Medicine (Western Health) - Research Publications
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ItemCarotid artery stenosis and inflammatory biomarkers: the role of inflammation-induced immunological responses affecting the vascular systems(AME PUBLISHING COMPANY, 2020-10)The death, disability and economic cost of stroke are enormous. Indeed, among the 16 million people worldwide who suffer a stroke' annually, nearly six million die, and another five million are left permanently disabled making prevention of stroke one of the most important priorities in healthcare. Currently carotid artery stenosis (CS) or narrowing of the common carotid artery (CCA) or internal carotid artery (ICA) due to atherosclerotic plaque, accounts for 20-30% of all ischemic strokes. Atherosclerosis is now regarded as a chronic inflammatory disease in response to vascular compromise especially from hypertension. This has long been known to lead to inflammation and atherosclerotic plaque formation in the blood vessels. This mini-review aims to highlight the role of inflammation and neuro-immunological processes in carotid artery disease. Various cellular elements of inflammation and advanced imaging techniques have been identified as potential markers of plaque progression. Therapies related to decreasing and modulating immune-responsive inflammation in the carotid vessels have been shown to translate into decreased occurrence of acute neurologic events and improvement of clinical outcomes.
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ItemNo Preview AvailableDetailed protocol for optimised expression and purification of functional monomeric human Heat Shock Factor 1(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2020-12)Heat Shock Factor 1 (HSF1) is the master regulator of the heat shock response, a universal survival mechanism throughout eukaryotic species used to buffer potentially lethal proteotoxic conditions. HSF1's function in vivo is regulated by several factors, including post translational modifications and elevated temperatures, whereupon it forms trimers to bind with heat shock elements in DNA. Unsurprisingly, HSF1 is also extremely sensitive to elevated temperatures in vitro, which poses specific technical challenges when producing HSF1 using a recombinant expression system. Although there are several useful publications which outline steps taken for HSF1 expression and purification, studies that describe specific strategies and detailed protocols to overcome HSF1 trimerisation and degradation are currently lacking. Herein, we have reported our detailed experimental protocol for the expression and purification of monomeric human HSF1 (HsHSF1) as a major species. We also propose a refined method of inducing HsHSF1 activation in vitro, that we consider more accurately mimics HsHSF1 activation in vivo and is therefore more physiologically relevant.
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ItemAsia-Pacific Consensus Statement on the Management of Peripheral Artery Disease: A Report from the Asian Pacific Society of Atherosclerosis and Vascular Disease Asia-Pacific Peripheral Artery Disease Consensus Statement Project Committee.(Japan Atherosclerosis Society, 2020-08-01)BACKGROUND: Peripheral artery disease (PAD) is the most underdiagnosed, underestimated and undertreated of the atherosclerotic vascular diseases despite its poor prognosis. There may be racial or contextual differences in the Asia-Pacific region as to epidemiology, availability of diagnostic and therapeutic modalities, and even patient treatment response. The Asian Pacific Society of Atherosclerosis and Vascular Diseases (APSAVD) thus coordinated the development of an Asia-Pacific Consensus Statement (APCS) on the Management of PAD. OBJECTIVES: The APSAVD aimed to accomplish the following: 1) determine the applicability of the 2016 AHA/ACC guidelines on the Management of Patients with Lower Extremity Peripheral Artery Disease to the Asia-Pacific region; 2) review Asia-Pacific literature; and 3) increase the awareness of PAD. METHODOLOGY: A Steering Committee was organized to oversee development of the APCS, appoint a Technical Working Group (TWG) and Consensus Panel (CP). The TWG appraised the relevance of the 2016 AHA/ACC PAD Guideline and proposed recommendations which were reviewed by the CP using a modified Delphi technique. RESULTS: A total of 91 recommendations were generated covering history and physical examination, diagnosis, and treatment of PAD-3 new recommendations, 31 adaptations and 57 adopted statements. This Asia-Pacific Consensus Statement on the Management of PAD constitutes the first for the Asia-Pacific Region. It is intended for use by health practitioners involved in preventing, diagnosing and treating patients with PAD and ultimately the patients and their families themselves.
