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Sex Dimorphisms Of Aldosterone And High Salt Induced Aortic Aneurysms In Mice, Xufang Mu

Theses and Dissertations--Pharmacology and Nutritional Sciences

Aortic aneurysms, a permanent enlargement in the aorta, is a devastating disease with a high mortality rate after rupture. Aortic aneurysms exhibit strong sex dimorphisms: men are at higher risk than women while women experience worse outcomes if diagnosed. Currently, the only intervention is by open surgery or endovascular repair, and no drugs are approved for blunting the disease progression. This highlights the needs for mechanistic studies for sex-specific therapeutic targets.

Our lab established the mouse model in which mineralocorticoid receptor (MR) agonist aldosterone induces aortic aneurysms in the presence of high salt in male mice age-dependently, mimicking the aging …

Effects Of Traumatic Brain Injury On The Intestinal Tract And Gut Microbiome, Anthony Desana

Theses and Dissertations--Physiology

Traumatic brain injury (TBI) initiates not only complex neurovascular and glial changes within the brain but also pathophysiological responses that extend beyond the central nervous system. The peripheral response to TBI has become an intensive area of research, as these systemic perturbations can induce dysfunction in multiple organ systems. As there are no approved therapeutics for TBI, it is imperative that we investigate the peripheral response to TBI to identify targets for future intervention. Of particular interest is the gastrointestinal (GI) system. Even in the absence of polytrauma, brain-injured individuals are at increased risk of suffering from GI-related morbidity and …

Clinical And Biological Factors Determine Spinal Cord Injury Outcomes: Liquor To Lipids, Ethan Glaser

Theses and Dissertations--Physiology

Spinal cord injuries (SCI) are debilitating and life altering events that can lead to permanent motor and sensory loss. SCI outcomes are impacted by both clinical factors such as blood alcohol content (BAC) at the time of injury as well as biological factors like the lipid-rich myelin debris that accumulates in the injury site. Both clinical and biological factors contribute to SCI recovery, impacting neuroinflammation, locomotor recovery, and histopathology. The purpose of the studies described here is to investigate the role of acute alcohol intoxication and intracellular lipid processing pathways on SCI outcomes in a rodent model.

An elevated BAC …

Efficacy And Safety Of Vibegron For The Treatment Of Overactive Bladder In Women: A Subgroup Analysis From The Double-Blind, Randomized, Controlled Empowur Trial, Diane K. Newman Dnp, Elizabeth Thomas Ms, Heather Greene Mph, Cornelia Haag-Molkenteller Md, Susann Varano Md

Physician Associate Studies Faculty Publications

Importance The international phase 3 EMPOWUR trial demonstrated efficacy and safety of vibegron, a newer b3-adrenergic receptor agonist, in adults with overactive bladder (OAB). Women are disproportionately affected by OAB, especially those with bothersome symptoms, such as urge urinary incontinence (UUI). Objective This subgroup analysis from EMPOWUR assessed efficacy and safety of vibegron in women. Study Design In EMPOWUR, patients with OAB were randomized 5:5:4 to 12 weeks of treatment with once-daily vibegron 75 mg, placebo, or tolterodine 4-mg extended release. Efficacy end points included change from baseline at week 12 in mean daily number of micturitions, UUI episodes, and …

Covid-19 Vaccination And Alcohol Consumption: Justification Of Risks, Pavel A. Solopov

Bioelectrics Publications

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two …

Evaluation Of Cold Atmospheric Plasma For The Decontamination Of Flexible Endoscopes, R. C. Hervé, Michael G. Kong, Sudhir Bhatt, Hai-Lan Chen, E. E. Comoy, J-P. Deslys, T. J. Secker, C. W. Keevil

Bioelectrics Publications

Background: Despite adherence to standard protocols, residues including live microorganisms may remain on the various surfaces of reprocessed flexible endoscopes. Prions are infectious proteins notoriously difficult to eliminate.

