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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.
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Proteomic analysis and effects on osteogenic differentiation of exosomes from patients with ossification of the spinal ligamentLay Summary: Ossification of ligamentum flavum (OLF) is a hyperostotic spinal condition that compresses the spinal cord, leading to progressive motor and sensory dysfunction. Progression of ossification varies widely among individuals, making it important to identify factors that regulate disease activity. The study focused on exosomes, crucial for intercellular communication during disease development and progression. By comparing exosomes from patients with and without OLF, the study identified specific proteins that may play a role in spinal ligament ossification. These findings could help identify new markers to track disease progression and potential targets for treatment.
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Homocysteine levels and cardiovascular disease risk factors in chronic kidney disease (CKD), hypertensive and healthy Nigerian adults: A comparative retrospective studyOBJECTIVES: To investigate homocysteine (Hcy) levels in individuals with chronic kidney disease (CKD), hypertension and a healthy Nigerian population, and to assess their association with cardiovascular disease (CVD) risk. SETTING: The study was conducted using data from the Ibadan CRECKID (Cardiovascular and Renal Event in People with Chronic Kidney Disease) study in Nigeria. Participants: A total of 420 adults (aged 18+) categorised into three groups: individuals with stage 2 CKD or higher, hypertensive non-CKD individuals and normotensive individuals. OUTCOMES: The primary outcome was the difference in serum Hcy levels across the groups; secondary outcomes included the prevalence of hyperhomocysteinaemia (HHcy) and correlation with fibroblast growth factor (FGF). RESULTS: No significant difference in mean serum Hcy levels among the CKD, hypertensive and healthy groups (p=0.39) was observed. However, HHcy (≥15 µmol/L) prevalence was significantly higher in the hypertensive group (p<0.05). A strong positive correlation between Hcy levels and FGF was identified across all groups (p<0.001). CONCLUSIONS: The present study indicates that Hcy levels may not serve as a reliable predictor of CVD outcomes across populations with varying kidney function and CVD risk profiles.
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Risks to the clinician of risk management: Recalled and anticipated consequences of decision-makingBACKGROUND: Despite extensive literature studying how we make decisions in the face of uncertainty, the empirical study of real-world clinical decision-making in mental health practice remains limited. Decisions in clinical settings are not just made on the basis of clinical factors. A key non-clinical influence on decision making is the clinician’s concerns about the ‘threat’ to themselves from a future adverse incident and the subsequent retrospective scrutiny of their decision-making. A better understanding of non-clinical processes is essential to inform better ways of guiding effective decision-making. More specifically, delineating the nature of this ‘threat’ process will also inform approaches to patient safety. AIMS: The objective of the current study was to delineate consequences recalled and anticipated by mental health clinicians making decisions under uncertainty. METHODS: This was an analysis of data arising from six focus group discussions with professionals involved in decisions to admit patients to psychiatric hospitals (consultant psychiatrists, approved mental health practitioners, crisis resolution home treatment teams, and liaison psychiatry practitioners) in one National Health Service Trust, UK. The data were thematically analyzed to identify the nature of ‘threat’ processes that arise in clinical decision-making. RESULTS: Themes identified included (i) the location of the effect of the anticipated/recalled consequence(s), (ii) the location of the origin of the consequence, and (iii) the nature of the consequence. The recalled and anticipated consequences of decision-making were overwhelmingly, but not exclusively, negative. The consequences were largely perceived to be directed towards the self (i.e., the clinician) and were considered to originate from external scrutiny by peers, organizational leadership, and the patient safety system/processes. CONCLUSIONS: The process of making decisions to admit patients to hospital consistently involved the decision-maker’s concern with the future consequences for them, either from a prior or future adverse event. The findings of this study, alongside other evidence of the complexity of decision-making, have implications for improving and studying clinical decision-making (and, by extension, patient care and outcomes), patient safety responses, and professional well-being.
