Chester Medical School
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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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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Identification of Candidate Synovial Fluid Biomarkers for the Prediction of Patient Outcome After Microfracture or OsteotomyBackground: Biomarkers are needed to predict clinical outcomes for microfracture and osteotomy surgeries to ensure patients can be better stratified to receive the most appropriate treatment. Purpose: To identify novel biomarker candidates and to investigate the potential of a panel of protein biomarkers for the prediction of clinical outcome after treatment with microfracture or osteotomy. Study Design: Descriptive laboratory study. Methods: To identify novel candidate biomarker proteins, we used label-free quantitation after liquid chromatography–tandem mass spectrometry of dynamic range-compressed synovial fluids (SFs) from individuals who responded excellently or poorly (based on change in Lysholm score) to microfracture (n = 6) or osteotomy (n = 7). Biomarkers that were identified in this proteomic analysis or that relate to osteoarthritis (OA) severity or have predictive value in another early OA therapy (autologous cell implantation) were measured in the SF of 19 and 13 patients before microfracture or osteotomy, respectively, using commercial immunoassays, and were normalized to urea. These were aggrecanase-1 (ADAMTS-4), cartilage oligomeric matrix protein (COMP), hyaluronan (HA), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), matrix metalloproteinase 1 and 3, soluble CD14, S100 calcium binding protein A13, and 14-3-3 protein theta (YWHAQ). Levels of COMP and HA were also measured in the plasma of these patients. To find predictors of postoperative function, multivariable regression analyses were performed. Results: Proteomic analyses highlighted YWHAQ and LYVE-1 as being differentially abundant between the clinical responders/improvers and nonresponders after microfracture. A linear regression model after backward variable selection could relate preoperative concentrations of SF proteins (HA, YWHAQ, LYVE-1), activity of ADAMTS-4, and patient demographic characteristics (smoker status and sex) with Lysholm score 12 months after microfracture. Further, a generalized linear model with elastic net penalization indicated that lower preoperative activity of ADAMTS-4 in SF, being a nonsmoker, and being younger at the time of operation were indicative of a higher postoperative Lysholm score (improved joint function) after osteotomy surgery. Conclusion: We have identified biomarkers and generated regression models with the potential to predict clinical outcome in patients treated with microfracture or osteotomy of the knee.
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iCan, Empowering Recovery: Evaluating a Patient-Centred Cancer Rehabilitation Programme across the Cancer Care ContinuumBackground/Objectives: The adverse effects of cancer and the long-term sequelae of associated treatments result in reduced quality of life and increased mortality for patients. Supporting patients with cancer to mitigate adverse outcomes is an important aspect of oncology care and the primary purpose of cancer rehabilitation. A retrospective service evaluation was conducted to evaluate the effectiveness of the core iCan patient-centred cancer rehabilitation service. Methods: At the beginning and end of a five-week programme, a series of questionnaires evaluating changes in mental health and wellbeing, and physical activity performance/attitudes, and functional capacity were administered to participants. Results: Following iCan, we found that functional capacity was improved (30 s sit-to-stand: +6.3 repetition; d = −1.00, p < 0.001) and that self-reported physical activity was increased (~1173 MET-mins/wk; d = −0.76, p < 0.001); participants also perceived greater capability, opportunity, and motivation to be active. Mental wellbeing was also improved (SWEMWBS: d = −0.69, p < 0.001), whilst fatigue was reduced (FACIT: d = −0.77, p < 0.001). Conclusion: It appears that iCan has beneficial effects upon the physical/functional and psychological health of its participants. Where data are available, there appear to be clinically significant improvements across the range of measured functional, wellbeing, and activity/sedentariness outcomes, which suggest that participation in iCan is instrumental in adding value to the health and wellbeing of patients.