Aim: We tested the potential of cold atmospheric plasma (CAP) for the decontamination of flexible endoscope various surfaces, measuring total proteins and prion-residual infectivity as an indicator of efficacy.

Methods: New PTFE endoscope channels and metal test surfaces spiked with test soil or prion-infected tissues were treated using different CAP-generating prototypes. Surfaces were then examined for the presence of residues using very sensitive fluorescence epi-microscopy. Prion residual infectivity was determined using the …

Coronary Heart Disease And Ischemic Stroke Polygenic Risk Scores And Atherosclerotic Cardiovascular Disease In A Diverse, Population-Based Cohort Study, Allison Bebo, Jamie A Jarmul, Mark J Pletcher, Natalie R Hasbani, David Couper, Vijay Nambi, Christie M Ballantyne, Myriam Fornage, Alanna C Morrison, Christy L Avery, Paul S De Vries

Faculty, Staff and Student Publications

The predictive ability of coronary heart disease (CHD) and ischemic stroke (IS) polygenic risk scores (PRS) have been evaluated individually, but whether they predict the combined outcome of atherosclerotic cardiovascular disease (ASCVD) remains insufficiently researched. It is also unclear whether associations of the CHD and IS PRS with ASCVD are independent of subclinical atherosclerosis measures. 7,286 White and 2,016 Black participants from the population-based Atherosclerosis Risk in Communities study who were free of cardiovascular disease and type 2 diabetes at baseline were included. We computed previously validated CHD and IS PRS consisting of 1,745,179 and 3,225,583 genetic variants, respectively. Cox …

Incidence And Mortality Of Conjunctival Melanoma In Australia (1982 To 2014), Aaron B. Beasley, David B. Preen, Samuel Mclenachan, Elin S. Gray, Fred K. Chen

Research outputs 2022 to 2026

Purpose: The purpose of this study was to estimate the incidence and mortality of conjunctival melanoma in Australia from 1982 to 2014. Methods: De-identified unit data for all cases of ocular melanoma were extracted from the Australian Cancer Database from 1982 to 2014. Conjunctival melanoma cases were extracted, and the incidence and mortality were analyzed. Incidence rates were age-standardized against the 2001 Australian Standard Population. Mortality was assessed using log-rank and Cox regression. Results: From 1982 to 2014, there were 299 cases of conjunctival melanoma. The age-standardized incidence rate was 0.48 (95% confidence interval [CI] = 0.41 to 0.54) per …

Tackling Dementia Together Via The Australian Dementia Network (Adnet): A Summary Of Initiatives, Progress And Plans, Sharon L. Naismith, Johannes C. Michaelian, Cherry Santos, Inga Mehrani, Joanne Robertson, Kasey Wallis, Xiaoping Lin, Stephanie A. Ward, Ralph Martins, Colin L. Masters, Michael Breakspear, Susannah Ahern, Jurgen Fripp, Peter R. Schofield, Perminder S. Sachdev, Christopher C. Rowe

Research outputs 2022 to 2026

In 2018, the Australian Dementia Network (ADNeT) was established to bring together Australia's leading dementia researchers, people with living experience and clinicians to transform research and clinical care in the field. To address dementia diagnosis, treatment, and care, ADNeT has established three core initiatives: the Clinical Quality Registry (CQR), Memory Clinics, and Screening for Trials. Collectively, the initiatives have developed an integrated clinical and research community, driving practice excellence in this field, leading to novel innovations in diagnostics, clinical care, professional development, quality and harmonization of healthcare, clinical trials, and translation of research into practice. Australia now has a national …

Multimodal Exercise In Older Patients With Advanced Pancreatic Cancer Undergoing First-Line Chemotherapy: A Case Series Examining Feasibility And Preliminary Efficacy, Hao Luo, Daniel A. Galvão, Robert U. Newton, Colin I. Tang, Nigel Spry, Dennis R. Taaffe

Research outputs 2022 to 2026

Purpose. Exercise is emerging as an adjunct therapy to cancer treatment; however, its role in older patients with advanced pancreatic cancer undergoing first-line chemotherapy is unclear. The aim of this study was to primarily provide evidence on feasibility with an exploratory examination of the initial efficacy of exercise in this clinical setting.

