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

  • Introducing open book examinations in clinical education: A case study

    Smith, Peter M.; Bowles, Joanne; Jellicoe, Mark; Mathur, Manu; Molyneux, Lorraine; Randell, Leigh-Ann; Smith, Richard N.; Valappil, Sabeel P.; University of Liverpool; The University of Law; Queen Mary University of London; University of Chester (Liverpool University Press, 2023-01-18)
    During the recent COVID-19 pandemic, in common with educators across the Higher Education sector, the School of Dentistry at the University of Liverpool reimagined the learning and assessment strategy by moving from proctored closed-book assessment to largely unmonitored open-book examinations (OBE). This article discusses understandings from an educator perspective following our implementation of OBE. The educator perspective discussed here indicates that OBE have the potential to be an authentic and acceptable form of assessment, but that some reframing of attitudes towards assessment from all stakeholders and their approaches to assessment is necessary when developing these innovative types of assessment.
  • Antibacterial, Remineralising and Matrix Metalloproteinase Inhibiting Scandium-doped Phosphate Glasses for Treatment of Dental Caries

    Valappil, Sabeel P.; Abou Neel, Ensanya A.; Pickup, David M.; Burden, Emily; Sahdev, Rohan; Miles, Emma J; Cooper, Lee; Ansari, Tahera I; Hanna, John V; Higham, Susan M.; et al. (Elsevier, 2021-11-22)
    Objectives: Antibiotic resistance is increasingly a growing global threat. This study aimed to investigate the potential use of newly developed scandium-doped phosphate-based glasses (Sc-PBGs) as an antibacterial and anticariogenic agent through controlled release of Sc3+ ions. Methods: Sc-PBGs with various calcium and sodium oxide contents were produced and characterised using thermal and spectroscopic analysis. Degradation behaviour, ion release, antibacterial action against Streptococcus mutans, anti-matrix metalloproteinase-2 (MMP-2) activity, remineralisation potential and in vivo biocompatibility were also investigated. Results: The developed glass system showed linear Sc3+ ions release over time. The released Sc3+ shows statistically significant inhibition of S. mutans biofilm (1.2 log10 CFU reduction at 6 h) and matrix metalloproteinase-2 (MMP-2) activity, compared with Sc-free glass and positive control. When Sc-PBGs were mounted alongside enamel sections, subjected to acidic challenges, alternating hyper- and hypomineralisation layers consistent with periods of re- and demineralisation were observed demonstrating their potential remineralising action. Furthermore, Sc-PBGs produced a non-toxic response when implanted subcutaneously for 2 weeks in Sprague Dawley rats. Significance: Since Sc3+ ions might act on various enzymes essential to the biological mechanisms underlying caries, Sc-PBGs could be a promising therapeutic agent against cariogenic bacteria.
  • Antibacterial, Remineralizing Zinc Oxide-Doped Phosphate-Based Glasses

    Rajadorai, Sindhuja; Harris, Genevieve; Robinson, Alistair; Miles, Emma J; Roberts, Jonathan; Cooper, Lee; Abou Neel, Ensanya A.; Higham, Susan M.; Flannigan, Norah L; Valappil, Sabeel P.; et al. (Elsevier, 2021-09-11)
    This study reports a novel melt quenched zinc oxide-doped phosphate-based glasses (Zn-PBGs) of varying CaO mol% designated as C11, C12, C13. The glass degradation rate, ions release, antibacterial activity against S. mutans and remineralization potential were investigated. Zn-PBGs showed one order of magnitude higher degradation rate than Zn-free PBG. The highest rate was observed for C11; Na+, Ca2+, Zn2+ and P5+ release followed the same trend. The higher the Zn2+ release, the greater the S. mutans growth inhibition. C11 showed significantly lower mineral loss from enamel than positive and negative controls. Zn-PBGs could be used to reverse enamel demineralization.
  • The cariogenic effect of starch on oral microcosm grown within the dual constant depth film fermenter