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Implantable loop recorder migration: Case-based review and implications for clinical practiceImplantable loop recorders (ILRs) are vital for continuous rhythm monitoring; however, post-implantation migration can impair device function. ILR migration may range from minor positional shifts causing discomfort to severe displacement, potentially resulting in device malfunction or requiring surgical intervention. This review examines migration patterns to identify factors associated with ILR migration. A systematic literature search was conducted in PubMed, Cochrane Library, CINAHL, and EMBASE for case reports on ILR migration from inception to October 2024. Data on patient demographics, comorbidities, device models, implantation sites, detection times, and interventions were qualitatively synthesised to identify factors linked to migration. Older age, female gender, and specific comorbidities emerged as migration risk factors. Device implantation angulation and depth were common contributors. Migration typically followed a posterior or inferior direction and was detected within 5-35 days, often presenting as loss of connection or continuous chest pain. Migration was also observed following patient manipulation of the device. Although migration is rare, cases requiring video-assisted thoracoscopic surgery (VATS) highlight the significant morbidity associated with this complication. Optimising implantation techniques and employing effective follow-up strategies can reduce the risk of migration and improve migration detection. Further studies with standardised reporting are needed to better understand this complication. [Abstract copyright: Crown Copyright © 2025 Published by Elsevier Inc.]
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Leading evidence-based practice: nurse managers’ strategies for knowledge utilisation in acute care settingsBACKGROUND: The implementation of evidence-based practice (EBP) in nursing is essential for improving patient care outcomes, yet systemic barriers, leadership challenges, and resource limitations continue to hinder its integration into clinical practice. Nurse managers (NMs) play a crucial role in bridging the gap between policy directives and frontline implementation, yet the dynamic interplay between leadership strategies, knowledge utilisation, and organisational barriers remains underexplored, particularly in resource-constrained settings. This study examines how NMs navigate these challenges to sustain EBP adoption in acute care environments. METHODS: This collective case study employed a longitudinal qualitative design across two acute care settings in the UK. Data were collected over eight months through semi-structured interviews with NMs, nonparticipant observations, and document analysis of clinical guidelines and internal reports. A thematic analysis approach was used to synthesise findings and provide a nuanced understanding of leadership strategies and systemic factors influencing EBP adoption. FINDINGS: Six interconnected themes emerged: (1) Adaptive leadership strategies, where NMs employ a hybrid of directive and collaborative leadership approaches to drive EBP; (2) Overcoming organisational and resource barriers, including staff shortages, financial constraints, and competing priorities; (3) Knowledge utilisation and learning networks, highlighting the role of informal mentorship, structured CPD, and peer learning in sustaining EBP; (4) Digital transformation and EBP, examining the benefits and challenges of integrating digital tools and addressing IT literacy gaps; (5) Patient-centred adaptations, exploring how NMs balance evidence-based interventions with patient preferences and cultural considerations; and (6) Emotional and psychological support, underscoring the importance of managing staff resistance and mitigating change fatigue. CONCLUSION: Findings of this study emphasise the pivotal role of NMs in driving EBP implementation through adaptive leadership, strategic resource management, and fostering learning networks. Addressing organisational barriers requires multi-level interventions that integrate leadership actions with systemic enablers to promote sustainable, evidence-informed nursing practice. Findings provide critical insights for healthcare policymakers, hospital administrators, and educators in enhancing EBP uptake within resource-limited settings.
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FTO rs17817449 variant increases the risk of severe obesity in a Brazilian cohort: A case-control studyPURPOSE: Obesity is a complex disease caused by a combination of genetic, environmental, and epigenetic factors, and is associated with an increased risk of chronic diseases. The leptin-melanocortin pathway integrates peripheral signals about the body's energy stores with a central neuronal circuit in the hypothalamus. This pathway has been extensively studied over the years, as genetic variations in genes related to it may play a crucial role in determining an individual's susceptibility to obesity. Therefore, we analyzed the association between obesity and specific polymorphisms in leptin-melanocortin-related genes such as LEPR rs1137101, POMC rs1042571, LEP rs7799039, BDNF rs6265, FTO rs17817449, CART rs121909065, and NPY rs16147/rs5574. PATIENTS AND METHODS: The study enrolled 501 participants from Rio de Janeiro, Brazil, with obesity class II or greater (BMI ≥ 35 kg/m2) and normal weight controls (18.5≤ BMI ≤24.9 kg/m2). We collected demographic, body composition, biochemical, and genotyping data by real-time PCR, and performed logistic and linear regression analyses to investigate the association of polymorphisms with severe obesity status and obesity-related quantitative parameters. RESULTS: Individuals with severe obesity had significantly higher anthropometric measures, blood pressure, and biochemical levels. The FTO rs17817449 TT genotype was associated with a significantly higher risk of developing severe obesity, and distinct cytokine expression was observed across the FTO rs17817449 genotypes. The BDNF rs6265 dominant-model and NPY rs16147 CC genotypes were associated with triglyceride levels and childhood obesity, respectively. Finally, individuals with obesity were more likely to carry a greater number of risk alleles than those without obesity. CONCLUSION: Our study observed an important association between FTO rs17817449 polymorphism with obesity and obesity-related traits. Additionally, BDNF rs6265 dominant-model was associated with triglyceride serum levels, and NPY rs16147 may have a role in obesity onset.