Materials and Methods. Six patients aged 60–75 years with de novo or recurrent advanced pancreatic cancer undergoing first-line chemotherapy consented to participate in twice-weekly exercise that included resistance and aerobic training and boxing-related activities for up to 12 weeks. Patients were monitored for attendance, adherence, and …

Consensus Guidelines For Sarcopenia Prevention, Diagnosis And Management In Australia And New Zealand, Jesse Zanker, Marc Sim, Kate Anderson, Saliu Balogun, Sharon L. Brennan-Olsen, Elsa Dent, Gustavo Duque, Christian M. Girgis, Mathis Grossmann, Alan Hayes, Tim Henwood, Vasant Hirani, Charles Inderjeeth, Sandra Iuliano, Justin Keogh, Joshua R. Lewis, Gordon S. Lynch, Julie A. Pasco, Steven Phu, Esmee M. Reijnierse, Nicholas Russell, Lara Vlietstra, Renuka Visvanathan, Troy Walker, Debra L. Waters, Solomon Yu, Andrea B. Maier, Robin M. Daly, David Scott

Research outputs 2022 to 2026

Background:

Sarcopenia is an age-associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand.

Methods:

A four-phase modified Delphi process involving topic experts and informed …

How General Practitioners And Patients Discuss Type 2 Diabetes Mellitus And Cardiovascular Diseases Concerns During Consultations: Implications For Digital Health, Urvashi Rohilla, Jayashanthi P. Ramarao, Jared Lane, Neha N. Khatri, James Smith, Kathleen Yin, Annie Y. S. Lau

Research outputs 2022 to 2026

Objective: To analyse general practitioner–patient consultations about type 2 diabetes mellitus or cardiovascular diseases and describe (i) the nature of self-management discussions; (ii) actions required from patients during and after consultation regarding self-management; and (iii) implications for digital health to support patients during (and after) consultation. Method: This study screened 281 general practitioner consultations conducted in 2017 within the UK general practice setting from an existing dataset containing videos and transcripts of consultations between GPs and patients. Secondary analysis was conducted using a multi-method approach, including descriptive, content, and visualisation analysis, to inform the nature of self-management discussions, what actions …

Prednisolone For Copd Exacerbations: Time For A Rethink, Sanjay Ramakrishnan

Research outputs 2022 to 2026

Prednisolone given universally for COPD exacerbations causes harm without any benefit. Patients deserve blood eosinophil-guided prednisolone treatment for COPD exacerbations.

Differential Dna Methylation Of Steatosis And Non-Alcoholic Fatty Liver Disease In Adolescence, Phillip E. Melton, M. A. Burton, K. A. Lillycrop, K. M. Godfrey, S. Rauschert, D. Anderson, G. C. Burdge, T. A. Mori, L. J. Beilin, O. T. Ayonrinde, J. M. Craig, John K. Olynyk, J. D. Holbrook, C. E. Pennell, W. H. Oddy, E. K. Moses, L. A. Adams, R. C. Huang

Research outputs 2022 to 2026

Background and aims:

Epigenetic modifications are associated with hepatic fat accumulation and non-alcoholic fatty liver disease (NAFLD). However, few epigenetic modifications directly implicated in such processes have been identified during adolescence, a critical developmental window where physiological changes could influence future disease trajectory. To investigate the association between DNA methylation and NAFLD in adolescence, we undertook discovery and validation of novel methylation marks, alongside replication of previously reported marks.

