المؤلفون: Francesca Amitrano, Mohanraj Krishnan, Rinki Murphy, Karaponi A. M. Okesene-Gafa, Maria Ji, John M. D. Thompson, Rennae S. Taylor, Tony R. Merriman, Elaine Rush, Megan McCowan, Lesley M. E. McCowan, Christopher J. D. McKinlay

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-8 (2024)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract In Māori and Pacific adults, the CREBRF rs373863828 minor (A) allele is associated with increased body mass index (BMI) but reduced incidence of type-2 and gestational diabetes mellitus. In this prospective cohort study of Māori and Pacific infants, nested within a nutritional intervention trial for pregnant women with obesity and without pregestational diabetes, we investigated whether the rs373863828 A allele is associated with differences in growth and body composition from birth to 12–18 months’ corrected age. Infants with and without the variant allele were compared using generalised linear models adjusted for potential confounding by gestation length, sex, ethnicity and parity, and in a secondary analysis, additionally adjusted for gestational diabetes. Carriage of the rs373863828 A allele was not associated with altered growth and body composition from birth to 6 months. At 12–18 months, infants with the rs373863828 A allele had lower whole-body fat mass [FM 1.4 (0.7) vs. 1.7 (0.7) kg, aMD −0.4, 95% CI −0.7, 0.0, P = 0.05; FM index 2.2 (1.1) vs. 2.6 (1.0) kg/m2 aMD −0.6, 95% CI −1.2,0.0, P = 0.04]. However, this association was not significant after adjustment for gestational diabetes, suggesting that it may be mediated, at least in part, by the beneficial effect of CREBRF rs373863828 A allele on maternal glycemic status.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/3bb8c25da84740a18bf61094b630c9e6Test

المؤلفون: Matire Harwood, Jacqueline Ramke, Rinki Murphy, Braden Te Ao, Pushkar Raj Silwal, Claire O'Shea, Alehandrea Manuel

المصدر: BMJ Open, Vol 14, Iss 3 (2024)

مصطلحات موضوعية: Medicine

الوصف: Introduction The global population is ageing, and by 2050, there will be almost 2.1 billion people over the age of 60 years. This ageing population means conditions such as diabetes are on the increase, as well as other conditions associated with ageing (and/or diabetes), including those that cause vision impairment, hearing impairment or foot problems. The aim of this scoping review is to identify the extent of the literature describing integration of services for adults of two or more of diabetes, eye, hearing or foot services.Methods and analysis The main database searches are of Medline and Embase, conducted by an information specialist, without language restrictions, for studies published from 1 January 2000 describing the integration of services for two or more of diabetes, eye, hearing and foot health in the private or public sector and at the primary or secondary level of care, primarily targeted to adults aged ≥40 years. A grey literature search will focus on websites of key organisations. Reference lists of all included articles will be reviewed to identify further studies. Screening and data extraction will be undertaken by two reviewers independently and any discrepancies will be resolved by discussion. We will use tables, maps and text to summarise the included studies and findings, including where studies were undertaken, which services tended to be integrated, in which sector and level of the health system, targeting which population groups and whether they were considered effective.Ethics and dissemination As our review will be based on published data, ethical approval will not be sought. This review is part of a project in Aotearoa New Zealand that aims to improve access to services for adults with diabetes or eye, hearing or foot conditions. The findings will be published in a peer-reviewed journal and presented at relevant conferences.

وصف الملف: electronic resource

العلاقة: https://bmjopen.bmj.com/content/14/3/e082225.fullTest; https://doaj.org/toc/2044-6055Test

الوصول الحر: https://doaj.org/article/f070d2fcc8434ddb94ddd13fe6b8d102Test

المؤلفون: Rinki Murphy, Kevin Colclough, Toni I. Pollin, Jennifer M. Ikle, Pernille Svalastoga, Kristin A. Maloney, Cécile Saint-Martin, Janne Molnes, ADA/EASD PMDI, Shivani Misra, Ingvild Aukrust, Elisa de Franco, Sarah E. Flanagan, Pål R. Njølstad, Liana K. Billings, Katharine R. Owen, Anna L. Gloyn

المصدر: Communications Medicine, Vol 3, Iss 1, Pp 1-24 (2023)