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Anti-inflammatory effects of Phyllanthus amarus extracts against Benzene-induced Leukemia in ratsBACKGROUND: The present study examined the protective effects of extracts from Phyllanthus amarus on benzene-induced leukemia in Wistar rats. Benzene is a carcinogen linked to increased leukemia risk. OBJECTIVES: The study aimed to assess the impact of P. amarus extracts, prepared via different drying methods, on immunological, biochemical, and histopathological parameters. METHODS: Aqueous, methanolic, and ethanolic extracts were prepared from P. amarus using room drying, oven drying, and sun drying. The rats were treated with benzene and the extracts. For the immunological parameters, C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and IL-10 were measured using the enzyme-linked immunosorbent assay. For biochemical parameters, microalbumin, urea, creatinine, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) were assessed using spectrophotometry. At the same time, for histopathological examination, liver and bone marrow tissues were stained using hematoxylin and eosin and analyzed for morphological changes. RESULTS: Research findings showed no significant difference in CRP among the groups (P=0.197), indicating no significant inflammation or tissue damage. TGF-β levels were significantly lower in treatment groups compared to the positive control group (P=0.015), suggesting anti-inflammatory or immunosuppressive effects. No significant differences were found in IL-8, TNF-α, and IL-10 levels. The aqueous extract prepared by room drying significantly decreased microalbumin levels (P=0.016), representing potential protective effects on kidney function. The methanolic extract prepared by sun drying significantly reduced creatinine (P=0.032) and ALT (P=0.048) levels, implying beneficial effects on liver function. Histopathological examinations revealed that the extracts modulated bone marrow and liver morphologies, reducing inflammation while improving cellularity and morphology. CONCLUSION: P. amarus extracts demonstrated potential anti-inflammatory effects in benzene-induced leukemia by significantly reducing TGF-β levels without inducing inflammation, as evidenced by stable CRP, IL-8, and TNF-α levels. These findings suggest that the extracts may help mitigate inflammation associated with benzene exposure, highlighting their potential as adjunctive therapies in leukemia treatment. More studies are needed to understand these protective processes completely and investigate their clinical uses.
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A standardised comparison of chest and percutaneous drainage catheters to evaluate the applicability of the ‘French’ sizing unitsA variety of medical specialities undertake percutaneous drainage but understanding of device performance outside radiology is often limited. Furthermore, the current catheter sizing using the “French” measurement of outer diameter is unhelpful; it does not reflect the internal diameter and gives no information on flow rate. To illustrate this and to improve catheter selection, notably for chest drainage, we assessed the variation of drain performance under standardised conditions. Internal diameter and flow rates of 6Fr.-12Fr. drainage catheters from 8 manufacturers were tested to ISO 10555-1 standard: Internal diameters were measured with Meyer calibrated pin-gauges. Flow rates were calculated over a period of 30s after achieving steady state. Evaluation demonstrated a wide range of internal diameters for the 6Fr., 8Fr., 10Fr. and 12Fr. catheters. Mean measurements were 1.49 mm (SD:0.07), 1.90 mm (SD:0.10), 2.43 mm (SD:0.11) and 2.64 mm (SD:0.03) respectively. Mean flow rates were 128 mL/min (SD:37.6), 207 mL/min (SD: 55.1), 291 mL/min (SD:36.7) and 303 mL/min (SD:20.2) respectively. There was such variance that there was overlap between catheters of different size: thin-walled 10Fr. drains performed better than 12Fr. “Seldinger” chest drains. Better understanding of drain characteristics and better declaration of performance data by manufacturers are required to allow optimum drain choice for individual patients and optimum outcomes.