Approach and results:

We performed a DNA methylation epigenome-wide association study (EWAS) on DNA from whole blood from 707 Raine Study adolescents phenotyped for steatosis score and NAFLD by ultrasound at …

Plasma Aβ42/40 Ratio, P-Tau181, Gfap, And Nfl Across The Alzheimer's Disease Continuum: A Cross-Sectional And Longitudinal Study In The Aibl Cohort, Pratishtha Chatterjee, Steve Pedrini, James D. Doecke, Rohith Thota, Victor L. Villemagne, Vincent Doré, Abhay K. Singh, Penghao Wang, Stephanie Rainey-Smith, Christopher Fowler, Kevin Taddei, Hamid R. Sohrabi, Mark P. Molloy, David Ames, Paul Maruff, Christopher C. Rowe, Colin L. Masters, Ralph N. Martins, Aibl Research Group

Research outputs 2022 to 2026

Introduction:

Plasma amyloid beta (Aβ)1-42/Aβ1-40 ratio, phosphorylated-tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) are putative blood biomarkers for Alzheimer's disease (AD). However, head-to-head cross-sectional and longitudinal comparisons of the aforementioned biomarkers across the AD continuum are lacking.

Methods:

Plasma Aβ1-42, Aβ1-40, p-tau181, GFAP, and NfL were measured utilizing the Single Molecule Array (Simoa) platform and compared cross-sectionally across the AD continuum, wherein Aβ-PET (positron emission tomography)–negative cognitively unimpaired (CU Aβ−, n = 81) and mild cognitive impairment (MCI Aβ−, n = 26) participants were compared with Aβ-PET–positive participants across the AD continuum (CU Aβ+, n = …

Diagnostic Accuracy Of Autoverification And Guidance System For Covid-19 Rt-Pcr Results, Yingmu Cai, Mengyu Liu, Zhiyuan Wu, Cuihong Tian, Song Qiu, Zhen Li, Feng Xu, Wei Li, Yan Zheng, Aijuan Xu, Longxu Xie, Xuerui Tan

Research outputs 2022 to 2026

Background:

To date, most countries worldwide have declared that the pandemic of COVID-19 is over, while the WHO has not officially ended the COVID-19 pandemic, and China still insists on the personalized dynamic COVID-free policy. Large-scale nucleic acid testing in Chinese communities and the manual interpretation for SARS-CoV-2 nucleic acid detection results pose a huge challenge for labour, quality and turnaround time (TAT) requirements. To solve this specific issue while increase the efficiency and accuracy of interpretation, we created an autoverification and guidance system (AGS) that can automatically interpret and report the COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR) results relaying …

Causal Effect Of Pm1 On Morbidity Of Cause-Specific Respiratory Diseases Based On A Negative Control Exposure, Shiyun Lv, Xiangtong Liu, Zhiwei Li, Feng Lu, Moning Guo, Mengmeng Liu, Jing Wei, Zhiyuan Wu, Siqi Yu, Shihong Li, Xia Li, Wenkang Gao, Lixin Tao, Wei Wang, Jinyuan Xin, Xiuhua Guo

Research outputs 2022 to 2026

Background: Extensive studies have linked PM2.5 and PM10 with respiratory diseases (RD). However, few is known about causal association between PM1 and morbidity of RD. We aimed to assess the causal effects of PM1 on cause-specific RD. Methods: Hospital admission data were obtained for RD during 2014 and 2019 in Beijing, China. Negative control exposure and extreme gradient boosting with SHapley Additive exPlanation was used to explore the causality and contribution between PM1 and RD. Stratified analysis by gender, age, and season was conducted. Results: A total of 1,183,591 admissions for RD were recorded. Per interquartile range (28 μg/m3) uptick …

Discovery Of A Missense Mutation (Q222k) Of The Apoe Gene From The Australian Imaging, Biomarker And Lifestyle Study, Blaine R. Roberts, Scott B. Laffoon, Anne M. Roberts, Tenielle Porter, Chris Fowler, Colin L. Masters, Edward A. Dratz, Simon M. Laws

Research outputs 2022 to 2026

After age, polymorphisms of the Apolipoprotein E (APOE) gene are the biggest risk factor for the development of Alzheimer's disease (AD). During our investigation to discovery biomarkers in plasma, using 2D gel electrophoresis, we found an individual with and unusual apoE isoelectric point compared to APOE ϵ2, ϵ3, and ϵ4 carriers. Whole exome sequencing of APOE from the donor confirmed a single nucleotide polymorphism (SNP) in exon 4, translating to a rare Q222K missense mutation. The apoE ϵ4 (Q222K) mutation did not form dimers or complexes observed for apoE ϵ2 ϵ3 proteins.

