Medicine and Health Sciences Commons^™

Facial Dermatosis Papulosa Nigra, A Risk For The Development Of Pterygium And Myopia: A Descriptive Cross-Sectional Study In Ghana, Du Bois Asante, Korantema M. Tsegah, Ebenezer Afrifa-Yamoah, Samuel Kyei, Dunyah J. Dzidzor, Reindolf Anokye

Research outputs 2022 to 2026

Background: Dermatosis papulosa nigra (DPN) affects sun-exposed areas such as the face, neck, and trunk. The prevalence of pterygium and myopia in DPN patients in Ghana has not been studied. In this study, we examined the risk and protective factors for pterygium and myopia in DPN patients. Materials and Methods: The study involved 100 participants with facial DPN. A standard ophthalmic exam was performed using a portable slit lamp and a 3.5 X magnified loop. Participants completed a closed-ended questionnaire. Logistic regression was used to summarize the level of association between DPN, myopia, and pterygium, as well as demographic factors …

Machine Learning Of Plasma Metabolome Identifies Biomarker Panels For Metabolic Syndrome: Findings From The China Suboptimal Health Cohort, Hao Wang, Youxin Wang, Xingang Li, Xuan Deng, Yuanyuan Kong, Wei Wang, Yong Zhou

Research outputs 2022 to 2026

Background: Metabolic syndrome (MetS) has been proposed as a clinically identifiable high-risk state for the prediction and prevention of cardiovascular diseases and type 2 diabetes mellitus. As a promising “omics” technology, metabolomics provides an innovative strategy to gain a deeper understanding of the pathophysiology of MetS. The study aimed to systematically investigate the metabolic alterations in MetS and identify biomarker panels for the identification of MetS using machine learning methods. Methods: Nuclear magnetic resonance-based untargeted metabolomics analysis was performed on 1011 plasma samples (205 MetS patients and 806 healthy controls). Univariate and multivariate analyses were applied to identify metabolic biomarkers …

Relationship Of Cognition And Alzheimer’S Disease With Gastrointestinal Tract Disorders: A Large-Scale Genetic Overlap And Mendelian Randomisation Analysis, Emmanuel O. Adewuyi, Eleanor K. O’Brien, Tenielle Porter, Simon M. Laws

Research outputs 2022 to 2026

Emerging observational evidence suggests links between cognitive impairment and a range of gastrointestinal tract (GIT) disorders; however, the mechanisms underlying their relationships remain unclear. Leveraging large-scale genome-wide association studies’ summary statistics, we comprehensively assessed genetic overlap and potential causality of cognitive traits and Alzheimer’s disease (AD) with several GIT disorders. We demonstrate a strong and highly significant inverse global genetic correlation between cognitive traits and GIT disorders — peptic ulcer disease (PUD), gastritis-duodenitis, diverticulosis, irritable bowel syndrome, and gastroesophageal reflux disease (GERD), but not inflammatory bowel disease (IBD). Further analysis detects 35 significant (p < 4.37 × 10 ^{− 5}) bivariate local genetic …

Combined Evaluation Of Arterial Stiffness, Glycemic Control And Hypertension For Macrovascular Complications In Type 2 Diabetes, Zhiyuan Wu, Siqi Yu, Haiping Zhang, Zheng Guo, Yulu Zheng, Zongkai Xu, Zhiwei Li, Xiangtong Liu, Xia Li, Shuo Chen, Jingbo Zhang, Lixin Tao, Xiuhua Guo

Research outputs 2022 to 2026

Background: Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication. Methods: A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0 – 4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95 …

Assessment Of A Polygenic Hazard Score For The Onset Of Pre-Clinical Alzheimer’S Disease, Michael Vacher, Vincent Doré, Tenielle Porter, Lidija Milicic, Victor L. Villemagne, Pierrick Bourgeat, Sam C. Burnham, Timothy Cox, Colin L. Masters, Christopher C. Rowe, Jurgen Fripp, James D. Doecke, Simon M. Laws

