Chester Medical School run research programmes jointly with the Countess of Chester Hospital NHS Foundation Trust (COCH) and other hospital trusts that are relevant at regional, national and international level.

Recent Submissions

  • An Audit on the Adherence to Antipsychotic Prescription Policy for the Management of Delirium in the Medical Wards.

    Simiyon, M; Loo, J,L; Baker, C; Lepping, P; Jones, S; Betsi Cadwaladr University Health Board; University of Chester (Cambridge University Press, 2022-06-20)
    This audit aimed to assess the adherence to the antipsychotic policy for delirium in the medical wards. It aimed to assess compliance with each of the guidelines mentioned in the health board’s policy which is based on the National Institute for Health and Cares Excellence (NICE) guidelines.
  • A pilot study of a single intermittent arm cycling exercise programme on people affected by Facioscapulohumeral dystrophy (FSHD)

    editor: Vousden, George; Philp, Fraser; orcid: 0000-0002-8552-7869; email:; Kulshrestha, Richa; Emery, Nicholas; Arkesteijn, Marco; Pandyan, Anand; Willis, Tracey (Public Library of Science, 2022-06-24)
    For patients affected by Facioscapulohumeral dystrophy (FSHD), alternate methods for increasing physical activity engagement that may benefit shoulder function and wider health are needed. Arm cycling has been proposed as a potential method for achieving this although dosage parameters and evidence is limited. The aim of this study was to conduct a pilot study evaluating the effect of a single intermittent arm cycling exercise programme on people affected by FSHD. People with confirmed genetic diagnosis of FSHD between the ages 18–60 years were recruited to attend a single session for the exercise intervention (5 exercise efforts lasting 2 minutes each with 30 seconds of rest between each effort). Prior to exercise, measures of shoulder function (Oxford shoulder score), strength and range of movement were recorded. During the exercise participants were video recorded to quantify range of movement and extract movement profile features. Participants comments were recorded and followed up four days later to check for adverse events. Fifteen participants, (6F:9M) were recruited with median (IQR) Oxford Shoulder Scores of 25 (18 to 39). All participants successfully completed the exercise intervention with only transient symptoms consistent with exercise being reported and achieving a median (IQR) rate of perceived exertion scores of 13 (12 to 13). Movement profile data was available for 12 out of 15 participants and suggests that exercise intensity did not compromise movement. An association between strength and shoulder function (R2 = 0.5147), Rate of perceived exertion (RPE) of the final effort against shoulder function and strength (R2 = 0.2344 and 0.1743 respectively) was identified. Participant comments were positive regarding the exercise intervention. Our study demonstrates that an intermittent arm cycling programme is feasible for people affected by FSHD. Further work is needed to evaluate physiological responses to exercise across variations in programme variables and equipment set up in a larger sample of people affected by FSHD.
  • Constructing and conceptualizing suicide and self-harm

    Jones, Steven; Nathan, Taj; University of Chester
    The chapter on ‘’ Contextualising suicide and self-harm’ ’provides an overview of suicide and self-harm, with particular focus to social theory, epidemiology, societal attitudes, law and ethics, and management strategies. Suicide and self-harm rates, and are explored from a national and international perspectives. The authors examine self-harm and suicide grounded in theory and practice, taking account of both societal and individual domains. The aim is to explore the conceptualisation of suicide and self-harm and relate it to the evidence base. The chapter commences with suicide models and aims to equip the reader with a framework to explore this sensitive topic; Durkheim is used to allow readers to challenge their knowledge and attitudes. Suicide and self-harm statistics are reported before offering some context to them. Suicide is a human tragedy and no amount of theories, statistics or facts will change its far-reaching impact. We have attempted to address the consequences of self-harm and suicide on the individual and their family unit. Media portrayal, assessment, prevention strategies, legislation and knowledge and attitudes to suicide are explored.
  • Non-Alcoholic Fatty Liver Disease (NAFLD) and Potential Links to Depression, Anxiety, and Chronic Stress