Driving With Retinitis Pigmentosa, Rachael C. Heath Jeffery, Johnny Lo, Jennifer A. Thompson, Tina M. Lamey, Terri L. Mclaren, John N. Deroach, Miguel S. Kabilio, Fred K. Chen

Research outputs 2022 to 2026

Background: To establish the proportion of patients with retinitis pigmentosa (RP) meeting the Australian fitness to drive (FTD) visual standards. Methodology: A prospective consecutive case series of patients with a clinical or genetic diagnosis of RP. Data on age at symptom onset, current driving status, inheritance pattern, better eye visual acuity (BEVA), binocular Esterman visual field (BEVF) parameters, genotype and ability to meet the driving standards based on BEVA and BEVF were collected. Outcome measures included the proportion of RP patients overall meeting the standards and clinical predictors for passing. A sub-analysis was performed on those RP patients who reported …

Microvascular And Macrovascular Complications Of Type 2 Diabetes Mellitus: Exome Wide Association Analyses, Afnan Mansour, Mira Mousa, Dima Abdelmannan, Guan Tay, Ahmed Hassoun, Habiba Alsafar

Research outputs 2022 to 2026

Background: Type 2 diabetes mellitus (T2DM) is a chronic, metabolic disorder in which concomitant insulin resistance and β-cell impairment lead to hyperglycemia, influenced by genetic and environmental factors. T2DM is associated with long-term complications that have contributed to the burden of morbidity and mortality worldwide. The objective of this manuscript is to conduct an Exome-Wide Association Study (EWAS) on T2DM Emirati individuals to improve our understanding on diabetes-related complications to improve early diagnostic methods and treatment strategies. Methods: This cross-sectional study recruited 310 Emirati participants that were stratified according to their medically diagnosed diabetes-related complications: diabetic retinopathy, diabetic neuropathy, diabetic …

Impaired Muscle Function, Including Its Decline, Is Related To Greater Long-Term Late-Life Dementia Risk In Older Women, Simone Radavelli-Bagatini, Helen Macpherson, David Scott, Robin M. Daly, Jonathan M. Hodgson, Simon M. Laws, Kun Zhu, Richard L. Prince, Joshua R. Lewis, Marc Sim

Research outputs 2022 to 2026

Background: Impaired muscle function has been identified as a risk factor for declining cognitive function and cardiovascular health, both of which are risk factors for late-life dementia (after 80 years of age). We examined whether hand grip strength and timed-up-and-go (TUG) performance, including their change over 5 years, were associated with late-life dementia events in older women and whether any associations provided independent information to Apolipoprotein E ℇ4 (APOE ℇ4) genotype. Methods: Grip strength and TUG were assessed in community-dwelling older women (mean ± SD; age 75.0 ± 2.6 years) at baseline (n = 1225) and 5 years (n = …

Covid-19 In Western Australia: ‘The Last Straw’ And Hopes For A ‘New Normal’ For Parents Of Children With Long-Term Conditions, Stephanie Smith, Mary Tallon, James Smith, Lauren Jones, Evalotte Mörelius

Research outputs 2022 to 2026

Background: Children with long-term conditions are vulnerable due to the treatments required for their conditions. Since the start of the coronavirus disease 2019 (COVID-19) pandemic, Western Australians experienced restrictions that changed daily life activities but were able to return to some of their previous routines due to the restrictions. Aim: The study explored the stress experiences of parents caring for children with long-term conditions during COVID-19 in Western Australia. Design and Participants: The study was codesigned with a parent representative caring for children with long-term conditions to ensure essential questions were targeted. Twelve parents of children with various long-term conditions …