    Roberts, Jonathan M.; Bradshaw, David J.; Lynch, Richard J.M.; Higham, Susan M.; Valappil, Sabeel P.; University of Liverpool; GlaxoSmithKline Consumer Healthcare; University of Chester (Public Library of Science, 2021-10-20)
    Evidence on the link between starch intake and caries incidence is conflicting, therefore the cariogenicity of starch compared with sucrose was explored using a dual Constant Depth Film Fermenter (dCDFF) biotic model system. Bovine enamel discs were used as a substrate and the dCDFF was inoculated using human saliva. CDFF units were supplemented with artificial saliva growth media at a constant rate to mimic resting salivary flow rate over 14 days. The CDFF units were exposed to different conditions, 2 % sucrose or 2 % starch 8 times daily and either no additional fluoride or 1450 ppm F- twice daily. Bovine enamel discs were removed at intervals (days 3, 7, 10 and 14) for bacterial enumeration and enamel analysis using Quantitative Light Induced Fluorescence (QLF) and Transverse Microradiography (TMR). Results showed that in the absence of fluoride there was generally no difference in mineral loss between enamel exposed to either sucrose or starch when analysed using TMR and QLF (P > 0.05). In the presence of fluoride by day 14 there was significantly more mineral loss under starch than sucrose when analysed with TMR (P < 0.05). It was confirmed that starch and sucrose are similarly cariogenic within the dCDFF in the absence of fluoride. With the aid of salivary amylase, the bacteria utilise starch to produce an acidic environment similar to that of bacteria exposed to sucrose only. In the presence of fluoride, starch was more cariogenic which may be due to the bacteria producing a more hydrophobic intercellular matrix lowering the penetration of fluoride through the biofilm. This is significant as it indicates that the focus on sugars being the primary cause of caries may need re-evaluating and an increase in focus on carbohydrates is needed as they may be similarly cariogenic as sugars if not more so.
  • Quantifying the Demineralisation of Enamel Using a Hyperspectral Camera Measuring Fluorescence Loss

    Roberts, Jonathan M.; Bradshaw, David J.; Lynch, Richard J.M.; Higham, Susan M.; Valappil, Sabeel P.; University of Liverpool; GlaxoSmithKline Consumer Healthcare; University of Chester (Elsevier, 2021-10-30)
    Background The gold standard for quantifying mineral loss of enamel is transverse microradiography (TMR) and is complimented by the non-destructive quantitative light induced fluorescence (QLF) which measures changes in autofluorescence. Fluorescence loss has been shown to correlate with mineral loss. Building upon the established method, the use of hyperspectral fluorescence imaging (HI) allows the capture of a broader range of wavelengths to quantify fluorescence changes more accurately. Methods Bovine Enamel was demineralised within the dual constant depth film fermenter over 14 days and analysed using TMR, QLF and HI. The mineral change values were compared using Pearson's Correlation Coefficient. Results The analysis showed a statistically significant correlation that was equal between TMR and HI (r = 0.844) and TMR and QLF (r = 0.844), but weaker between QLF and HI (r = 0.811). Conclusions The correlations indicate that HI is a promising valid non-destructive method for quantifying mineral loss from bovine enamel that is as accurate as QLF and complements TMR.
  • Use of long-acting injectable antiretroviral agents for human immunodeficiency Virus: A review

    Ariyo, Olumuyiwa E.; Jones, Christopher E.; Federal Teaching Hospital, Nigeria; University of Chester (Elsevier, 2021-11-23)
    The development of potent antiretroviral drugs has significantly reduced morbidity and mortality associated with human immunodeficiency virus infection, however, the effectiveness of these medications depends upon consistent daily oral intake. Non-adherence can lead to the emergence of resistance, treatment failure and disease progression. This has necessitated the development of long-acting antiretroviral formulations administrable via an infrequent dosing regimen. Long-acting injectable forms of cabotegravir and rilpivirine have reached various stages in clinical trials both for the treatment and prevention of HIV. Other long-acting agents are at various stages of development. This review evaluates the current research on the development of long-acting injectable antiretroviral agents for the treatment and prevention of HIV.
  • Short Research Article: Do demographic, socioeconomic and clinical characteristics influence the number of psychological intervention sessions attended by young people in need of mental health care?