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Early years practitioners' and public health consultants' perspectives on the use of interactive electronic devices in young children: A qualitative studyBackground: Interactive electronic devices (IEDs) are ubiquitous in young children's lives. However, research on their impact on learning and development is still limited. The aim of this study was to understand the perspectives of early years practitioners (EYPs) and public health consultants (PHCs) on the use of IEDs in children aged 3–5. Methods: Using purposive sampling techniques, we recruited four EYPs and two PHCs from children's nurseries and a government organisation in the northwest of England. Semi‐structured interviews were used to collect data, which were audio‐recorded, transcribed verbatim and anonymised. Data were analysed using reflective thematic analysis. Results: EYPs and PHCs noted that although IEDs could negatively impact child development and behaviour, they could also aid in learning. EYPs expressed concerns about the impact of parents' own IED habits on children's communication and social skills. On the other hand, PHCs stressed that substituting outdoor play with the use of these devices could affect children's social and physical skills and reduce physical activity levels, which are crucial for development. Finally, both EYPs and PHCs agreed that there was a need to improve parents' and EYP's knowledge and to develop interactive interventions to promote an understanding of how IEDs should be used with young children. Conclusion: EYPs and PHCs acknowledge the potential advantages of using IEDs as a teaching tool for children. However, they have concerns about the long‐term effects on communication, social and physical skills and how children are impacted by their parents' use of these devices. To support policy statements, future research should offer further evidence of the benefits and harms of IED use.
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Essential information about nanotechnology in cardiologyCardiology, as a medical specialty, addresses cardiovascular diseases (CVDs), a leading cause of global mortality. Nanomaterials offer transformative potential across key areas such as drug delivery, stem cell therapy, imaging, and gene delivery. Nanomaterials improve solubility, bioavailability, and targeted delivery in drug delivery, reducing systemic side effects. Examples include gas microbubbles, liposomal preparations, and paramagnetic nanoparticles, which show promise in treating atherosclerosis. Stem cell therapy benefits from nanotechnology through enhanced cell culture conditions and three-dimensional scaffolds that support cardiomyocyte growth and survival. Gold nanoparticles and PLGA-derived microparticles further improve stem cell viability. In imaging, nanomaterials enable advanced visualization techniques such as magnetic resonance imaging (MRI) with direct labeling and optical tracking via dye-conjugated nanoparticles. In gene delivery, polymeric nanocarriers like polyethyleneimine, dendrimers, and graphene-based materials offer efficient, non-viral alternatives, with magnetic nanoparticles showing promise in targeted applications. Ongoing research highlights the potential of nanomaterials to revolutionize CVD management by improving therapeutic outcomes and enabling precision medicine. These advancements position nanotechnology as a cornerstone of modern cardiology.
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In vitro erythropoiesis: The emerging potential of induced pluripotent stem cells (iPSCs)Due to global blood shortages and restricted donor blood storage, the focus has switched to the in vitro synthesis of red blood cells (RBCs) from induced pluripotent stem cells (iPSCs) as a potential solution. Many processes are required to synthesize RBCs from iPSCs, including the production of iPSCs from human or animal cells, differentiation of iPSCs into hematopoietic stem cells, culturing, and maturation of the hematopoietic stem cells (HSC) to make functional erythrocytes. Previous investigations on the in vitro production of erythrocytes have shown conflicting results. Some studies have demonstrated substantial yields of functional erythrocytes, whereas others have observed low yields of enucleated cells. Before large-scale in vitro RBC production can be achieved, several challenges which have limited its application in the clinic must be overcome. These issues include optimizing differentiation techniques to manufacture vast amounts of functional RBCs, upscaling the manufacturing process, cost-effectiveness, and assuring the production of RBCs with good manufacturing practices (GMP) before they can be used for therapeutic purposes.