مصطلحات موضوعية: Medicine

الوصف: Abstract Background Monogenic diabetes presents opportunities for precision medicine but is underdiagnosed. This review systematically assessed the evidence for (1) clinical criteria and (2) methods for genetic testing for monogenic diabetes, summarized resources for (3) considering a gene or (4) variant as causal for monogenic diabetes, provided expert recommendations for (5) reporting of results; and reviewed (6) next steps after monogenic diabetes diagnosis and (7) challenges in precision medicine field. Methods Pubmed and Embase databases were searched (1990-2022) using inclusion/exclusion criteria for studies that sequenced one or more monogenic diabetes genes in at least 100 probands (Question 1), evaluated a non-obsolete genetic testing method to diagnose monogenic diabetes (Question 2). The risk of bias was assessed using the revised QUADAS-2 tool. Existing guidelines were summarized for questions 3-5, and review of studies for questions 6-7, supplemented by expert recommendations. Results were summarized in tables and informed recommendations for clinical practice. Results There are 100, 32, 36, and 14 studies included for questions 1, 2, 6, and 7 respectively. On this basis, four recommendations for who to test and five on how to test for monogenic diabetes are provided. Existing guidelines for variant curation and gene-disease validity curation are summarized. Reporting by gene names is recommended as an alternative to the term MODY. Key steps after making a genetic diagnosis and major gaps in our current knowledge are highlighted. Conclusions We provide a synthesis of current evidence and expert opinion on how to use precision diagnostics to identify individuals with monogenic diabetes.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2730-664XTest

الوصول الحر: https://doaj.org/article/4cfa59670e5f4584a6699dc739a2fd7bTest

المؤلفون: Charisse Y.-J. Kuo, Ilva D. Rupenthal, Michael Booth, Rinki Murphy, Odunayo O. Mugisho

المصدر: Future Pharmacology, Vol 3, Iss 3, Pp 612-624 (2023)

مصطلحات موضوعية: diabetic retinopathy, progression, NLRP3, inflammasome, systemic, prediction, Therapeutics. Pharmacology, RM1-950

الوصف: The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) protein 3 (NLRP3) inflammasome pathway is believed to mediate chronic inflammation in diabetic retinopathy (DR); however, its impact on the progression of DR remains to be elucidated. Therefore, the primary aim of this pilot study was to determine whether systemic inflammasome biomarkers interleukin (IL)-1β and IL-18 can be used to predict DR progression. DR screening results were analyzed against weight, level of glycated hemoglobin (HbA1c), and plasma levels of inflammasome biomarkers (IL-1β and IL-18), as well as general inflammation markers (C-reactive protein (CRP), IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor (VEGF)) in patients with type 2 diabetes at baseline and 1 year post-bariatric surgery. Cross-sectional analysis demonstrated that weight, HbA1c, CRP, and IL-18 did not correlate with DR severity. The progressed group showed a higher relative change in IL-18 and CRP levels compared to the stable and regressed groups. Furthermore, relative changes in plasma CRP levels correlated with those of IL-18. Although further validation with larger cohorts is necessary, this pilot study supports the hypothesis that systemic inflammasome activation is associated with DR progression.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2673-9879/3/3/39Test; https://doaj.org/toc/2673-9879Test

الوصول الحر: https://doaj.org/article/66fce5b360ac4b8fa362ecca7138fb52Test

المؤلفون: Jaye Moors, Mohanraj Krishnan, Nick Sumpter, Riku Takei, Matt Bixley, Murray Cadzow, Tanya J. Major, Amanda Phipps-Green, Ruth Topless, Marilyn Merriman, Malcolm Rutledge, Ben Morgan, Jenna C. Carlson, Jerry Z. Zhang, Emily M. Russell, Guangyun Sun, Hong Cheng, Daniel E. Weeks, Take Naseri, Muagututi’a Sefuiva Reupena, Satupa’itea Viali, John Tuitele, Nicola L. Hawley, Ranjan Deka, Stephen T. McGarvey, Janak de Zoysa, Rinki Murphy, Nicola Dalbeth, Lisa Stamp, Mele Taumoepeau, Frances King, Phillip Wilcox, Nuku Rapana, Sally McCormick, Ryan L. Minster, Tony R. Merriman, Megan Leask

المصدر: HGG Advances, Vol 4, Iss 3, Pp 100204- (2023)

مصطلحات موضوعية: CETP, Māori, Pacific, Association analyses, HDL-C, Lipids, Genetics, QH426-470

الوصف: Summary: Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2666247723000362Test; https://doaj.org/toc/2666-2477Test

الوصول الحر: https://doaj.org/article/7af5bffb2a1a41c9a4a3264dd197c255Test

المؤلفون: Zanetta Toomata, Megan Leask, Mohanraj Krishnan, Murray Cadzow, Nicola Dalbeth, Lisa K. Stamp, Janak de Zoysa, Tony Merriman, Phillip Wilcox, Ofa Dewes, Rinki Murphy