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Redox, Cysteines, and Kinases - A Triad Sustaining Myeloid LeukemiaReactive oxygen species (ROS) work as a second messenger, modulating cell response and establishing homeostasis. Abrupt changes in ROS are used to modulate transient cell response to different stimuli, from viral infection to inflammation. Chronic exposure to high ROS concentration can cause cellular damage and promote the development of diseases. Leukemogenesis is adapted to high concentrations of ROS, hijacking the ROS system, and uses kinase cascades to promote survival advantages. The oxidation-reduction (redox) machinery is composed of enzymes that orchestrate all classes of protein and use available Cys as transmitters and sensors, to disseminate stress signals through cells via kinase cascades. Myeloid leukemias (MLs) are known for being a heterogeneous disease, and clonal diversity is remarkably characterized by differences in the activation of kinase-regulated signaling cascades to provide survival advantage. Stress-activated kinase cascades and other cascades are regulated by the ROS system. Several studies present nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) and the ER-resident NOX4 as key elements of ROS activity in healthy myeloid cells and myeloid leukemia. Targeting ROS presents an attractive therapeutic strategy for (MLs) patients, but the boundaries between pro-apoptotic and anti-apoptotic ROS concentrations are not well established. Detailed understanding of the signaling switches that determine cell fate needs to be well understood. This work explores several aspects of the redox system and thiol-mediated reactions with focus on kinase signaling in myeloid cancers and highlights some of the challenges.
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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.
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Active case finding and evaluation of IL-6 production among household contacts of pulmonary tuberculosis patients in a high disease settingBackground: Tuberculosis (TB) is a top infectious disease killer worldwide and remains a huge public health concern. However, most TB case findings are limited to self-referral (passive case finding), when individuals develop symptoms of TB. Only 15% of disease burden in Nigeria are reported. In view of this, it is important to assess the latent and active disease burden amongst HHC of TB patients suffering from pulmonary TB. In addition, it has been suggested that IL-6 levels could be used as a prognostic marker in exposed individuals. IL-6 levels were assessed in this cohort. Methods: A total of 205 subjects participated in this study, comprising 62 pulmonary TB index cases and 143 of their household contacts. Also, 54 apparently healthy subjects were recruited to serve as controls. Active case finding was performed amongst the HHC, using sputum and blood samples; they were tested for active TB. Blood samples were also collected for measuring IL-6 levels. Results: Findings reveal 6.3% previously undiagnosed active TB among the HHC of the TB patients and a significantly higher number of latently infected TB cases compared to the control population (p=0.0078). There were significant differences when comparing HIV co-infected index group to their HIV negative counterparts (P=0.032). Significantly different IL-6 levels were found among the study groups and sub-groups (p<0.0001), with significantly higher levels in TB mono-infection compared to in TB/HIV co-infection (p=0.031).Conclusions: These results demonstrate the importance of active TB case finding for TB control and the possible role of IL-6 as a diagnostic marker in TB control.
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Assessment of the Demographic Burden of Epidemics and Diseases within the African Sub-Region: A Review of Recent Epidemiological Data, Responses, and Resultant Psychosocial Risk TendenciesBackground: Over the past few decades, epidemic outbreaks and disease occurrences have become more frequent and widespread in Africa, posing challenges for poor countries in the region and impacting vulnerable populations. Limited resources, inadequate healthcare infrastructure, socioeconomic inequalities, malnutrition, mass gatherings, and lack of proper sanitation and hygiene contribute to Africa’s high burden of epidemics and infectious diseases such as cholera, measles, monkeypox, Ebola viral disease, and COVID-19. This paper reviewed epidemic outbreaks and diseases transmitted through intimate contact in Africa and their impacts on vulnerable populations. Methods: A narrative review approach was adopted to gather and analyze the relevant literature on epidemic outbreaks in African sub-regions. The review encompassed causes, transmission patterns, demographic impact, community susceptibility, preventive measures, and psychosocial risk-taking behaviors. Results: This study emphasizes the importance of addressing the causes of response lapses and the resulting human, material, and economic losses in the region. Effective preventive measures include disease surveillance, early mitigation strategies, contact tracing, personal protective measures, improved political and public health leadership, and socioeconomic equity. However, the review highlights challenges in implementing these measures effectively due to limited resources, delayed detection, and difficulties in scaling up response solutions. Conclusions: There is a need for a comprehensive approach involving health departments, infrastructure development, and addressing socioeconomic factors.