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Brief observation of symptoms of autism (BOSA): an alternative or replacement to autism diagnostic observation schedule (ADOS)The COVID-19 pandemic has led to significant changes in many areas of healthcare, such as a shift to telehealth models. This has created challenges for families with children awaiting autistic spectrum disorder evaluations. The Brief Observation of Symptoms of Autism (BOSA) was developed as a novel method to ensure that service users referred to services could still take part in structured observations during autism assessments in the pandemic. A service user was offered a BOSA when a clinician could not administer the Autism Diagnostic Observation Schedule–Second Edition (ADOS-2) due to COVID-19 precautions. The designers of the ADOS-2 felt that it was not designed to be used for video assessments and that its sensitivity would be significantly affected in face-to-face assessments with face covers. This paper aims to highlight some advantages and disadvantages of BOSA. Four cases were studied in a BOSA clinic, half of whom met the threshold of autism spectrum disorder based on scoring of ADOS-2 after BOSA assessment. It was found that BOSA, just like ADOS-2, allows health professionals to observe indicators of autism reliably while maintaining social distance. It is a time-efficient measure, as unlike ADOS-2, which takes about 45 minutes to be administered, it takes much less time (around 15 minutes). While the sample size is low, the issues identified may be taken forward in future studies.
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Maternal obesity and metabolic (dysfunction) associated fatty liver disease in pregnancy: a comprehensive narrative reviewIntroduction: Obesity and metabolic-associated fatty liver disease (MAFLD) during pregnancy constitute significant problems for routine antenatal care, with increasing prevalence globally. Similar to obesity, MAFLD is associated with a higher risk for maternal complications (e.g. pre-eclampsia and gestational diabetes) and long-term adverse health outcomes for the offspring. However, MAFLD during pregnancy is often under-recognized, with limited management/treatment options. Areas covered: PubMed/MEDLINE, EMBASE, and Scopus were searched based on a search strategy for obesity and/or MAFLD in pregnancy to identify relevant papers up to 2024. This review summarizes the pertinent evidence on the relationship between maternal obesity and MAFLD during pregnancy. Key mechanisms implicated in the underlying pathophysiology linking obesity and MAFLD during pregnancy (e.g. insulin resistance and dysregulated adipokine secretion) are highlighted. Moreover, a diagnostic approach for MAFLD diagnosis during pregnancy and its complications are presented. Finally, promising relevant areas for future research are covered. Expert opinion: Research progress regarding maternal obesity, MAFLD, and their impact on maternal and fetal/offspring health is expected to improve the relevant diagnostic methods and lead to novel treatments. Thus, routine practice could apply more personalized management strategies, incorporating individualized algorithms with genetic and/or multi-biomarker profiling to guide prevention, early diagnosis, and treatment.
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Advances in preparation of acellular human dermis for tissue banking and transplantationNon-healing wounds cost the National Health Service over £5.6 billion annually in wound management. Skin allografts are used to treat non-healing wounds, ulcers and burns, offering the best protection against infection. In order to allow host cells to repopulate and to avoid immunogenicity, cell components are removed through decellularisation. Decellularisation of human dermis has so far been performed in NHS Blood and Transplant using a combination of two enzymes (RNase T1 and the recombinant human DNase Pulmozyme)®. This study aims at validating a new method to remove DNA from donated dermis via the use of a single enzyme, Benzonase, known for its effectiveness of DNA digestion. Skin samples were decellularised by removing the epidermis, lysing of dermal cells, removal of cellular fragments by a detergent wash and removal of nucleic acids by a nuclease incubation with either Benzonase or Pulmozyme + RNase T1. DNA quantification with PicoGreen, as well as histology on wax-embedded biopsies, stained with DAPI and haemotoxylin and eosin, were performed. In vitro toxicity test on human osteosarcoma immortalised cells and skin fibroblasts, and biomechanical (tensile) testing, were also performed. The effectiveness of DNA digestion with the new methodology was comparable to previous procedure. Mean DNA removal percentage following decellularisation with Pulmozyme + RNase was 99.9% (3.83 ng/mg). Mean DNA removal percentage with Benzonase was 99.8% (9.97 ng/mg). Histology staining showed complete decellularisation following either method. Benzonase was proven to be non-toxic to both cell lines used, and a one-way Anova test showed no significant difference in neither stress nor strain between acellular dermal matrix decellularised with either Benzonase or Pulmozyme + RNase T1. Benzonase was able to effectively decellularise dermis after prior removal of epidermis. It performed just as well as the combination of Pulmozyme + RNase T1, but represents significant advantages in terms of cost effectiveness, procurement and storage; Benzonase has been successfully used in the decellularisation of other tissues, thus would be better for Tissue Banking use. Switching to this combined DNase/RNase can have far-reaching consequences in the production of acellular human dermal matrix by NHSBT and in the treatment of patients requiring it.