المصدر: Frontiers in Endocrinology, Vol 14 (2023)

مصطلحات موضوعية: precision medicine, monogenic diabetes, type 2 diabetes, molecular diagnosis, maturity-onset diabetes of the young (MODY), maternally inherited diabetes and deafness (MIDD), Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: AimsMonogenic diabetes accounts for 1-2% of diabetes cases yet is often misdiagnosed as type 2 diabetes. The aim of this study was to examine in Māori and Pacific adults clinically diagnosed with type 2 diabetes within 40 years of age, (a) the prevalence of monogenic diabetes in this population (b) the prevalence of beta-cell autoantibodies and (c) the pre-test probability of monogenic diabetes.MethodsTargeted sequencing data of 38 known monogenic diabetes genes was analyzed in 199 Māori and Pacific peoples with BMI of 37.9 ± 8.6 kg/m2 who had been diagnosed with type 2 diabetes between 3 and 40 years of age. A triple-screen combined autoantibody assay was used to test for GAD, IA-2, and ZnT8. MODY probability calculator score was generated in those with sufficient clinical information (55/199).ResultsNo genetic variants curated as likely pathogenic or pathogenic were found. One individual (1/199) tested positive for GAD/IA-2/ZnT8 antibodies. The pre-test probability of monogenic diabetes was calculated in 55 individuals with 17/55 (31%) scoring above the 20% threshold considered for diagnostic testing referral.DiscussionOur findings suggest that monogenic diabetes is rare in Māori and Pacific people with clinical age, and the MODY probability calculator likely overestimates the likelihood of a monogenic cause for diabetes in this population.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fendo.2023.1174699/fullTest; https://doaj.org/toc/1664-2392Test

الوصول الحر: https://doaj.org/article/1976fa2455f24ce3a4d3e3c2d39adc29Test

المؤلفون: Charisse Y. J. Kuo, Rinki Murphy, Ilva D. Rupenthal, Odunayo O. Mugisho

المصدر: BMC Ophthalmology, Vol 22, Iss 1, Pp 1-13 (2022)

مصطلحات موضوعية: Diabetic retinopathy, Inflammasome, Biomarkers, Vitreous, Serum, Cytokines, Ophthalmology, RE1-994

الوصف: Abstract Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome pathway has been implicated in Diabetic retinopathy (DR) pathogenesis, but its impact on DR development and progression remains unclear. Therefore, the primary aim of this systematic literature review was to determine the role of the inflammasome in DR development. Furthermore, the secondary aim was to determine whether systemic inflammasome activity can be used to predict DR progression. Studies measuring vitreous and/or serum inflammasome biomarkers in DR patients with Type 2 Diabetes Mellitus (T2DM) were searched systematically using online databases EMBASE, PubMed and Web of Science with the last search conducted on 29th of September 2021. The risk of bias was assessed using the Newcastle Ottawa Scale and 20 studies were eligible for narrative analysis. Limitations included the heterogeneity in detection assays used, the small and uneven sample size, a lack of vitreous data in earlier disease stages, and not accounting for patients with other systemic co-morbidities. Analysis showed that inflammasome biomarkers IL-1β and IL-18 increased significantly from non-proliferative DR to proliferative DR in both vitreous and serum, suggesting the inflammasome pathway is activated as DR progresses and that serum inflammasome levels could be explored as potential biomarkers for DR progression.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2415Test

الوصول الحر: https://doaj.org/article/e4faf2fec8c24f81ad997c7b0d8b27f0Test

المؤلفون: Francesca Harrington, Mark Greenslade, Kevin Colclough, Ryan Paul, Craig Jefferies, Rinki Murphy

المصدر: Frontiers in Endocrinology, Vol 14 (2023)

مصطلحات موضوعية: monogenic diabetes, New Zealand, MODY, genomics, genetic testing, Aotearoa (New Zealand), Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: AimsTo evaluate (a) the diagnostic yield of genetic testing for monogenic diabetes when using single gene and gene panel-based testing approaches in the New Zealand (NZ) population, (b) whether the MODY (Maturity Onset Diabetes of the Young) pre-test probability calculator can be used to guide referrals for testing in NZ, (c) the number of referrals for testing for Māori/Pacific ethnicities compared to NZ European, and (d) the volume of proband vs cascade tests being requested.MethodsA retrospective audit of 495 referrals, from NZ, for testing of monogenic diabetes genes was performed. Referrals sent to LabPlus (Auckland) laboratory for single gene testing or small multi-gene panel testing, or to the Exeter Genomics Laboratory, UK, for a large gene panel, received from January 2014 – December 2021 were included. Detection rates of single gene, small multi-gene and large gene panels (neonatal and non-neonatal), and cascade testing were analysed. Pre-test probability was calculated using the Exeter MODY probability calculator and ethnicity data was also collected.ResultsThe diagnostic detection rate varied across genes, from 32% in GCK, to 2% in HNF4A, with single gene or small gene panel testing averaging a 12% detection rate. Detection rate by type of panel was 9% for small gene panel, 23% for non-neonatal monogenic diabetes large gene panel and 40% for neonatal monogenic diabetes large gene panel. 45% (67/147) of patients aged 1-35 years at diabetes diagnosis scored