    Shea, Sue; Lionis, Christos; Kite, Chris; Atkinson, Lou; Chaggar, Surinderjeet; Randeva, Harpal S; Kyrou, Ioannis; University of Warwick; University Hospitals Coventry and Warwickshire NHS Trust; University of Crete; University of Chester; Coventry University; Aston University; Forum Health Centre; Agricultural University of Athens (MDPI, 2021-11-16)
    Non-alcoholic fatty liver disease (NAFLD) constitutes the most common liver disease worldwide, and is frequently linked to the metabolic syndrome. The latter represents a clustering of related cardio-metabolic components, which are often observed in patients with NAFLD and increase the risk of cardiovascular disease. Furthermore, growing evidence suggests a positive association between metabolic syndrome and certain mental health problems (e.g., depression, anxiety, and chronic stress). Given the strong overlap between metabolic syndrome and NAFLD, and the common underlying mechanisms that link the two conditions, it is probable that potentially bidirectional associations are also present between NAFLD and mental health comorbidity. The identification of such links is worthy of further investigation, as this can inform more targeted interventions for patients with NAFLD. Therefore, the present review discusses published evidence in relation to associations of depression, anxiety, stress, and impaired health-related quality of life with NAFLD and metabolic syndrome. Attention is also drawn to the complex nature of affective disorders and potential overlapping symptoms between such conditions and NAFLD, while a focus is also placed on the postulated mechanisms mediating associations between mental health and both NAFLD and metabolic syndrome. Relevant gaps/weaknesses of the available literature are also highlighted, together with future research directions that need to be further explored.
  • 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.
  • 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.
  • A single dose of ChAdOx1 Chik vaccine induces neutralising antibodies against four chikungunya virus lineages in a phase 1 clinical trial

    Folegatti, Pedro M.; Harrison, Kate; Preciado-Llanes, Lorena; Ramos Lopez, Fernando; Bittaye, Mustapha; Kim, Young Chan; Flaxman, Amy; Bellamy, Duncan; Makinson, Rebecca; Sheridan, Jonathan; et al. (Nature Research, 2021-07-30)
    Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18–50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and Tcell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.
  • Attitudes of Female Warders towards inmate who self-harm: A pilot Exploratory Study from an Inner-city Prison in South India

    Jones, Steven; Kumar, Pradeep; Eost-Telling, Charlotte; Kirshna, Murali; University of Chester (The Indian Society of Criminology; National Law University Delhi, 2020-07-01)
    Self-harm is a global public health challenge. The management and treatment of those who self-harm is emotionally challenging, and can sometimes manifest in negative attitudes amongst staff who provide care. Health professional’s attitudes towards deliberate self-harm have been studied globally, however, evidence regarding prison staff attitudes is sparse, and particularly lacking in India. The primary aim of this study was to explore the attitudes of female prison warders towards prison inmates who self-harm in an Indian setting. A cross-sectional survey using a questionnaire to measure knowledge and attitudes was administered to prison warders from one city prison in South India. Out of the 210 approached to participate, 170 female warders completed the survey questionnaire. In general, sociodemographic factors of the prison warders were unrelated to their attitudes towards self-harm, and a negligible few had received any training specific to self-harm. A series of educational and skills recommendations have been developed from the study, which can be used to inform intervention initiatives and further, provide a basis for cross-cultural professional comparison studies. Current resources, cultures, practice and context must be considered in any future interventions aimed at progressing the evidence base further. In addition, training and education for staff should include information on knowledge and attitudes about causes, reasons, motivations, forms and purpose of self-harm. Records of staff responses to those who self-harm, irrespective of setting, should include assessment, management, interventions undertaken and incorporated daily practice. Importantly, this work may influence prisoner treatment outcomes and is worthy of further study.
  • A massively multi-scale approach to characterizing tissue architecture by synchrotron micro-CT applied to the human placenta

    Tun, W. M.; orcid: 0000-0003-0991-8785; Poologasundarampillai, G.; orcid: 0000-0002-8498-323X; Bischof, H.; Nye, Gareth; King, O. N. F.; orcid: 0000-0002-6152-7207; Basham, M.; orcid: 0000-0002-8438-1415; Tokudome, Y.; Lewis, R. M.; orcid: 0000-0003-4044-9104; Johnstone, E. D.; Brownbill, P.; orcid: 0000-0002-8328-7072; email:; et al. (The Royal Society, 2021-06-02)
    Multi-scale structural assessment of biological soft tissue is challenging but essential to gain insight into structure–function relationships of tissue/organ. Using the human placenta as an example, this study brings together sophisticated sample preparation protocols, advanced imaging and robust, validated machine-learning segmentation techniques to provide the first massively multi-scale and multi-domain information that enables detailed morphological and functional analyses of both maternal and fetal placental domains. Finally, we quantify the scale-dependent error in morphological metrics of heterogeneous placental tissue, estimating the minimal tissue scale needed in extracting meaningful biological data. The developed protocol is beneficial for high-throughput investigation of structure–function relationships in both normal and diseased placentas, allowing us to optimize therapeutic approaches for pathological pregnancies. In addition, the methodology presented is applicable in the characterization of tissue architecture and physiological behaviours of other complex organs with similarity to the placenta, where an exchange barrier possesses circulating vascular and avascular fluid spaces.
  • Physical health impairment, disability and suicidal intent among self-harm survivors in South India