    Meddings, John; Harries, Anthony D; Michelet, Felix; Nall-Evans, Sharleen; Pender, Fiona; Jaydeokar, Sujeet (2022-12-22)
    A cohort study using secondary data assessed associations between baseline characteristics and psychological sessions attended in young persons discharged from a Children and Young People's Mental Health Service in 2019. There were 584 persons who attended a median of seven sessions. On multivariable regression analysis, males attended fewer sessions than females, young people from more affluent communities attended more sessions than those from poorer communities and those presenting with eating disorders and self-harm in particular attended more sessions than those with anxiety. Addressing why these associations occur may improve mental health care in young persons. [Abstract copyright: © 2022 Association for Child and Adolescent Mental Health.]
  • Care givers experiences of caring for people with intellectual disability and dementia: a qualitative evidence synthesis

    Acton, Danny; Jones, Steven; Jaydeokar, Sujeet; Cheshire and Wirral Partnership NHS Foundation Trust; Centre for Autism Neurodevelopmental Disorders and Intellectual Disability (CANDDID); University of Chester (Emerald, 2023-01-20)
    This paper aims to identify the lived experience of anxiety from people with intellectual disabilities and being co-design partners in developing a multi component approach to the management of anxiety. Design/methodology/approach The development of an anxiety manual and programme was part of a service development which allowed existing and establish psychological therapies be adapted for people with intellectual disabilities. A qualitative approach was used to understand the views of people who experience anxiety on a daily basis. The feedback generated was used to make modifications to the manuals and anxiety management programme. Findings The study has demonstrated the value of involving people with intellectual disabilities in co-production of an anxiety management programme. Additional findings identified the rea life challenges and experiences of the impact anxiety has on people’s lives.
  • Ideal models of good inpatient care for adults with intellectual disability: Lessons from England

    Burrows, Lisa; Page, Georgia; Plugaru, Elena; Kent, Bridie; Odiyoor, Mahesh; Jaydeokar, Sujeet; Williams, Jonathan; Elliot, Kevin; Laugharne, Richard; Shankar, Rohit; orcid: 0000-0002-1183-6933 (SAGE Publications, 2022-12-04)
    Background: In recent years, a significant proportion of inpatient facilities for people with intellectual disabilities and/or autism has been de-commissioned in England, This has resulted in individuals with intellectual disabilities being sent to distant hospitals far away from their families and carers leading to challenges in follow-up, community care and interventions. The impact of de-institutionalisation, has often caused patient trauma, family distress and subsequent discharge difficulties. Not every individual with intellectual disabilities and/or autism requires inpatient care but inpatient care when needed has to be local, adequate and appropriate. Aims: To evaluate current evidence of utility of inpatient models for people with intellectual disabilities and outline best clinical practice. Method: PubMed, CINAHL, EMBASE, Cochrane Library, Scopus, Web of Science were searched with key search terms. The search was conducted by the information specialist and identified abstracts screened further for inclusion criteria, methodological issues, and other appropriate characteristics. Twenty-three papers were included in the rapid review. Papers shortlisted had the inclusion criteria applied against the full text version independently by two reviewers. Disagreements regarding eligibility of studies was resolved by discussion and consensus within the project team. Key data related to in-patient models of care was extracted from the included papers, which included year of study, design, study objectives, target population, method/s tested, outcomes reported, country of study/studies, and results. Data extraction was performed by two reviewers and reviewed by the project team. Results: From the review of services for people with intellectual disabilities, we came across four broad models/frameworks/approaches. Evidence on what worked for inpatient service provision tended to be based on models developed and implemented locally. Conclusions: We make recommendations for the best clinical practice and standards. Both clinical service providers and policymakers need to be aware of specific needs of individuals with intellectual disability and/or autism.
  • Radiation-mediated supply of genetic variation outweighs the effects of selection and drift in Chernobyl Daphnia populations