Research outputs 2022 to 2026

Background: With a growing number of loci associated with late-onset (sporadic) Alzheimer’s disease (AD), the polygenic contribution to AD is now well established. The development of polygenic risk score approaches have shown promising results for identifying individuals at higher risk of developing AD, thereby facilitating the development of preventative and therapeutic strategies. A polygenic hazard score (PHS) has been proposed to quantify age-specific genetic risk for AD. In this study, we assessed the predictive power and transferability of this PHS in an independent cohort, to support its clinical utility. Results: Using genotype and imaging data from 780 individuals enrolled in …

Comprehensive Genetic Analysis Of The Human Lipidome Identifies Loci Associated With Lipid Homeostasis With Links To Coronary Artery Disease, Gemma Cadby, Corey Giles, Phillip E. Melton, Kevin Huynh, Natalie A. Mellett, Thy Duong, Anh Nguyen, Michelle Cinel, Alex Smith, Gavriel Olshansky, Tingting Wang, Marta Brozynska, Mike Inouye, Nina S. Mccarthy, Amir Ariff, Joseph Hung, Jennie Hui, John Beilby, Marie Pierre Dubé, Gerald F. Watts, Sonia Shah, Naomi R. Wray, Wei Ling Florence Lim, Pratishtha Chatterjee, Ian Martins, Simon M. Laws, Tenielle Porter, Michael Vacher, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Kevin Taddei, Matthias Arnold, Gabi Kastenmüller, Kwangsik Nho, Andrew J. Saykin, Xianlin Han, Rima Kaddurah-Daouk, Ralph N. Martins, John Blangero, Peter J. Meikle, Eric K. Moses

Research outputs 2022 to 2026

We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid species in serum from 4,492 individuals from the Busselton Health Study. The discovery GWAS identified 3,361 independent lipid-loci associations, involving 667 genomic regions (479 previously unreported), with validation in two independent cohorts. A meta-analysis revealed an additional 70 independent genomic regions associated with lipid species. We identified 134 lipid endophenotypes for CAD associated with 186 genomic loci. Associations between independent lipid-loci with coronary atherosclerosis were …

Association Of Visceral Adiposity Index With Incident Nephropathy And Retinopathy: A Cohort Study In The Diabetic Population, Zhiyuan Wu, Siqi Yu, Xiaoping Kang, Yue Liu, Zongkai Xu, Zhiwei Li, Jinqi Wang, Xinlei Miao, Xiangtong Liu, Xia Li, Jingbo Zhang, Wei Wang, Lixin Tao, Xiuhua Guo

Research outputs 2022 to 2026

Background: The association between visceral adiposity index (VAI) and diabetic complications has been reported in cross-sectional studies, while the effect of VAI on complication development remains unclear. This study aims to evaluate the longitudinal association of VAI and Chinese VAI (CVAI) with the incidence of diabetic nephropathy and retinopathy using a Chinese cohort. Methods: A total of 8 948 participants with type 2 diabetes from Beijing Health Management Cohort were enrolled during 2013–2014, and followed until December 31, 2019. Nephropathy was confirmed by urine albumin/creatinine ratio and estimated glomerular filtration rate; retinopathy was diagnosed using fundus photograph. Results: The mean …

Immunoglobulin G N-Glycan, Inflammation And Type 2 Diabetes In East Asian And European Populations: A Mendelian Randomization Study, Biyan Wang, Di Liu, Manshu Song, Wei Wang, Bo Guo, Youxin Wang