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fendo.2023.1116880/fullTest; https://doaj.org/toc/1664-2392Test

الوصول الحر: https://doaj.org/article/06c53f57d4af4998b7d4189d2be5ab7eTest

المؤلفون: Tanya Symons, Janelle Bowden, Anne McKenzie, Julia M Fallon-Ferguson, Leanne Y Weekes, James Ansell, Rinki Murphy, Shilpa Jesudason, Manoj Saxena, Alistair Nichol, Nicola Straiton

المصدر: Public Health Research & Practice, Vol 33, Iss 1 (2023)

مصطلحات موضوعية: clinical trials, consumers, Public aspects of medicine, RA1-1270

الوصف: Objective: This manuscript describes the novel approach to developing a toolkit to support meaningful consumer involvement in clinical trials in Australia to help guide others in considering the development of similar resources.The toolkit aims to support greater consumer involvement in shaping how clinical research is prioritised, designed and conducted. Type of program or service: A working group of researchers, research organisations and consumers was established to co-develop the Consumer Involvement and Engagement Toolkit (the ‘Toolkit’), a digital resource to guide researchers and organisations regarding consumer involvement in clinical trials. Findings: A literature review and international scan of best practice revealed numerous resources outlining best practice for consumer involvement in clinical research and clear evidence of its impact and value. Through a novel content-sharing process, we were able to utilise these resources to develop a comprehensive Toolkit for researchers and research organisations that provides world-class guidance. Lessons learnt: There is a growing movement to ensure consumer involvement in healthcare, including in clinical research. We discovered its proponents were willing to share their tools and resources to promote international consumer involvement. Although these international tools and resources needed adaptation to suit the Australian research environment, this was achievable with far less effort than developing them from scratch.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2204-2091Test

الوصول الحر: https://doaj.org/article/8a5098a7ec304d9aa227dd3d7b5f4a4bTest

المؤلفون: Haribalan Kumar, Robby Green, Daniel M. Cornfeld, Paul Condron, Taylor Emsden, Ayah Elsayed, Debbie Zhao, Kat Gilbert, Martyn P. Nash, Alys R. Clark, Merryn H. Tawhai, Kelly Burrowes, Rinki Murphy, Maryam Tayebi, Josh McGeown, Eryn Kwon, Vickie Shim, Alan Wang, Julie Choisne, Laura Carman, Thor Besier, Geoffrey Handsfield, Thiranja Prasad Babarenda Gamage, Jiantao Shen, Gonzalo Maso Talou, Soroush Safaei, Jerome J. Maller, Davidson Taylor, Leigh Potter, Samantha J. Holdsworth, Graham A. Wilson

المصدر: Frontiers in Physiology, Vol 14 (2023)

مصطلحات موضوعية: MRI image analysis, computational modelling, child health and development, neuroimage analysis, radiology, Physiology, QP1-981

الوصف: Our study methodology is motivated from three disparate needs: one, imaging studies have existed in silo and study organs but not across organ systems; two, there are gaps in our understanding of paediatric structure and function; three, lack of representative data in New Zealand. Our research aims to address these issues in part, through the combination of magnetic resonance imaging, advanced image processing algorithms and computational modelling. Our study demonstrated the need to take an organ-system approach and scan multiple organs on the same child. We have pilot tested an imaging protocol to be minimally disruptive to the children and demonstrated state-of-the-art image processing and personalized computational models using the imaging data. Our imaging protocol spans brain, lungs, heart, muscle, bones, abdominal and vascular systems. Our initial set of results demonstrated child-specific measurements on one dataset. This work is novel and interesting as we have run multiple computational physiology workflows to generate personalized computational models. Our proposed work is the first step towards achieving the integration of imaging and modelling improving our understanding of the human body in paediatric health and disease.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fphys.2023.1104838/fullTest; https://doaj.org/toc/1664-042XTest

الوصول الحر: https://doaj.org/article/0fc92b6f4a7640d8a8cdd81453f039bdTest