    Goodman, Jessica; Brand, June; Laptev, Gennady; Auld, Stuart, K, J, R; University of Stirling; Ukrainian HydroMeteorological Intstitute; University of Chester (Wiley, 2022-01-19)
    Populations experiencing varying levels of ionizing radiation provide an excellent opportunity to study the fundamental drivers of evolution. Radiation can cause mutations and thus supply genetic variation; it can also selectively remove individuals that are unable to cope with the physiological stresses associated with radiation exposure, or non-selectively cull swathes of the population, reducing genetic variation. Since the nuclear power plant explosion in 1986, the Chernobyl area has experienced a spatially heterogeneous exposure to varying levels of ionizing radiation. We sampled Daphnia pulex (a freshwater crustacean) from lakes across the Chernobyl area, genotyped them at ten microsatellite loci and also calculated the current radiation dose rates. We then investigated whether the pattern of genetic diversity was positively associated with radiation dose rates, consistent with radiation-mediated supply of de novo mutations, or negatively associated with radiation dose rates, as would be expected with strong radiation-mediated selection. We found that measures of genetic diversity, including expected heterozygosity and mean allelic richness (an unbiased indicator of diversity), were significantly higher in lakes that experienced the highest radiation dose rates. This suggests that mutation outweighs selection as the key evolutionary force in populations exposed to high radiation dose rates. We also found significant but weak population structure, indicative of low genetic drift and clear evidence for isolation-by-distance between populations. This further suggests that gene flow between nearby populations is eroding population structure and that mutational input in high radiation lakes could, ultimately, supply genetic variation to lower radiation sites.
  • Right cardiac chambers echo-bubble contrast in a patient with decompression sickness: A case report and a literature review

    Harfoush, Allam; Ramadan, Mohammad; Hamdallah, Hanady; Tishreen University Hospital; University of Chester (Wiley Open Access, 2022-04-14)
    Background: so far there is no available modality to fully confirm the diagnosis, however, the application of echocardiography in suspected DCS cases has been more frequently used, in this case, transthoracic echocardiography (TTE) was used to detect micro-bubbles in the right cardiac chambers and monitor the patient after hyperbaric oxygen therapy (HBOT); which proposes the possible applicability of TTE in diagnosing and monitoring DCS patients. Case presentation: This report describes a 54-year-old fisherman who was referred to the emergency department with dyspnea and mild confusion after rapid ascend of a saturation diving of 50m sea depth. After the initial evaluation, he was assessed using TTE to exclude the presence of structural heart diseases, where it surprisingly showed spontaneous echo contrast inside the right cardiac chambers similar to agitated saline echo testing, the patient then was admitted for HBOT and follow-up; rapid improvement was noticed after the first HBOT session and the TTE findings were fully resolved. Conclusion: TTE could be considered in the initial workup when DCS is suspected, and it might have a role in monitoring DCS patients if echocardiographic findings of bubbles formation were documented in the pre-hyperbaric therapy settings.
  • The Effect of Exercise Training Intensity on VO2max in Healthy Adults: An Overview of Systematic Reviews and Meta-Analyses