    Jones, Steven; Somashekar, R; Bharath, D.U; Maiji, Sumanth M; Taylor, Lou; Nagaraj, Santhosh; Krishna, Murali; Mysore Medical College and Research Institute; University of Chester; CSI Holdsworth Memorial Hospital; FRAMe; Viveka Hospital (Medip Academy, 2021-04-27)
    Background: Suicide is major public health concern in India. There are limited data examining the relationship between health impairment, disability and severity of suicidal intent. The aim of the study was to examine the associations of health impairment and disability with severity of suicidal intent among survivors following an act of self-harm. Methods: A pilot exploratory study of 453 self-harm survivors from a specialist hospital in South India. Sociodemographics, physical health impairment, disability (WHO Disability Schedule-II), suicidal intent, (Pierce suicide intent scale) and mental disorders were studied. Results: Arthritis was the most common physical impairment among self-harm survivors followed by gastrointestinal, sensory impairment and difficulty with mobilization. Nearly 10% of participants had some degree of functional impairment, with 38% experiencing severe physical pain in the week prior to self-harm. Past history of depression treatment, age, education and occupation influenced positively PSIS scores. There were significant associations between suicidal intent and disability. Conclusions: Indian self-harm survivors indicated complex relationships between physical health, disability and suicidal intent. Understanding these associations may help to develop suicide prevention strategies. Our findings suggest a need for integrating a comprehensive of physical health assessment in self harm survivors.
  • Comment on PP2A inhibition sensitizes cancer stem cells to ABL tyrosine kinase inhibitors in BCR-ABL human leukemia

    Perrotti, D; Agarwal, A; Lucas, Claire; Narla, g; Nevanini, p; Odero, m; Ruvolo, p; Verrills, n; University of Maryland; Imperial College London; Oregon Health and Science University; University of Chester; University of Michigan; University of Southern California; University of Navarra; MD Anderson Cancer Center; University of Newcastle (American Association for the Advancement of Science, 2019-07-17)
    LB100 does not sensitize CML stem cells to tyrosine kinase inhibitor–induced apoptosis.
  • Discovery of a Novel CIP2A Variant (NOCIVA) with clinical relevance in predicting TKI resistance in myeloid leukemias

    Makela, Eleonora; Pavic, Karolina; Varila, Taru M; Salmenniemi, Urpu; Löyttyniemi, Eliisa; Nagelli, Srikar G; Ammunét, Tea; Kähäri, Veli-Matti; Clark, Richard E; Elo, Laura L; et al.
    Purpose: Cancerous inhibitor of PP2A (CIP2A) is an oncoprotein that inhibits the tumor suppressor PP2A-B56a. However, CIP2A mRNA variants remain uncharacterized. Here, we report the discovery of a CIP2Asplicing variant, NOCIVA (NOvel CIp2a VAriant). Experimental Design: Characterization of CIP2A variants was performed by both 3' and 5' rapid amplification of cDNA ends from cancer cells. The function of NOCIVA was assessed by structural and molecular biology approaches. Its clinical relevance was studied in an acute myeloid leukemia (AML) patient cohort and two independent chronic myeloid leukemia (CML) cohorts. Results: NOCIVA contains CIP2A exons 1-13 fused to 349 nucleotides from CIP2A intron 13. Intriguingly, the first 39 nucleotides of the NOCIVA-specific sequence are in the coding frame with exon 13 of CIP2A and code for a 13 amino acid peptide tail nonhomologous to any known human protein sequence. Therefore, NOCIVA translates to a unique human protein. NOCIVA retains the capacity to bind to B56a, but whereas CIP2A is predominantly a cytoplasmic protein, NOCIVA translocates to the nucleus. Indicative of prevalent alternative splicing from CIP2A to NOCIVA in myeloid malignancies, AML and CML patient samples overexpress NOCIVA but not CIP2A mRNA. In AML, a high NOCIVA/CIP2A mRNA expression ratio is a marker for adverse overall survival. In CML, high NOCIVA expression is associated with inferior event-free survival among imatinib-treated patients, but not among patients treated with dasatinib or nilotinib. Conclusions: We discovered novel variant of the oncoprotein CIP2A and its clinical relevance in predicting tyrosine kinase inhibitor therapy resistance in myeloid leukemias.
  • 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:; Pickard, Mark R.; email:; Johnson, William E. B.; email: (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.
  • Acute glycaemic management before, during and after exercise for cardiac rehabilitation participants with diabetes mellitus; a joint statement of the British and Canadian Associations of Cardiovascular Prevention and Rehabilitation, the International Council for Cardiovascular Prevention and Rehabilitation and the British Association of Sport and Exercise Sciences