Research outputs 2022 to 2026

Background: Immunoglobulin G (IgG) N-glycans have been shown to be associated with the risk of type 2 diabetes (T2D) and its risk factors. However, whether these associations reflect causal effects remain unclear. Furthermore, the associations of IgG N-glycans and inflammation are not fully understood. Methods: We examined the causal associations of IgG N-glycans with inflammation (C-reactive protein (CRP) and fibrinogen) and T2D using two-sample Mendelian randomization (MR) analysis in East Asian and European populations. Genetic variants from IgG N-glycan quantitative trait loci (QTL) data were used as instrumental variables. Two-sample MR was conducted for IgG N-glycans with inflammation (75,391 and …

Genetic Liability Between Covid-19 And Heart Failure: Evidence From A Bidirectional Mendelian Randomization Study, Huachen Wang, Zheng Guo, Yulu Zheng, Bing Chen

Research outputs 2022 to 2026

Background: Previous studies have observed inconsistent associations between coronavirus disease 2019 (COVID-19) and heart failure (HF), but these studies were prone to bias based on reverse causality and residual confounding factors. We aimed to investigate genetic liability between COVID-19 and heart failure using a bidirectional Mendelian randomization study. Methods: The causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and HF are determined by using a bidirectional Mendelian randomization analysis. We drew on summary statistics from the largest HF genome-wide association study (GWAS) meta-analysis on individuals of European ancestry, which included 47,309 HF …

Vascular Endothelial Growth Factor And The Risk Of Venous Thromboembolism: A Genetic Correlation And Two-Sample Mendelian Randomization Study, Qiaoyun Zhang, Xiaoyu Zhang, Jie Zhang, Biyan Wang, Qiuyue Tian, Xiaoni Meng, Jinxia Zhang, Mengyang Jiang, Yiqiang Zhang, Deqiang Zheng, Lijuan Wu, Wei Wang, Baoguo Wang, Youxin Wang

Research outputs 2022 to 2026

Background: The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE. Methods: Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score …

Association Of Cumulative Monocyte To High-Density Lipoprotein Ratio With The Risk Of Type 2 Diabetes: A Prospective Cohort Study, Dan Wu, Yulong Lan, Yuancheng Xu, Songna Xu, Yuejun Huang, Lois Balmer, Gehendra Maharra, Wencan Xu, Wei Wang, Shouling Wu

Research outputs 2022 to 2026

Background: Recent studies have established that monocyte-derived inflammation plays a central role in the pathogenesis of type 2 diabetes mellitus (T2DM). It is unclear whether chronic metabolic inflammation, reflected by the cumulative monocyte to high-density lipoprotein ratio (CumMHR), predisposes the general population to T2DM. Methods: This study included 40,813 participants without diabetes from a real-life, community-based cohort (the Kailuan Study) attending a 2-year cycle of health survey since 2006. Cumulative exposure was obtained from 2006/2007 to 2010/2011. Follow-up started at 2010/2011 and through 2020. Multivariable-adjusted Cox regression models were used to calculate the CumMHR-associated risk of incident T2DM. Results: Over …

Bidirectional Associations Between Daytime Napping Duration And Metabolic Syndrome: A Nationally Representative Cohort Study, Jinqi Wang, Zhiyuan Wu, Xiaohan Jin, Rui Jin, Ze Han, Haiping Zhang, Zongkai Xu, Yue Liu, Xiuhua Guo, Lixin Tao

Research outputs 2022 to 2026

Background: We aimed to examine the bidirectional associations between daytime napping duration and metabolic syndrome (MetS). Methods: Using data from the China Health and Retirement Longitudinal Study from 2011 to 2015, modified Poisson regression models were performed to explore the longitudinal associations of baseline napping duration with the occurrence and remission of MetS. Generalized estimating equation was conducted to explore the association between baseline MetS status with subsequent changes in daytime napping duration. Cross-lagged panel analysis was performed to further verify their bidirectional relationships. Results: During the four-year follow-up, among 5041 participants without MetS at baseline, extended naps were significantly …