Corrigendum: Evolution, Ecology, And Zoonotic Transmission Of Betacoronaviruses: A Review, Herbert F. Jelinek, Mira Mousa, Eman Alefishat, Wael Osman, Ian Spence, Dengpan Bu, Samuel F. Feng, Jason Byrd, Paola A. Magni, Shafi Sahibzada, Guan K. Tay, Habiba S. Alsafar

Research outputs 2022 to 2026

In the published article, there was an error in the legend for Figure 1 as published. The figure legend did not indicate that it has been adapted from Plowright et al. (2017). Copyright permission was obtained from Springer Nature to adapt Figure 1 from Plowright et al. (2017). The corrected legend appears below. Figure 1. Zoonotic risk distribution, pathway to spillover, and the multimodal role of the determinants of spillover. The zoonotic risk is demonstrated by the accumulated distribution of reservoir hosts and vectors that play a role in the pathway to spillover. The risk of spillover is determined by …

It's Quite Good Fun: A Qualitative Study Of A Singing/Songwriting Programme For People With Parkinson's Disease And Their Spouses, Deborah Hersh, Shi J. Kong, Jessica Smith

Research outputs 2022 to 2026

Background: : Group singing for people with Parkinson's disease (PD) is an established intervention not only to improve voice and speech difficulties but also for emotional and social benefit. Less is known about the experiences of group singing on the couple—the person with PD and their spouse or partner together—and studies have not specifically tracked impact through time or in combination with songwriting. Aims: : To understand the impact of group singing/songwriting on couples (participants with PD and their spouses) to unpack whether this broader view might help explain why such interventions are reported as beneficial. Using a trajectory approach, …

Location Of Pathogenic Variants In Psen1 Impacts Progression Of Cognitive, Clinical, And Neurodegenerative Measures In Autosomal-Dominant Alzheimer's Disease, Stephanie A. Schultz, Zahra Shirzadi, Aaron P. Schultz, Lei Liu, Colleen D. Fitzpatrick, Eric Mcdade, Nicolas R. Barthelemy, Alan Renton, Bianca Esposito, Nelly Joseph-Mathurin, Carlos Cruchaga, Charles D. Chen, Alison Goate, Ricardo F. Allegri, Tammie L. S. Benzinger, Sarah Berman, Helena C. Chui, Anne M. Fagan, Martin R. Farlow, Nick C. Fox, Brian A. Gordon, Gregory S. Day, Neill R. Graff-Radford, Jason J. Hassenstab, Bernard J. Hanseeuw, Anna Hofmann, Clifford R. Jack Jr, Mathias Jucker, Celeste M. Karch, Robert A. Koeppe, Jae-Hong Lee, Allan I. Levey, Johannes Levin, Ralph Martins, Hiroshi Mori, John C. Morris, James Noble, Richard J. Perrin, Pedro Rosa-Neto, Stephen P. Salloway, Raquel Sanchez-Valle, Peter R. Schofield, Chengjie Xiong, Keith A. Johnson, Randall J. Bateman, Reisa A. Sperling, Jasmeer P. Chhatwal, Dominantly Inherited Alzheimer Network Investigators

Research outputs 2022 to 2026

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection …

Utility Of Dna Methylation As A Biomarker In Ageing And Alzheimer’S Disease, Lidija Milicic, Tenielle Porter, Michael Vacher, Simon M. Laws

Research outputs 2022 to 2026

Epigenetic mechanisms such as DNA methylation have been implicated in a number of diseases including cancer, heart disease, autoimmune disorders, and neurodegenerative diseases. While it is recognized that DNA methylation is tissue-specific, a limitation for many studies is the ability to sample the tissue of interest, which is why there is a need for a proxy tissue such as blood, that is reflective of the methylation state of the target tissue. In the last decade, DNA methylation has been utilized in the design of epigenetic clocks, which aim to predict an individual’s biological age based on an algorithmically defined set …

A Potential Role For Sirtuin-1 In Alzheimer's Disease: Reviewing The Biological And Environmental Evidence, Mehrane Mehramiz, Tenielle Porter, Eleanor K. O'Brien, Stephanie R. Rainey-Smith, Simon M. Laws