    Crowley, Emmet; Powell, Cormac; Carson, Brian P.; Davies, Robert W.; University of Limerick; Sport Ireland National Sports Campus; University of Chester (Hindawi, 2022-02-24)
    This study aimed to evaluate systematic reviews and meta-analyses that have examined the effect of exercise training on VO2max in healthy individuals at different intensities. Five databases were searched: EBSCOhost, MEDLINE/PubMed, SPORTDiscus, Web of Science, and Google Scholar. Eligibility criteria for selecting reviews included systematic reviews and meta-analyses of healthy adults that examined the effect of lower intensity training (LIT) and/or high intensity training (HIT) on VO2max. Eleven reviews met the eligibility criteria. All reviews were of moderate-to-very strong methodological quality. The included reviews reported data from 179 primary studies with an average of 23 ± 10 studies per review. All reviews included in this overview showed that exercise training robustly increased VO2max at all intensities. Three meta-analyses that compared LIT versus HIT protocols on VO2max reported small/moderate beneficial effects for HIT over LIT; however, the beneficial effects of HIT on VO2max appear to be moderated by training variables other than intensity (e.g., training impulse, interval length, training volume, and duration) and participants’ baseline characteristics (e.g., age and fitness levels). Overall, evidence from this overview suggests that the apparent differences between LIT and HIT protocols on VO2max were either small, trivial, or inconclusive, with several methodological considerations required to standardise research designs and draw definitive conclusions.
  • Time to Load Up–Resistance Training Can Improve the Health of Women with Polycystic Ovary Syndrome (PCOS): A Scoping Review

    Kite, Chris; Parkes, Elizabeth; Taylor, Suzan R.; Davies, Robert W.; Lagojda, Lukasz; Brown, James E.; Broom, David R.; Kyrou, Ioannis; Randeva, Harpal S.; University of Wolverhampton; University Hospitals Coventry and Warwickshire NHS Trust; Coventry University; University of Chester; Aston University; University of Warwick; Agricultural University of Athens (MDPI, 2022-09-22)
    Background: Guidelines for the management of polycystic ovary syndrome (PCOS) focus on lifestyle changes, incorporating exercise. Whilst evidence suggests that aerobic exercise may be beneficial, less is known about the effectiveness of resistance training (RT), which may be more feasible for those that have low fitness levels and/or are unable to tolerate/participate in aerobic exercise. Objectives: To identify the available evidence on RT in women with PCOS and to summarise findings in the context of a scoping review. Eligibility criteria: Studies utilising pre-post designs to assess the effectiveness of RT in PCOS; all outcomes were included. Sources of evidence: Four databases (PubMed, CENTRAL, CINAHL and SportDiscus) were searched and supplemented by hand searching of relevant papers/reference lists. Charting methods: Extracted data were presented in tables and qualitatively synthesised. Results: Searches returned 42 papers; of those, 12 papers were included, relating to six studies/trials. Statistical changes were reported for multiple pertinent outcomes relating to metabolic (i.e., glycaemia and fat-free mass) and hormonal (i.e., testosterone and sex hormone-binding globulin) profiles. Conclusions: There is a striking lack of studies in this field and, despite the reported statistical significance for many outcomes, the documented magnitude of changes are small and the quality of the evidence questionable. This highlights an unmet need for rigorously designed/reported and sufficiently powered trials.
  • The Effect of Fava Bean (Vicia faba L.) Protein Ingestion on Myofibrillar Protein Synthesis at Rest and after Resistance Exercise in Healthy, Young Men and Women: A Randomised Control Trial