Current Insights On The Use Of Insulin And The Potential Use Of Insulin Mimetics In Targeting Insulin Signalling In Alzheimer’S Disease, Amy Woodfield, Tatiana Gonzales, Erik Helmerhorst, Simon Laws, Philip Newsholme, Tenielle Porter, Giuseppe Verdile

Research outputs 2022 to 2026

Alzheimer’s disease (AD) and type 2 diabetes (T2D) are chronic diseases that share several pathological mechanisms, including insulin resistance and impaired insulin signalling. Their shared features have prompted the evaluation of the drugs used to manage diabetes for the treatment of AD. Insulin delivery itself has been utilized, with promising effects, in improving cognition and reducing AD related neuropathology. The most recent clinical trial involving intranasal insulin reported no slowing of cognitive decline; however, several factors may have impacted the trial outcomes. Long-acting and rapid-acting insulin analogues have also been evaluated within the context of AD with a lack of …

Apoe Ε2 Resilience For Alzheimer’S Disease Is Mediated By Plasma Lipid Species: Analysis Of Three Independent Cohort Studies, Tingting Wang, Kevin Huynh, Corey Giles, Natalie A. Mellett, Thy Duong, Anh Nguyen, Wei L. F. Lim, Alex A. T. Smith, Gavriel Olshansky, Gemma Cadby, Joseph Hung, Jennie Hui, John Beilby, Gerald F. Watts, Pratishtha Chatterjee, Ian Martins, Simon Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Kevin Taddei, Vincent Doré, Jürgen Fripp, Matthias Arnold, Gabi Kastenmüller, Kwangsik Nho, Andrew J. Saykin, Rebecca Baillie, Xianlin Han, Ralph N. Martins, Eric K. Moses, Rima Kaddurah-Daouk, Peter J. Meikle

Research outputs 2022 to 2026

Introduction:

The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood.

Methods:

We performed lipidomic analysis on three independent cohorts (the Australian Imaging, Biomarkers and Lifestyle [AIBL] flagship study, n = 1087; the Alzheimer's Disease Neuroimaging Initiative [ADNI] 1 study, n = 819; and the Busselton Health Study [BHS], n = 4384), and we defined associations between APOE ε2 and ε4 and 569 plasma/serum lipid species. Mediation analysis defined the proportion of the treatment effect of the APOE …

Monitoring Quality Of Care In Hepatocellular Carcinoma: A Modified Delphi Consensus, Ashika D. Maharaj, John Lubel, Eileen Lam, Paul J. Clark, Oliver Duncan, Jacob George, Gary P. Jeffrey, Lara Lipton, Howard Liu, Geoffrey Mccaughan, Eu-Ling Neo, Jennifer Philip, Simone I. Strasser, Katherine Stuart, Alexander Thompson, Jonathan Tibballs, Thomas Tu, Michael C. Wallace, Alan Wigg, Marnie Wood, Amany Zekry, Elysia Greenhill, Liane J. Ioannou, Golo Ahlenstiel, Kaye Bowers, Stephen J. Clarke, Anouk Dev, Michael Fink, Mark Goodwin, Christos S. Karapetis, Miriam T. Levy, Kate Muller, James O'Beirne, David Pryor, James Seow, Nicholas Shackel, Caroline Tallis, Nick Butler, John K. Olynyk, Kate Reed-Cox, John R. Zalcberg, Stuart K. Roberts

Research outputs 2022 to 2026

Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two-round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC …

Resistant Starch As A Dietary Intervention To Limit The Progression Of Diabetic Kidney Disease, Anna M. Drake, Melinda T. Coughlan, Claus T. Christophersen, Matthew Snelson

Research outputs 2022 to 2026

Diabetes is the leading cause of kidney disease, and as the number of individuals with diabetes increases there is a concomitant increase in the prevalence of diabetic kidney disease (DKD). Diabetes contributes to the development of DKD through a number of pathways, including inflammation, oxidative stress, and the gut-kidney axis, which may be amenable to dietary therapy. Resistant starch (RS) is a dietary fibre that alters the gut microbial consortium, leading to an increase in the microbial production of short chain fatty acids. Evidence from animal and human studies indicate that short chain fatty acids are able to attenuate inflammatory …