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Phytochemical Composition, In Silico Molecular Docking Analysis and Antibacterial Activity of Lawsonia inermis Linn Leaves Extracts against Extended Spectrum Beta-Lactamases-Producing Strains of Klebsiella pneumoniaeKlebsiella pneumoniae is an opportunistic Gram-negative bacterium in the Enterobacteriaceae family associated with a wide range of diseases, such as pneumonia, bloodstream infections, meningitis and urinary tract infections. Infections caused by drug-resistant strains of Klebsiella pneumoniae pose a significant threat to the effectiveness of conventional antibiotics. Hence, this has led to the need to explore alternative antimicrobial therapies, especially natural products derived from plant sources. This study assessed the phytochemical composition and antibacterial properties and performed a molecular docking analysis of Henna leaves (Lawsonia inermis L.) extracts on strains of Klebsiella pneumoniae. Crude ethanol and methanol extracts of L. inermis L. were prepared at different concentrations (25, 50, 75 and 100 mg/mL) and tested on extended spectrum beta-lactamases (ESBLs)-producing strains of Klebsiella pneumoniae. Phytocompounds were identified using gas chromatography–mass spectrometry (GC-MS) and further subjected to virtual ligands screening with DataWarrior (v05.02.01) and a molecular docking analysis using AutoDock4.2 (v4.2.6). The active compounds of L. inermis L. were determined by the docking analysis, including phytochemical, physicochemical, pharmacokinetics and docking score. The GC-MS analysis identified 27 phytoconstituents, including ethyl acetate, sclareol, 2-[1,2-dihydroxyethyl]-9-[β-d-ribofuranosyl] hypoxanthine, α-bisabolol and 2-Isopropyl-5-methylcyclohexyl 3-(1-(4-chlorophenyl)-3-oxobutyl)-coumarin-4-yl carbonate. The 27 compounds were then screened for their physicochemical and pharmacokinetic properties. The results revealed that the methanol extracts at 100 mg/mL showed significantly higher (p < 0.05) zones of inhibition (13.7 ± 1.2 mm), while the ethanol extracts at 50 mg/mL were significantly lower (6.3 ± 0.6 mm) compared to all the other treatments. The docking analysis revealed that out of the 27 compounds identified, only twelve (12) compounds have a drug-likeness activity. The 12 compounds were further subjected to docking analysis to determine the binding energies with the CTX-M protein of Klebsiella pneumoniae. Only one compound [CID_440869; (2-[1,2-dihydroxyethyl]-9-[β-d-ribofuranosyl] hypoxanthine)] had the best binding energy of −9.76 kcal/mol; hence, it can be considered a potentially suitable treatment for infections caused by ESBLs-producing strains of Klebsiella pneumoniae. This study has demonstrated that L. inermis L. extracts have antibacterial effects. Further research could explore the potential antimicrobial applications of L. inermis L. extracts to many bacterial strains.
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Effect of Lactational Low-Protein Diet on Skeletal Muscle during Adulthood and Ageing in Male and Female Mouse OffspringSarcopenia is characterised by the loss of skeletal muscle mass and function, which leads to a high risk of increased morbidity and mortality. Maternal malnutrition has been linked to impaired development of skeletal muscle of the offspring; however, there are limited studies that report the long-term effect of a maternal low-protein diet during lactation on the ageing of skeletal muscles. This study aimed to examine how a maternal low-protein diet (LPD) during lactation affects skeletal muscle ageing in the offspring. Pups born from control mothers were lactated by mothers fed with an LPD. Post-weaning, mice were either maintained on an LPD or switched to a control, normal-protein diet (NPD). In males, an LPD mainly affected the size of the myofibres without a major effect on fibre number and led to reduced grip strength in ageing mice (24 months). Female mice from mothers on an LPD had a lower body and muscle weight at weaning but caught up with control mice at 3 months. During ageing, the muscle weight, myofibre number and survival rate of female pups were significantly affected. These findings highlight the effect of an LPD during lactation on skeletal muscle ageing, the lifespan of offspring and the importance of sexual dimorphism in response to dietary challenges.
