men from the low socioeconomic position. The most common reasons for choosing mephedrone over other substances were better high from the drug and peer pressure. There were no associations between sociodemographic factors with the severity of SUD-M. Around 40% of the patients with SUD-M had psychiatric comorbidity. Psychotic disorders and anxiety symptoms were most common. Family history of substance use, comorbid substance use, and comorbid psychiatric disorders were directly related to the severity of SUD-M. Conclusions: This was a cross‑sectional study with a relatively smaller sample size of self‑nominating participantslimiting the generalizability of findings to a wider population. Therapeutic implication of this finding is that prompt attention and treatment of the comorbid psychiatric disorder is essential while treating patients with SUD-M. Further population-based studies are recommended for a better understanding of the burden of SUD-M.
    • Spinal motor neurite outgrowth over glial scar inhibitors is enhanced by coculture with bone marrow stromal cells

      Wright, Karina; Johnson, William Eustace Basil; Uchida, Kenzo; Bara, Jennifer J.; Roberts, Sally; Masari, Wagih E.; Aston University; Keele University
      BACKGROUND CONTEXT: Transplantation of bone marrow cells into spinal cord lesions promotes functional recovery in animal models, and recent clinical trials suggest possible recovery also in humans. The mechanisms responsible for these improvements are still unclear. PURPOSE: To characterize spinal cord motor neurite interactions with human bone marrow stromal cells (MSCs) in an in vitro model of spinal cord injury (SCI). STUDY DESIGN/SETTING: Previously, we have reported that human MSCs promote the growth of extending sensory neurites from dorsal root ganglia (DRG), in the presence of some of the molecules present in the glial scar, which are attributed with inhibiting axonal regeneration after SCI. We have adapted and optimized this system replacing the DRG with a spinal cord culture to produce a central nervous system (CNS) model, which is more relevant to the SCI situation. METHODS: We have developed and characterized a novel spinal cord culture system. Human MSCs were cocultured with spinal motor neurites in substrate choice assays containing glial scar–associated inhibitors of nerve growth. In separate experiments, MSC-conditioned media were analyzed and added to spinal motor neurites in substrate choice assays. RESULTS: As has been reported previously with DRG, substrate-bound neurocan and Nogo-A repelled spinal neuronal adhesion and neurite outgrowth, but these inhibitory effects were abrogated in MSC/spinal cord cocultures. However, unlike DRG, spinal neuronal bodies and neurites showed no inhibition to substrates of myelin-associated glycoprotein. In addition, the MSC secretome contained numerous neurotrophic factors that stimulated spinal neurite outgrowth, but these were not sufficient stimuli to promote spinal neurite extension over inhibitory concentrations of neurocan or Nogo-A. CONCLUSIONS: These findings provide novel insight into how MSC transplantation may promote regeneration and functional recovery in animal models of SCI and in the clinic, especially in the chronic situation in which glial scars (and associated neural inhibitors) are well established. In addition, we have confirmed that this CNS model predominantly comprises motor neurons via immunocytochemical characterization. We hope that this model may be used in future research to test various other potential interventions for spinal injury or disease states
    • SS-31 attenuates TNF-α induced cytokine release from C2C12 myotubes

      Nye, Gareth; Lightfoot, Adam; Sakellariou, Giorgos; McArdle, Francis; Jackson, Malcolm; Griffiths, Richard; McArdle, Anne; University of Liverpool (Elsevier, 2015-08-10)
      TNF-α is a key inflammatory mediator and is proposed to induce transcriptional responses via the mitochondrial generation of Reactive Oxygen Species (ROS). The aim of this study was to determine the effect of TNF-α on the production of myokines by skeletal muscle. Significant increases were seen in the release of IL-6, MCP-1/CCL2, RANTES/CCL5 and KC/CXCL1 and this release was inhibited by treatment with Brefeldin A, suggesting a golgi-mediated release of cytokines by muscle cells. An increase was also seen in superoxide in response to treatment with TNF-α, which was localised to the mitochondria and this was also associated with activation of NF-κB. The changes in superoxide, activation of NF-kB and release of myokines were attenuated following pre-treatment with SS-31 peptide indicating that the ability of TNF-α to induce myokine release may be mediated through mitochondrial superoxide, which is, at least in part, associated with activation of the redox sensitive transcription factor NF-kB.
    • Standards and core components for cardiovascular disease prevention and rehabilitation; BACPR