Social Ecological Influences On Treatment Decision-Making In Men Diagnosed With Low Risk, Localised Prostate Cancer, Megan Mcintosh, Melissa J. Opozda, Camille E. Short, Daniel A. Galvão, Rebecca Tutino, Michael Diefenbach, Behfar Ehdaie, Christian Nelson

Research outputs 2022 to 2026

Objective: Individuals diagnosed with low risk, localised prostate cancer (PCa) face a difficult decision between active surveillance (AS) and definitive treatment. We aimed to explore perceived influences on treatment decision-making from the patient and partner's perspectives. Methods: Patients (and partners) who met AS criteria and had chosen their treatment were recruited. Semi-structured individual interviews were conducted via telephone to explore experiences of diagnosis, impact on patient lifestyle, experiences with physicians, treatment preferences/choice, treatment information understanding and needs, and overall decision-making process. Interviews were audio recorded, transcribed verbatim, and analysed using Reflexive Thematic Analysis. Results: Twenty-four male patients (18 chose AS) …

Dysnatremia Is Associated With Increased Risk Of All-Cause Mortality Within 365 Days Post-Discharge In Patients With Atrial Fibrillation Without Heart Failure: A Prospective Cohort Study, Yan Zhou, Dong Lin, Shiwan Wu, Jiaxin Xiao, Min Yu, Zhongbo Xiao, Muli Wu, Zhisheng Chen, Cuihong Tian, Rongbing Chen, Yequn Chen, Xuerui Tan

Research outputs 2022 to 2026

Aim: The aim of this study is to evaluate the association between serum sodium concentrations at hospital admission and all-cause mortality within 365 days post-discharge in patients with atrial fibrillation (AF) without heart failure (HF). Methods: The prospective cohort study enrolled 1,446 patients with AF without HF between November 2018 and October 2020. A follow-up was performed 30, 90, 180, and 365 days after enrollment through outpatient visits or telephone interviews. All-cause mortality was estimated in three groups according to serum sodium concentrations: hyponatremia ( < 135 mmol/L), normonatremia (135 – 145 mmol/L), and hypernatremia ( > 145 mmol/L). We estimated the risk of all-cause mortalities using univariable and multivariable Cox proportional …

Plasma High-Density Lipoprotein Cargo Is Altered In Alzheimer's Disease And Is Associated With Regional Brain Volume, Steve Pedrini, James D. Doecke, Eugene Hone, Penghao Wang, Rohith Thota, Ashley I. Bush, Christopher C. Rowe, Vincent Dore, Victor L. Villemagne, David Ames, Stephanie Rainey-Smith, Giuseppe Verdile, Hamid R. Sohrabi, Manfred R. Raida, Kevin Taddei, Sam Gandy, Colin L. Masters, Pratishtha Chatterjee, Ralph N. Martins, Aibl Research Group

Research outputs 2022 to 2026

Cholesterol levels have been repeatedly linked to Alzheimer's Disease (AD), suggesting that high levels could be detrimental, but this effect is likely attributed to Low-Density Lipoprotein (LDL) cholesterol. On the other hand, High-Density Lipoproteins (HDL) cholesterol levels have been associated with reduced brain amyloidosis and improved cognitive function. However, recent findings have suggested that HDL-functionality, which depends upon the HDL-cargo proteins associated with HDL, rather than HDL levels, appears to be the key factor, suggesting a quality over quantity status. In this report, we have assessed the HDL-cargo (Cholesterol, ApoA-I, ApoA-II, ApoC-I, ApoC-III, ApoD, ApoE, ApoH, ApoJ, CRP, and SAA) …