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Navigating food fraud: A survey of Nigerian consumer knowledge and attitudesFood fraud presents a growing threat globally, impacting consumer health; food safety; and brand credibility. The key motivation for food fraud is usually an economic or financial advantage. Economically motivated food fraud (EMA) is the illegal deception, deliberate and intentional substitution or addition of a substance in a food product, which may pose a possible health risk to unsuspecting consumers. This study aims to assess the awareness and attitudes of Nigerian consumers towards food authenticity and the regulatory measures in place to combat food adulteration. The study comprised 2160 respondents who were asked about their knowledge of high-profile food fraud incidents, frequently adulterated products, and their opinions of the effects of food fraud and preventative measures. The findings of this study revealed that more than a third of respondents were unfamiliar with the term “food fraud”. However, they were aware of local high-profile cases, such as “plastic rice” and counterfeit dairy products. Most participants relied on point-of-sale information for assessing food authenticity, with street vendors being viewed as potential sources of food adulteration. The study also found that more than half of the respondents were concerned about food fraud regardless of whether it involved local or imported products. A wide variety of food items were identified as prone to adulteration or fraudulent activity. These included alcoholic drinks, dairy products, honey, rice, and tomato paste, amongst others. These findings highlight the need for improved consumer awareness, regulatory effectiveness, and remediation efforts to combat food fraud in Nigeria.
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Legal Implications for Clinicians in Cybersecurity Incidents: A ReviewCybersecurity incidents in healthcare present significant legal implications for clinicians, necessitating careful consideration of technological advancements and regulatory frameworks. This literature examines the healthcare cybersecurity landscape, emphasizing clinicians’ challenges, and legal responsibilities. It explores the impact of advanced technologies such as artificial intelligence and quantum computing, highlighting the potential benefits and risks, including biases and ethical dilemmas. The review addresses international regulatory differences, offering a comparative analysis of how various countries handle cybersecurity incidents. This analysis provides insights into best practices and identifies areas for improvement. Practical recommendations are provided, tailored to different healthcare settings, including large hospitals and small clinics, to enhance cybersecurity preparedness. Case studies illustrate real-world scenarios, offering practical guidance for clinicians in managing cybersecurity challenges. The review also identifies critical gaps in the literature, particularly concerning artificial intelligence ethics and international regulatory frameworks, suggesting specific areas for future research. These findings underscore the need for robust cybersecurity policies, comprehensive training for healthcare professionals, and a nuanced understanding of the legal landscape. This review informs policymakers, clinicians, and researchers about the evolving nature of cybersecurity challenges in healthcare, addressing key concerns raised by reviewers and contributing to a comprehensive understanding of the field.
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Mediating kinase activity in Ras-mutant cancer: Potential for an individualised approach?It is widely acknowledged that there is a considerable number of oncogenic mutations within the Ras superfamily of small GTPases which are the driving force behind a multitude of cancers. Ras proteins mediate a plethora of kinase pathways, including the MAPK, PI3K, and Ral pathways. Since Ras was considered undruggable until recently, pharmacological targeting of pathways downstream of Ras has been attempted to varying success, though drug resistance has often proven an issue. Nuances between kinase pathway activation in the presence of various Ras mutants are thought to contribute to the resistance, however, the reasoning behind activation of different pathways in different Ras mutational contexts is yet to be fully elucidated. Indeed, such disparities often depend on cancer type and disease progression. However, we are in a revolutionary age of Ras mutant targeted therapy, with direct-targeting KRAS-G12C inhibitors revolutionising the field and achieving FDA-approval in recent years. However, these are only beneficial in a subset of patients. Approximately 90% of Ras-mutant cancers are not KRAS-G12C mutant, and therefore raises the question as to whether other distinct amino acid substitutions within Ras may one day be targetable in a similar manner, and indeed whether better understanding of the downstream pathways these various mutants activate could further improve therapy. Here, we discuss the favouring of kinase pathways across an array of Ras-mutant oncogenic contexts and assess recent advances in pharmacological targeting of various Ras mutants. Ultimately, we will examine the utility of individualised pharmacological approaches to Ras-mediated cancer.