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Exploring TSGA10 Function: A Crosstalk or Controlling Mechanism in the Signaling Pathway of Carcinogenesis?Simple Summary: This research aims to explore the role of the TSGA10 protein in cancer development, specifically in how it might influence the growth and spread of cancer cells. Scientists are particularly interested in TSGA10 because it is found in both normal reproductive tissues and cancer cells, yet seems to slow down cancer progression. The key question is why cancer cells would produce a protein that could hinder their own survival. To investigate this, the authors propose several hypotheses about how TSGA10 might be involved in carcinogenesis. They will analyze both published and unpublished studies and data to understand how TSGA10 functions at different stages of cancer. By uncovering these mechanisms, this research could lead to new targeted therapies that use TSGA10 to combat cancer more effectively, offering fresh insights and potential breakthroughs in cancer treatment. Abstract: Cancer-specific antigens have been a significant area of focus in cancer treatment since their discovery in the mid-twentieth century. Cancer germline antigens are a class of antigens specifically overexpressed in germline tissues and cancer cells. Among these, TSGA10 (testis-specific gene antigen 10) is of great interest because of its crucial impact on cancer progression. Early studies explored TSGA10 expression in a variety of cancer types. More recent studies revealed that TSGA10 can suppress tumor progression by blocking cancer cell metabolism, angiogenesis, and metastasis. An open question regarding the TSGA10 is why cancer cells must express a protein that prevents their progression. To answer this question, we conducted a comprehensive review to engage the TSGA10 in the context of the current understanding of “malignant transformation”. This review demonstrated that TSGA10 expression level in cancer cells depends on the cancer stage across malignant transformation. In addition, we evaluated how TSGA10 expression can prevent the “cancer hallmarks”. Given this information, TSGA10 can be of great interest in developing effective targeted anti-cancer therapies.
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Polycystic Ovary Syndrome and the Internet of Things: A Scoping ReviewPolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder impacting women’s health and quality of life. This scoping review explores the use of the Internet of Things (IoT) in PCOS management. Results were grouped into six domains of the IoT: mobile apps, social media, wearables, machine learning, websites, and phone-based. A further domain was created to capture participants’ perspectives on using the IoT in PCOS management. Mobile apps appear to be useful for menstrual cycle tracking, symptom recording, and education. Despite concerns regarding the quality and reliability of social media content, these platforms may play an important role in disseminating PCOS-related information. Wearables facilitate detailed symptom monitoring and improve communication with healthcare providers. Machine learning algorithms show promising results in PCOS diagnosis accuracy, risk prediction, and app development. Although abundant, PCOS-related content on websites may lack quality and cultural considerations. While patients express concerns about online misinformation, they consider online forums valuable for peer connection. Using text messages and phone calls to provide feedback and support to PCOS patients may help them improve lifestyle behaviors and self-management skills. Advancing evidence-based, culturally sensitive, and accessible IoT solutions can enhance their potential to transform PCOS care, address misinformation, and empower women to better manage their symptoms.
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Time to treatment of first-episode psychosis: the role of early intervention teamsBackground/Aims: Psychosis can affect a person's functioning, quality of life and physical health. Early intervention for service users presenting with psychosis has been implemented via early intervention teams, but there are inconsistencies in assessment and treatment. The aim of this study was to examine time to treatment (defined as the commencement of antipsychotic medication) for service users experiencing first-episode psychosis, the impact of this and engagement with teams. The authors explored the effect of patient characteristics (eg gender, deprivation, ethnicity, age) and early intervention teams on time to treatment for psychosis. Methods: A retrospective cohort study was undertaken using routine data of service users accessing three early intervention teams from 2018–19. The care records of 457 service users were examined, including patient characteristics, assessments, time to first contact, treatment and time to discharge. Data were analysed using the Statistical Package for Social Sciences. Results: Use of the Positive and Negative Syndrome Scale assessment tool differed across the three early intervention teams. Engagement with all teams varied by gender. Men were particularly slow to access treatment in one team (118 of 163 service users, 72.4%). Conclusions: Increased emphasis on engaging male patients may improve service delivery. Improved communication between early intervention teams could increase standardisation of assessment and treatment.