The Reported External Traumas Among People With Diabetes-Related Foot Ulcers And Their Outcomes: A Systematic Review Of Case Reports, Ma'en Zaid Abu-Qamar, Vivien Kemp, Lisa Whitehead

Research outputs 2022 to 2026

The objective of this systematic review was to collate evidence published in case reports on the reported origins of external traumas that contribute to the development of diabetic foot ulcers and their outcomes. The review also aimed to suggest reporting criteria for external traumas contributing to the development of diabetic foot ulcers. The search strategy led to the identification of 1224 articles across six electronic databases. Additional articles were also sourced from other electronic platforms (Google scholar) and the reference lists of the included case reports. Ninety-four articles met the inclusion criteria and were published between 1989 and 2020. The …

Consecutive Dosing Of Uvb Irradiation Induces Loss Of Abcb5 Expression And Activation Of Emt And Fibrosis Proteins In Limbal Epithelial Cells Similar To Pterygium Epithelium, M. Domdey, M. A. Kluth, C. Maßlo, C. Ganss, Markus H. Frank, N. Y. Frank, M. T. Coroneo, C. Cursiefen, M. Notara

Research outputs 2022 to 2026

Pterygium pathogenesis is often attributed to a population of altered limbal stem cells, which initiate corneal invasion and drive the hyperproliferation and fibrosis associated with the disease. These cells are thought to undergo epithelial to mesenchymal transition (EMT) and to contribute to subepithelial stromal fibrosis. In this study, the presence of the novel limbal stem cell marker ABCB5 in clusters of basal epithelial pterygium cells co-expressing with P63α and P40 is reported. ABCB5-positive pterygium cells also express EMT-associated fibrosis markers including vimentin and α-SMA while their β-catenin expression is reduced. By using a novel in vitro model of two-dose UV-induced …

Arthritis Prediction Of Advanced Hepatic Fibrosis In Hfe Hemochromatosis, Lauren Andersson, Lawrie W. Powell, Louise E. Ramm, Grant A. Ramm, John K. Olynyk

Research outputs 2022 to 2026

Objective: To evaluate whether arthritis predicts the likelihood of advanced hepatic fibrosis in HFE hemochromatosis. Patients and Methods: We conducted a retrospective, cross-sectional analysis of 112 well-characterized patients with HFE hemochromatosis and liver biopsy–validated fibrosis staging recruited between January 1, 1983, and December 31, 2013. Complete clinical, biochemical, hematologic, and noninvasive serum biochemical indices (aspartate aminotransferase to platelet ratio index [APRI] and fibrosis 4 index [FIB4]) were available. Scheuer fibrosis stages 3 and 4, APRI greater than 0.44, or FIB4 greater than 1.1 were used to define advanced hepatic fibrosis. Comparisons between groups were performed using categorical analysis, unpaired or …

Analysis Of Sars-Cov-2 Viral Loads In Stool Samples And Nasopharyngeal Swabs From Covid-19 Patients In The United Arab Emirates, Mariane Daou, Hussein Kannout, Mariam Khalili, Mohamed Almarei, Mohamed Alhashami, Zainab Alhalwachi, Fatima Alshamsi, Mohammad Tahseen Al Bataineh, Mohd Azzam Kayasseh, Abdulmajeed Al Khajeh, Shadi W. Hasan, Guan Kwang Tay, Samuel F. Feng, Dymitr Ruta, Ahmed F. Yousef, Habiba S. Alsafar, Uae Covid-19 Collaborative Partnership

Research outputs 2022 to 2026

Coronavirus disease 2019 (COVID-19) was first identified in respiratory samples and was found to commonly cause cough and pneumonia. However, non-respiratory symptoms including gastrointestinal disorders are also present and a big proportion of patients test positive for the virus in stools for a prolonged period. In this cross-sectional study, we investigated viral load trends in stools and nasopharyngeal swabs and their correlation with multiple demographic and clinical factors. The study included 211 laboratory-confirmed cases suffering from a mild form of the disease and completing their isolation period at a non-hospital center in the United Arab Emirates. Demographic and clinical information …