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Mental health and public health: Improving mental health and well-being of communities in the modern world: A pragmatic approach using the Global Mental Health Assessment Tool/PCThe World Health Organization report of 2022 on mental health highlights the slow progress in reducing the treatment gap for people with mental illness worldwide. It emphasizes that everyone should participate in improving the mental health and well-being of the communities. The governments should put their act together and all agencies should work in coordination to address the mental health needs of their population. They should also focus on mental health promotion, early intervention, and prevention of suicide. The Mental Health Action Plan 2013–2030 outlines the importance of leadership and governance for mental health in providing comprehensive, integrated, and responsive mental health and social care services in community-based settings. Stigma, human resource shortages, fragmented service delivery models, and poor commitment of authorities for mental health are some of the factors for the ongoing service gap in mental health. Providing mental health knowledge and assessment skills to frontline workers, supporting frontline workers by mental health specialists using their leadership skills, and fully utilizing mobile and Internet technology in providing education and training as well as providing services could bring down the treatment gap of mental disorders worldwide. The Global Mental Health Assessment Tool for Primary Care and General Health Setting (GMHAT/PC)-based training package has been developed and successfully implemented in training frontline health workers in different parts of the word. The authors propose that this may be a pragmatic way to integrate mental health in public health by skilling frontline workers in assessing mental health along with physical health and by providing holistic care.
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Co-presence of Epstein-Barr Virus and Human Papillomavirus is associated with a high frequency of p53 gene mutation in cervical cancer diagnosed in southern NigeriaBackground: Evidence shows that the co-existence of Human papillomavirus (HPV) and Epstein-Barr virus (EBV) is associated with aggressive and poorly differentiated cervical squamous cell carcinomas (CSCC) phenotype. Aim: This study aimed to determine the frequency of mutant p53 (mtp53) gene in single and co-existence of HPV and oncogenic EBV latent membrane protein 1 (E-LMP1) among women diagnosed with CSCC in Southern Nigeria. Methods: This retrospective cohort study included 105 cervical cancer tissues, diagnosed between January 2016 and December 2018. The tissue sections were immunohistochemically stained for mtp53, E-LMP1, and HPV proteins and scored accordingly. Descriptive, Chi- square test and Pearson’s correlation were performed, and statistical significance was set at p≤0.05. Result: Among the stained sections, the frequency of HPV, E-LMP1, and E-LMP1/HPV detection was 8.6%, 20.0%, and 42.9%, respectively. The mtp53 detection was higher in ELMP1/HPV co-presence (86.7%) compared with HPV and ELMP1 mono-presence (55.6%, and 14.3%, respectively), and this was statistically significant (p< 0.0001). The prevalence of invasive and non-invasive cases of CSCC were 62.9% and 37.1%, respectively. E-LMP1 and HPV co-presence were significantly higher in invasive cervical cancer (48.5%) compared to non-invasive cervical cancer cases (33.3%) at p= 0.156. The E-LMP1 presence was significantly higher in poorly differentiated CSCC (50.0%) compared to the moderately and well- differentiated CSCC (25.0% and 10.5%, respectively) at p= 0.011. Conclusion: This study revealed a higher frequency of EBV/HPV co- infection in CSCC. It also shown- that a higher frequency of mtp53 in E-LMP1 and HPV co-presence, suggesting that E-LMP1 could be responsible for the high CSCC lethality in West Africa.
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Lifelong dietary protein restriction induces denervation and skeletal muscle atrophy in miceAs a widespread global issue, protein deficiency hinders development and optimal growth in offspring. Maternal low-protein diet influences the development of age-related diseases, including sarcopenia, by altering the epigenome and organ structure through potential increase in oxidative stress. However, the long-term effects of lactational protein restriction or postnatal lifelong protein restriction on the neuromuscular system have yet to be elucidated. Our results demonstrated that feeding a normal protein diet after lactational protein restriction did not have significant impacts on the neuromuscular system in later life. In contrast, a lifelong low-protein diet induced a denervation phenotype and led to demyelination in the sciatic nerve, along with an increase in the number of centralised nuclei and in the gene expression of atrogenes at 18 months of age, indicating an induced skeletal muscle atrophy. These changes were accompanied by an increase in proteasome activity in skeletal muscle, with no significant alterations in oxidative stress or mitochondrial dynamics markers in skeletal muscle later in life. Thus, lifelong protein restriction may induce skeletal muscle atrophy through changes in peripheral nerves and neuromuscular junctions, potentially contributing to the early onset or exaggeration of sarcopenia.