      Cowie, Aynsley; Buckley, John P.; Doherty, Patrick; Furze, Gill; Hayward, Jo; Jones, Jennifer; Speck, Linda; Dalal, Hayes; Mills, Joseph; University Centre Shrewsbury (BMJ, 2019-01-30)
      In 2017, the British Association for Cardiovascular Prevention and Rehabilitation published its official document detailing standards and core components for cardiovascular prevention and rehabilitation. Building on the success of previous editions of this document (published in 2007 and 2012), the 2017 update aims to further emphasise to commissioners, clinicians, politicians and the public the importance of robust, quality indicators of cardiac rehabilitation (CR) service delivery. Otherwise, its overall aim remains consistent with the previous publications—to provide a precedent on which all effective cardiovascular prevention and rehabilitation programmes are based and a framework for use in assessment of variation in service delivery quality. In this 2017 edition, the previously described seven standards and core components have both been revised to six, with a greater focus on measurable clinical outcomes, audit and certification. The principles within the updated document underpin the six-stage pathway of care for CR, and reflect the extensive evidence base now available within the field. To help improve current services, close collaboration between commissioners and CR providers is advocated, with use of the CR costing tool in financial planning of programmes. The document specifies how quality assurance can be facilitated through local audit, and advocates routine upload of individual-level data to the annual British Heart Foundation National Audit of Cardiac Rehabilitation, and application for national certification ensuring attainment of a minimum quality standard. Although developed for the UK, these standards and core components may be applicable to other countries.
    • Stent Frame Movement Following Endovascular Aneurysm Sealing in the Abdominal Aorta

      Yafawi, Asma; McWilliams, Richard G.; Fisher, Robert K.; England, Andrew; Karouki, Maria; Torella, Francesco (SAGE Publications, 2018-11-28)
    • Stent Migration Following Endovascular Sealing of Abdominal Aortic Aneurysms

      Yafawi, Asma; McWilliams, Richard G.; Fisher, Robert K.; England, Andrew; Karouki, Maria; Torella, Francesco (Elsevier, 2019-12-09)
    • Submaximal Exercise Testing in Cardiovascular Rehabilitation Settings (BEST Study)

      Reed, Jennifer L; Cotie, LM; Cole, CA; Harris, Jennifer; Moran, B; Scott, K; Buckley, John P; Pipe, Andrew L; University of Ottawa, University Centre Shrewsbury/Chester
      Abstract BACKGROUND: This study compared changes in measured versus predicted peak aerobic power (V̇O2 peak) following cardiovascular rehabilitation (CR). Peak cardiopulmonary exercise testing (CPET) results were compared to four V̇O2 peak estimation methods: the submaximal modified Bruce treadmill, Astrand-Ryhming cycle ergometer, and Chester step tests, and the Duke Activity Status Index (DASI). METHODS: Adults with cardiovascular disease (CVD) who completed a 12-week CR program were assessed at baseline and 12 weeks follow-up. CPET, the DASI and three subsequent submaximal exercise tests were performed in a random order. RESULTS: Of the 50 adults (age: 57 ± 11 years) who participated, 46 completed the 12-week CR program and exercise tests. At baseline 69, 68, and 38% of the treadmill, step and cycle tests were successfully completed, respectively. At follow-up 67, 80, and 46% of the treadmill, step and cycle tests were successfully completed, respectively. No severe adverse events occurred. Significant improvements in V̇O2 peak were observed with CPET (3.6 ± 5.5 mL.kg-1.min-1, p < 0.001) and the DASI (2.3 ± 4.2 mL.kg-1.min-1, p < 0.001). Bland-Altman plots of the change in V̇O2 peak between CPET and the four V̇O2 peak estimation methods revealed the following: a proportional bias and heteroscedastic 95% limits of agreement (95% LoA) for the treadmill test, and for the cycle and step tests and DASI, mean bias' and 95% LoA of 1.0 mL.kg-1.min-1 (21.3, -19.3), 1.4 mL.kg-1.min-1 (15.0, -12.3) and 1.0 mL.kg-1.min-1 (13.8, -11.8), respectively. CONCLUSION: Given the greater number of successful tests, no serious adverse events and acceptable mean bias, the step test appears to be a valid and safe method for assessing group-level mean changes in V̇O2 peak among patients in CR. The DASI also appears to be a valid and practical questionnaire. Wide limits of agreement, however, limit their use to predict individual-level changes. Copyright © 2020 Reed, Cotie, Cole, Harris, Moran, Scott, Terada, Buckley and Pipe. KEYWORDS: cardiovascular diseases; exercise test; physiology; rehabilitation; submaximal
    • Systematic review and meta-analysis of group cognitive behavioural psychotherapy for sub-clinical depression

      Krishna, Murali; Lepping, Peter; Jones, Steven; Lane, Stephen; University of Chester (Elsevier, 2015-06-04)
      Key Points • Group CBT for patients with sub-threshold depression has a significant effect on depressive symptomatology at post treatment in both working age and older adult population. • Group CBT does not appear to reduce the incidence of major depressive disorders. • Group CBT has minimal or no effect on depressive symptomatology during follow-up. The article considers group psychotherapy in sub-threshold depression to investigate if group psychological interventions reduce depressive symptoms post treatment, and whether these interventions result in a reduced incidence of new cases of major depressive disorder.
    • 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 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