Sleep, Sirtuin 1 And Alzheimer’S Disease: A Review, Mehrane Mehramiz, Tenielle Porter, Simon Laws, Stephanie R. Rainey-Smith

Research outputs 2022 to 2026

Sleep plays a major role in brain health, and cognition. Disrupted sleep is a well-described symptom of Alzheimer’s disease (AD). However, accumulating evidence suggests suboptimal sleep also increases AD risk. The deacetylase Sirtuin 1 (Sirt 1), encoded by the SIRT1 gene, impacts sleep via its relationship to wake-sleep neurotransmitters and somnogens. Evidence from animal and human studies supports a significant and complex relationship between sleep, Sirt 1/ SIRT1 and AD. Numerous hypotheses attempt to explain the critical impact of Sirt 1/ SIRT1 on wake- and sleep- promoting neurons, their related mechanisms and neurotransmitters. However, there is a paucity of studies …

Dependence On A Variable Residue Limits The Breadth Of An Hiv Mper Neutralizing Antibody, Despite Convergent Evolution With Broadly Neutralizing Antibodies, Cathrine Scheepers, Prudence Kgagudi, Nonkululeko Mzindle, Elin S. Gray, Thandeka Moyo-Gwete, Bronwen E. Lambson, Brent Oosthuysen, Batsirai Mabvakure, Nigel J. Garrett, Salim S.Abdool Karim, Lynn Morris, Penny L. Moore

Research outputs 2022 to 2026

Broadly neutralizing antibodies (bNAbs) that target the membrane-proximal external region (MPER) of HIV gp41 envelope, such as 4E10, VRC42.01 and PGZL1, can neutralize > 80 % of viruses. These three MPER-directed monoclonal antibodies share germline antibody genes (IGHV1 - 69 and IGKV3 - 20) and form a bNAb epitope class. Furthermore, convergent evolution within these two lineages towards a ^111.2GW^111.3 motif in the CDRH3 is known to enhance neutralization potency. We have previously isolated an MPER neutralizing antibody, CAP206 - CH12, that uses these same germline heavy and light chain genes but lacks breadth (neutralizing only 6 % of …

Systemic Perturbations Of The Kynurenine Pathway Precede Progression To Dementia Independently Of Amyloid-Β, Marcela Cespedes, Kelly R. Jacobs, Paul Maruff, Alan Rembach, Christopher J. Fowler, Brett Trounson, Kelly K. Pertile, Rebecca L. Rumble, Stephanie R. Rainey-Smith, Christopher C. Rowe, Victor L. Villemagne, Pierrick Bourgeat, Chai K. Lim, Pratishtha Chatterjee, Ralph N. Martins, Arne Ittner, Colin L. Masters, James D. Doecke, Gilles J. Guillemin, David B. Lovejoy

Research outputs 2022 to 2026

Increasing evidence suggests that kynurenine pathway (KP) dyshomeostasis may promote disease progression in dementia. Studies in Alzheimer's disease (AD) patients confirm KP dyshomeostasis in plasma and cerebrospinal fluid (CSF) which correlates with amyloid-β and tau pathology. Herein, we performed the first comprehensive study assessing baseline levels of KP metabolites in participants enrolling in the Australian Imaging Biomarkers Flagship Study of Aging. Our purpose was to test the hypothesis that changes in KP metabolites may be biomarkers of dementia processes that are largely silent. We used a cross-sectional analytical approach to assess non-progressors (N = 73); cognitively normal (CN) or mild …

Abdominal Aortic Calcification On Lateral Spine Images Captured During Bone Density Testing And Late-Life Dementia Risk In Older Women: A Prospective Cohort Study, Tenielle Porter, Marc Sim, Richard L. Prince, John T. Schousboe, Catherine Bondonno, Wai H. Lim, Kun Zhu, Douglas P. Kiel, Jonathan M. Hodgson, Simon M. Laws, Joshua R. Lewis