Research outputs 2022 to 2026

Sirtuin-1 (Sirt1), encoded by the SIRT1 gene, is a conserved Nicotinamide adenine dinucleotide (NAD+) dependent deacetylase enzyme, considered as the master regulator of metabolism in humans. Sirt1 contributes to a wide range of biological pathways via several mechanisms influenced by lifestyle, such as diet and exercise. The importance of a healthy lifestyle is of relevance to highly prevalent modern chronic diseases, such as Alzheimer's disease (AD). There is growing evidence at multiple levels for a role of Sirt1/SIRT1 in AD pathological mechanisms. As such, this review will explore the relevance of Sirt1 to AD pathological mechanisms, by describing the involvement …

Plant-Based Dietary Patterns And Parkinson's Disease: A Prospective Analysis Of The Uk Biobank, Anna Tresserra-Rimbau, Alysha S. Thompson, Nicola Bondonno, Amy Jennings, Tilman Kühn, Aedín Cassidy

Research outputs 2022 to 2026

Background: Plant-based diets have been associated with a lower risk of several chronic diseases, but the relationship with PD is unknown. Objectives: We examined the association of three different plant-based diets with PD incidence in the UK Biobank cohort. Methods: We conducted a prospective study among 126,283 participants from the UK Biobank cohort. Three plant-based diet indices (overall plant-based diet index, PDI; healthful plant-based diet index, hPDI; and unhealthful plant-based diet index, uPDI) were derived from 24-hour dietary recalls based on 17 food groups. Multivariable Cox regression models were used to estimate the risk of PD across quartiles of the …

Sixteen-Year Longitudinal Evaluation Of Blood-Based Dna Methylation Biomarkers For Early Prediction Of Alzheimer's Disease, Fernanda Schäfer Hackenhaar, Maria Josefsson, Annelie Nordin Adolfsson, Mattias Landfors, Karolina Kauppi, Tenielle Porter, Lidija Milicic, Simon M. Laws, Magnus Hultdin, Rolf Adolfsson, Sofie Degerman, Sara Pudas, Australian Imaging Biomarkers And Lifestyle Study

Research outputs 2022 to 2026

BACKGROUND: DNA methylation (DNAm), an epigenetic mark reflecting both inherited and environmental influences, has shown promise for Alzheimer's disease (AD) prediction. OBJECTIVE: Testing long-term predictive ability ( > 15 years) of existing DNAm-based epigenetic age acceleration (EAA) measures and identifying novel early blood-based DNAm AD-prediction biomarkers. METHODS: EAA measures calculated from Illumina EPIC data from blood were tested with linear mixed-effects models (LMMs) in a longitudinal case-control sample (50 late-onset AD cases; 51 matched controls) with prospective data up to 16 years before clinical onset, and post-onset follow-up. Novel DNAm biomarkers were generated with epigenome-wide LMMs, and Sparse Partial Least Squares …

Longitudinal Trajectories Of Basal Forebrain Volume In Normal Aging And Alzheimer's Disease, Ying Xia, Paul Maruff, Vincent Doré, Pierrick Bourgeat, Simon M. Laws, Christopher Fowler, Stephanie R. Rainey-Smith, Ralph N. Martins, Victor L. Villemagne, Christopher C. Rowe, Colin L. Masters, Elizabeth J. Coulson, Jurgen Fripp

Research outputs 2022 to 2026

Dysfunction of the cholinergic basal forebrain (BF) system and amyloid- (A ) deposition are early pathological features in Alzheimer's disease (AD). However, their association in early AD is not well-established. This study investigated the nature and magnitude of volume loss in the BF, over an extended period, in 516 older adults who completed A -PET and serial magnetic resonance imaging scans. Individuals were grouped at baseline according to the presence of cognitive impairment (CU, CI) and A status (A −, A +). Longitudinal volumetric changes in the BF and hippocampus were assessed across groups. The results indicated that high A …