    Davies, Robert W.; Kozior, Marta; Lynch, Arthur E.; Bass, Joseph J.; Atherton, Philip J.; Smith, Ken; Jakeman, Philip M.; University of Chester (MDPI, 2022-09-06)
    The aim of the present study was to evaluate the effect of feeding fava bean (Vicia faba L.) protein (FBP) on resting and post-exercise myofibrillar fractional synthetic rate (myoFSR). In a parallel, double-blind, randomised control trial, sixteen young, healthy recreationally active adults (age = 25 (5) years, body mass = 70 (15) kg, stature = 1.72 (0.11) m, mean (SD)) ingested 0.33 g·kg−1 FBP (n = 8) or a negative control (CON, i.e., EAA-free mixture) (n = 8), immediately after a bout of unilateral knee-extensor resistance exercise. Plasma, saliva, and m. vastus lateralis muscle samples were obtained pre-ingestion and 3 h post-ingestion. MyoFSR was calculated via deuterium labelling of myofibrillar-bound alanine, measured by gas chromatography–pyrolysis–isotope ratio mass spectrometry (GC-Pyr-IRMS). Resistance exercise increased myoFSR (p = 0.012). However, ingestion of FBP did not evoke an increase in resting (FBP 29 [−5, 63] vs. CON 12 [−25, 49]%, p = 0.409, mean % change [95% CI]) or post-exercise (FBP 78 [33, 123]% vs. CON 58 [9, 107]%, p = 0.732) myoFSR. Ingestion of 0.33 g·kg−1 of FBP does not appear to enhance resting or post-exercise myoFSR in young, healthy, recreationally active adults.
  • Global prevalence of adaptive and prolonged infections’ muta-tions in the receptor-binding domain of the SARS-CoV-2 spike protein

    Lennerstrand, Johan; Palanisamy, Navaneethan; Uppsala University; University of Chester (MDPI, 2021-09-30)
    Several vaccines with varying efficacies have been developed and are currently administered globally to minimize the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite having an RNA-dependent RNA polymerase with a proofreading activity, new variants of SARS-CoV-2 are on the rise periodically. Some of the mutations in these variants, especially mutations on the spike protein, aids the virus in transmission, infectivity and host immune evasion. Further, these mutations also reduce the effectiveness of some of the current vaccines and monoclonal antibodies (mAbs). In the present study, using the available 984,769 SARS-CoV-2 nucleotide sequences on the NCBI database from the end of 2019 till 28 July 2021, we have estimated the global prevalence of so-called ‘adaptive mutations’ and ‘mutations identified in the prolonged infections’, in the receptor-binding domain (RBD) of the spike (S) protein. Irrespective of the geographical regions, in the case of the adaptive mutations, N501Y (48.38 %) was found to be the dominant mutation followed by L452R (17.52 %), T478K (14.31 %), E484K (4.69 %), S477N (3.29 %), K417T (1.64 %), N439K (0.7 %) and S494P (0.7 %). Other mutations were found to be less prevalent (less than 0.7 %). Since the last two months, there has been a massive increase of L452R and T478K mutations (delta variant) in certain areas. In the case of prolonged infections’ mutations (long-term SARS-CoV-2 infections), V483A (0.009 %) was found to be dominant followed by Q493R (0.009 %), while other mutations were found in less than 0.007 % of the studied sequences. The data obtained in this study will aid in the development of better infection control policies thereby curbing the spread of this virus.
  • SARS-CoV-2 variants of concern and Spike protein mutational dynamics in a Swedish cohort during 2021, studied by Nanopore sequencing

    Mannsverk, Steinar; Bergholm, Julia; Palanisamy, Navaneethan; Ellström, Patrik; Kaden, René; Lindh, Johan; Lennerstrand, Johan; Uppsala University; University of Chester (BMC, 2022-10-18)
    Background: Since the beginning of the COVID-19 pandemic, new variants of significance to public health have emerged. Consequently, early detection of new mutations and variants through whole-genome sequencing remains crucial to assist health officials in employing appropriate public health measures. Methods: We utilized the ARTIC Network SARS-CoV-2 tiled amplicon approach and Nanopore sequencing to sequence 4,674 COVID-19 positive patient samples from Uppsala County, Sweden, between week 15 and 52 in 2021. Using this data, we mapped the circulating variants of concern (VOC) in the county over time and analysed the Spike (S) protein mutational dynamics in the Delta variant throughout 2021. Results: The distribution of the SARS-CoV-2 VOC matched the national VOC distribution in Sweden, in 2021. In the S protein of the Delta variant, we detected mutations attributable to variants under monitoring and variants of interest (e.g., E484Q, Q613H, Q677H, A222V and Y145H) and future VOC (e.g., T95I and Y144 deletion, which are signature mutations in the Omicron variant). We also frequently detected some less well-described S protein mutations in our Delta sequences, that might play a role in shaping future emerging variants. These include A262S, Q675K, I850L, Q1201H, V1228L and M1237I. Lastly, we observed that some of the Delta variant’s signature mutations were underrepresented in our study due to artifacts of the used bioinformatics tools, approach and sequencing method. We therefore discuss some pitfalls and considerations when sequencing SARS-CoV-2 genomes. Conclusions: Our results suggest that genomic surveillance in a small, representative cohort can be used to make predictions about the circulating variants nationally. Moreover, we show that detection of transient mutations in currently circulating variants can give valuable clues to signature mutations of future VOC. Here we suggest six such mutations, that we detected frequently in the Delta variant during 2021. Lastly, we report multiple systematic errors that occurred when following the ARTIC Network SARS-CoV-2 tiled amplicon approach using the V3 primers and Nanopore sequencing, which led to the masking of some of the important signature mutations in the Delta sequences.
  • Screening for Mental Illness using GMHAT App of patients with Type 2 Diabetes Mellitus at a tertiary care hospital in India – A cross sectional study