Research outputs 2022 to 2026

Background: Dementia after the age of 80 years (late-life) is increasingly common due to vascular and non-vascular risk factors. Identifying individuals at higher risk of late-life dementia remains a global priority. Methods: In prospective study of 958 ambulant community-dwelling older women ( ≥ 70 years), lateral spine images (LSI) captured in 1998 (baseline) from a bone density machine were used to assess abdominal aortic calcification (AAC). AAC was classified into established categories (low, moderate and extensive). Cardiovascular risk factors and apolipoprotein E (APOE) genotyping were evaluated. Incident 14.5-year late-life dementia was identified from linked hospital and mortality records. Findings: At …

Should Acupuncture-Related Therapies Be Considered In Prediabetes Control? Results From A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Min Zhang, Carol Chunfeng Wang, Johnny Lo

Research outputs 2022 to 2026

To assess the effects and safety of acupuncture-related therapy (AT) interventions on glycemic control for prediabetes, we systematically searched 14 databases and 5 clinical registry platforms from inception to December 2020. Randomized controlled trials involving AT interventions for managing prediabetes were included (PROSPERO registration no. CRD42020209809). Of the 855 identified trials, 34 articles were included for qualitative synthesis, 31 of which were included in the final meta-analysis. Compared with usual care, sham intervention, or conventional medicine, AT treatments yielded greater reductions in the primary outcomes, including fasting plasma glucose (FPG) (standard mean difference [SMD] = -0.83; 95% confidence interval [CI], …

Visually Identified Tau 18f-Mk6240 Pet Patterns In Symptomatic Alzheimer's Disease, Natasha Krishnadas, Kun Huang, Stephanie A. Schultz, Vincent Doré, Pierrick Bourgeat, Anita M. Y. Goh, Fiona Lamb, Svetlana Bozinovski, Samantha C. Burnham, Joanne S. Robertson, Simon M. Laws, Paul Maruff, Colin L. Masters, Victor L. Villemagne, Christopher C. Rowe

Research outputs 2022 to 2026

Background: In Alzheimer's disease, heterogeneity has been observed in the postmortem distribution of tau neurofibrillary tangles. Visualizing the topography of tau in vivo may facilitate clinical trials and clinical practice. Objective: This study aimed to investigate whether tau distribution patterns that are limited to mesial temporal lobe (MTL)/limbic regions, and those that spare MTL regions, can be visually identified using 18F-MK6240, and whether these patterns are associated with different demographic and cognitive profiles. Methods : Tau 18F-MK6240 PET images of 151 amyloid-β positive participants with mild cognitive impairment (MCI) and dementia were visually rated as: tau negative, limbic predominant (LP), …

Association Of Abdominal Aortic Calcification With Peripheral Quantitative Computed Tomography Bone Measures In Older Women: The Perth Longitudinal Study Of Ageing Women, Jack Dalla Via, Marc Sim, John T. Schousboe, Douglas P. Kiel, Kun Zhu, Jonathan M. Hodgson, Abadi K. Gebre, Robin M. Daly, Richard L. Prince, Joshua R. Lewis

Research outputs 2022 to 2026

We have previously shown that abdominal aortic calcification (AAC), a marker of advanced atherosclerotic disease, is weakly associated with reduced hip areal bone mineral density (aBMD). To better understand the vascular–bone health relationship, we explored this association with other key determinants of whole-bone strength and fracture risk at peripheral skeletal sites. This study examined associations of AAC with peripheral quantitative computed tomography (pQCT)-assessed total, cortical and trabecular volumetric BMD (vBMD), bone structure and strength of the radius and tibia among 648 community-dwelling older women (mean ± SD age 79.7 ± 2.5 years). We assessed associations between cross-sectional (2003) and longitudinal …