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Cultural Adaptation and Validation of the Alzheimer’s Disease Assessment Scale – Cognitive Subscale (ADAS-Cog) - Kannada Version for a South Indian populationBackground: At present there a few culturally adapted and validated standardised neuropsychological tests for detection of persons with dementia in low-and middle income countries. Therefore, we conducted an adaptation, validation and feasibility study of the Alzheimer’s disease Assessment Scale – Cognitive Subscale (ADAS-Cog) in Kannada for use among older adults. Methods: two panels set up involving participants, subject experts and other important stakeholders. Several structured qualitative interviews informed the process of cultural adaptations (structure, content and language) the ADAS-Cog-Kannada. For the purpose of validation 120 men and women (58 of them had mild to moderate dementia and 62 of them were age and gender matched controls) were recruited. Concurrent validity was evaluated against the 10/66 Battery of Cognitive Tests in Kannada. Results: The ADAS-Cog-Kannada demonstrated internal consistency and concurrent validity. Sensitivity and Specificity for ADAS-Cog Kannada (score>14) for diagnosis of dementia were 85% and 92% respectively. It was feasible to administer ADAS-Cog in a standardised manner among community dwelling older adults and took an average of 30 minutes to administer. Conclusion: ADAS-Cog was adapted to Kannada and evaluated by employing robust methods resulting in an instrument that we believe is now culturally acceptable. Psychometric properties of ADAS-Cog Kannada were strong and linguistically acceptable. It can be used in clinical setting among Kannada speaking population and the culturally adapted.
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Heat shock proteins as danger signals to the immune systemAbstract available in hard copy
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The effect of long-term post-operative cardiac rehabilitation: a comparative intervention study in Kingdom of Saudi ArabiaAbstract available in hard copy
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The ethical dimensions of the HIV/AIDS pandemicAbstract available in hard copy
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Impact of Different Anti-Hyperglycaemic Treatments on Bone Turnover Markers and Bone Mineral Density in Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-AnalysisDiabetic bone disease (DBD) is a frequent complication in patients with type 2 diabetes mellitus (T2DM), characterised by altered bone mineral density (BMD) and bone turnover marker (BTMs) levels. The impact of different anti-diabetic medications on the skeleton remains unclear, and studies have reported conflicting results; thus, the need for a comprehensive systematic review is of paramount importance. A systematic search was conducted in PubMed and the Cochrane Library. The primary outcomes assessed were changes in BMD in relation to different anatomical sites and BTMs, including mainly P1NP and CTX as well as OPG, OCN, B-ALP and RANK-L. Risk of bias was evaluated using the JADAD score. The meta-analysis of 19 randomised controlled trials comprising 4914 patients showed that anti-diabetic medications overall increased BMD at the lumbar spine (SMD: 0.93, 95% CI [0.13, 1.73], p = 0.02), femoral neck (SMD: 1.10, 95% CI [0.47, 1.74], p = 0.0007) and in total hip (SMD: 0.33, 95% CI [−0.25, 0.92], p = 0.27) in comparison with placebo, but when compared with metformin, the overall effect favoured metformin over other treatments (SMD: −0.23, 95% CI [−0.39, −0.07], p = 0.004). GLP-1 receptor agonists and insulin analogues seem to improve BMD compared to placebo, while SGLT2 inhibitors and thiazolidinediones (TZDs) showed no significant effect, although studies’ number cannot lead to safe conclusions. For BTMs, TZDs significantly increased P1NP levels compared to placebo. However, no significant differences were observed for CTX, B-ALP, OCN, OPG, and RANK-L between anti-diabetic drugs and metformin or placebo. High heterogeneity and diverse follow-up durations among studies were evident, which obscures the validity of the results. This review highlights the variable effects of anti-diabetic drugs on DBD in T2DM patients, emphasising the need for long-term trials with robust designs to better understand these relationships and inform clinical decisions.