    Majgi, Sumanth M.; Mal, Nihar M.; Krishna, Murali; Ebuenyi, Ikenna D.; Jones, Steven; Mysore Medical College and Research Institute; JSS Medical College, Mysore; University of Bangor; University College Dublin; University of Chester (Medknow Publications, 2022-10-31)
    People with diabetes will have some coexisting mental illness most of the time and its evaluation and management are essential for the well‑being of the person. With this background, the Global Mental Health Assessment Tool (GMHAT) app was used to screen for mental illness among type 2 diabetes mellitus patients in Mysore, India. Methods: A cross‑sectional study was conducted on 100 patients who were on treatment for type 2 diabetes for at least 6 months. Interviews were conducted using a structured GMHAT. Results: The mean age of the study participants was 48.8 ± 11.6 years. Among the 100 diabetic patients, 39% (n = 39) had mental illness and among the 39 subjects, 21% had depression, 14% had anxiety disorder and 4% suffered from organic disorder. Apart from diabetes, 29, 17, 13, 27, 23 and 20% had hypertension, chronic kidney disease, liver disease, retinopathy, neuropathy and nephropathy, respectively, as comorbid conditions. Conclusion: There is a higher prevalence of mental illness in patients with diabetes mellitus. The prevalence rate increases with an increase in the chronicity of diabetes. The use of the GMHAT app will help in rapid assessment and accurate diagnoses
  • Postnatal Protein Intake as a Determinant of Skeletal Muscle Structure and Function in Mice-A Pilot Study

    Giakoumaki, Ifigeneia; Pollock, Natalie; Aljuaid, Turki; Sannicandro, Anthony J.; Alameddine, Moussira; Owen, Euan; Myrtziou, Ioanna; Ozanne, Susan E.; Kanakis, Ioannis; Goljanek-Whysall, Katarzyna; et al. (MDPI, 2022-08-08)
    Sarcopenia is characterised by an age-related decrease in the number of muscle fibres and additional weakening of the remaining fibres, resulting in a reduction in muscle mass and function. Many studies associate poor maternal nutrition during gestation and/or lactation with altered skeletal muscle homeostasis in the offspring and the development of sarcopenia. The aim of this study was to determine whether the musculoskeletal physiology in offspring born to mouse dams fed a low-protein diet during pregnancy was altered and whether any physiological changes could be modulated by the nutritional protein content in early postnatal stages. Thy1-YFP female mice were fed ad libitum on either a normal (20%) or a low-protein (5%) diet. Newborn pups were cross-fostered to different lactating dams (maintained on a 20% or 5% diet) to generate three groups analysed at weaning (21 days): Normal-to-Normal (NN), Normal-to-Low (NL) and Low-to-Normal (LN). Further offspring were maintained ad libitum on the same diet as during lactation until 12 weeks of age, creating another three groups (NNN, NLL, LNN). Mice on a low protein diet postnatally (NL, NLL) exhibited a significant reduction in body and muscle weight persisting up to 12 weeks, unlike mice on a low protein diet only prenatally (LN, LNN). Muscle fibre size was reduced in mice from the NL but not LN group, showing recovery at 12 weeks of age. Muscle force was reduced in NLL mice, concomitant with changes in the NMJ site and changes in atrophy-related and myosin genes. In addition, μCT scans of mouse tibiae at 12 weeks of age revealed changes in bone mass and morphology, resulting in a higher bone mass in the NLL group than the control NNN group. Finally, changes in the expression of miR-133 in the muscle of NLL mice suggest a regulatory role for this microRNA in muscle development in response to postnatal diet changes. Overall, this data shows that a low maternal protein diet and early postnatal life low-protein intake in mice can impact skeletal muscle physiology and function in early life while postnatal low protein diet favours bone integrity in adulthood.
  • Small-RNA Sequencing Reveals Altered Skeletal Muscle microRNAs and snoRNAs Signatures in Weanling Male Offspring from Mouse Dams Fed a Low Protein Diet during Lactation