    Buckley, J.P.; Riddell, Michael; Mellor, Duane; Bracken, Richard; Ross, Marie-Kristelle; LaGerche, Andre; Poirier, Paul; University of Chester; University College London; York University, Toronto; LMC Healthcare; Aston University; Swansea University College of Engineering; Laval University; Baker Heart and Diabetes Institute; St Vincent's Hospital Melbourne; Institut universitaire de cardiologie et de pneumologie de Québec (BMJ, 2020-12-23)
    Type 1 (T1) and type 2 (T2) diabetes mellitus (DM) are significant precursors and comorbidities to cardiovascular disease and prevalence of both types is still rising globally. Currently,~25% of participants (and rising) attending cardiac rehabilitation in Europe, North America and Australia have been reported to have DM (>90% have T2DM). While there is some debate over whether improving glycaemic control in those with heart disease can independently improve future cardiovascular health-related outcomes, for the individual patient whose blood glucose is well controlled, it can aid the exercise programme in being more efficacious. Good glycaemic management not only helps to mitigate the risk of acute glycaemic events during exercising, it also aids in achieving the requisite physiological and psycho-social aims of the exercise component of cardiac rehabilitation (CR). These benefits are strongly associated with effective behaviour change, including increased enjoyment, adherence and self-efficacy. It is known that CR participants with DM have lower uptake and adherence rates compared with those without DM. This expert statement provides CR practitioners with nine recommendations aimed to aid in the participant’s improved blood glucose control before, during and after exercise so as to prevent the risk of glycaemic events that could mitigate their beneficial participation.
  • 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.
  • 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.
  • 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.
  • Occurrence of chemical pollutants in major e-waste sites in West Africa and usefulness of cytotoxicity and induction of ethoxyresorufin-O-deethylase (EROD) in determining the effects of some detected brominated flame retardants and e-waste soil-derived extracts.

    Eze, Chukwuebuka ThankGod; orcid: 0000-0001-8076-2926; email:; Michelangeli, Francesco; Otitoloju, Adebayo Akeem; Eze, Obianuju Oluchukwu; Ibraheem, Omodele; Ogbuene, Emeka Bright; Ogunwole, Germaine Akinola (2020-10-25)
    We investigated the occurrence of chemical pollutants in major e-waste sites in West Africa and usefulness of cytotoxicity and induction of ethoxyresorufin-O-deethylase (EROD) in determining the effects of some detected brominated flame retardants (BFRs) and e-waste soil-derived extracts. Analysis of the e-waste site samples using AAS and GC-MS techniques revealed the presence of a range of toxic metals as well as persistent and toxic organic pollutants, respectively, in the vicinity of the e-waste sites. As expected, the occurrence (%) of all the detected chemical pollutants in experimental soils significantly (P < 0.05) differs from occurrence (%) in control soil. The calculated LC values on RBL-2H3 cells of the detected tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCD) were 3.75 μM and 4.2 μM, respectively. Tribromophenol (TBP), dibromobiphenyl (DBB), and decabromodiphenyl ether (DBDE) were remarkably less toxic on RBL-2H3 cells compared with TBBPA and HBCD as they did not reduce RBL-2H3 cell viability below 50% in the tested concentration range (0-20 μM). The study revealed that TBBPA and HBCD could induce significant RBL-2H3 cell death through caspase-dependent apoptosis. The study further shows that the cytotoxicity of some of these BFRs could increase synergistically when in mixtures and potentially activate inflammation through the stimulation of mast cell degranulation. The e-waste soil-derived extracts induced a concentration-dependent increase in EROD activity in the exposed RTG-W1 cells. Ultimately, nonpolar extracts had higher EROD-inducing potency compared with polar extracts and hence suggesting the presence in higher amounts of AhR agonists in nonpolar e-waste soil-derived extracts than polar extracts. Overall, there is urgent need for actions in order to improve the environmental quality of the e-waste sites.
  • 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.
  • History of traction

    Flynn, Sandra (Elsevier, 2020-10-01)

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