    Kanakis, Ioannis; Alameddine, Moussira; Folkes, Leighton; Moxon, Simon; Myrtziou, Ioanna; Ozanne, Susan E.; Peffers, Mandy J.; Goljanek-Whysall, Katarzyna; Vasilaki, Aphrodite; University of Liverpool; University of Chester; University of East Anglia; University of Cambridge; NUI Galway (MDPI, 2021-05-11)
    Maternal diet during gestation and lactation affects the development of skeletal muscles in offspring and determines muscle health in later life. In this paper, we describe the association between maternal low protein diet-induced changes in offspring skeletal muscle and the differential expression (DE) of small non-coding RNAs (sncRNAs). We used a mouse model of maternal protein restriction, where dams were fed either a normal (N, 20%) or a low protein (L, 8%) diet during gestation and newborns were cross-fostered to N or L lactating dams, resulting in the generation of NN, NL and LN offspring groups. Total body and tibialis anterior (TA) weights were decreased in weanling NL male offspring but were not different in the LN group, as compared to NN. However, histological evaluation of TA muscle revealed reduced muscle fibre size in both groups at weaning. Small RNA-sequencing demonstrated DE of multiple miRs, snoRNAs and snRNAs. Bioinformatic analyses of miRs-15a, -34a, -122 and -199a, in combination with known myomiRs, confirmed their implication in key muscle-specific biological processes. This is the first comprehensive report for the DE of sncRNAs in nutrition-associated programming of skeletal muscle development, highlighting the need for further research to unravel the detailed molecular mechanisms.
  • MicroRNAs as central regulators of adult myogenesis and proteostasis loss in skeletal muscle ageing

    Kanakis, Ioannis; Myrtziou, Ioanna; Goljanek-Whysall, Katarzyna; Vasilaki, Aphrodite; University of Liverpool; University of Chester; NUI Galway (CRC Press, 2021-11-23)
    Sarcopenia (from the Greek words sarca (σάρκα) = flesh and penia (πενία) = deficiency) is considered as an age-associated disease, characterized by dysregulation of the balance between muscle hypertrophy, atrophy and regeneration, which leads to advanced loss of skeletal muscle mass and function associated with a high risk of falls and fractures in the elderly. Numerous studies in humans and animals have explored the pathophysiology of musculoskeletal aging but the detailed mechanisms that contribute to skeletal muscle dysfunction have not been yet fully elucidated. Recently, several studies have focused on the role of microRNAs as a dynamic and promising epigenetic mechanism which may regulate post-transcriptional gene expression that modulate skeletal muscle homeostasis. In this chapter, we describe the crucial role of microRNAs in skeletal myogenesis during adulthood and their association with the pathogenesis of sarcopenia linked to proteostasis loss.

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