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ItemHow well does the Best Guess method predict children's weight in an emergency department in 2018-2019?(WILEY, 2020-02)OBJECTIVE: For seriously ill children, weight is often required to direct critical interventions. As it is not always feasible to measure weight in emergencies, age-based weight prediction formulae may be used as an alternative. The Best Guess formulae, derived in Australia, have been shown to be among the most accurate age-based methods in Australian children. They were validated in 2010. The present study aims to re-validate the Best Guess formulae and compare their performance to the previous validation cohort. METHODS: A prospective observational study was conducted in the paediatric ED of a community teaching hospital. It included a convenience sample of children aged 1 month to 10 years who presented between July 2018 and April 2019. Seriously ill children were excluded. Data collected included measured weight, height, gender, age and ethnic group. The outcomes of interest were predictive performance of Best Guess formulae and comparison of predictive accuracy with a 2005 cohort from the same ED. RESULTS: A total of 961 patients were included; 42% girls, median age 3 years. The sample was ethnically diverse. Mean percent difference in weight was -3.3% with the formulae usually over-estimating weight. Overall, agreement within 10% was 41.8%; agreement within 20% was 72.6%. Predictive accuracy was not significantly different between the cohorts. CONCLUSION: The Best Guess method has not reduced in accuracy as a weight estimation method in emergent situations in this Australian cohort, despite a tendency to slightly over-estimate children's weight. Further study is needed to test the Best Guess method's accuracy in ethnic subgroups.
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ItemOperational challenges of international research collaborations(WILEY, 2020-02)
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ItemSarcopenia: a deserving recipient of an Australian ICD-10-AM code(WILEY, 2020-01)
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ItemChronic isolation stress is associated with increased colonic and motor symptoms in the A53T mouse model of Parkinson's disease(WILEY, 2020-03)BACKGROUND: Chronic stress exacerbates motor deficits and increases dopaminergic cell loss in several rodent models of Parkinson's disease (PD). However, little is known about effects of stress on gastrointestinal (GI) dysfunction, a common non-motor symptom of PD. We aimed to determine whether chronic stress exacerbates GI dysfunction in the A53T mouse model of PD and whether this relates to changes in α-synuclein distribution. METHODS: Chronic isolation stress was induced by single-housing WT and homozygote A53T mice between 5 and 15 months of age. GI and motor function were compared with mice that had been group-housed. KEY RESULTS: Chronic isolation stress increased plasma corticosterone and exacerbated deficits in colonic propulsion and whole-gut transit in A53T mice and also increased motor deficits. However, our results indicated that the novel environment-induced defecation response, a common method used to evaluate colorectal function, was not a useful test to measure exacerbation of GI dysfunction, most likely because of the reported reduced level of anxiety in A53T mice. A53T mice had lower corticosterone levels than WT mice under both housing conditions, but single-housing increased levels for both genotypes. Enteric neuropathy was observed in aging A53T mice and A53T mice had a greater accumulation of alpha-synuclein (αsyn) in myenteric ganglia under both housing conditions. CONCLUSIONS & INFERENCES: Chronic isolation stress exacerbates PD-associated GI dysfunction, in addition to increasing motor deficits. However, these changes in GI symptoms are not directly related to corticosterone levels, worsened enteric neuropathy, or enteric αsyn accumulation.
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ItemAssociation of periprocedural intravenous morphine use on clinical outcomes in ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention: Systematic review and meta-analysis(WILEY, 2020-07)OBJECTIVES: To conduct a systematic review and meta-analysis of studies examining the impact of periprocedural intravenous morphine on clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND: Morphine analgesia may reduce the absorption of co-prescribed P2Y12 antagonists attenuating platelet inhibition. The impact of periprocedural intravenous morphine on clinical outcomes in patients undergoing PCI for STEMI is not well defined. METHODS: Analysis of the electronic databases of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science and ClinicalTrials.gov for association of peri-PCI intravenous morphine use with in-hospital or 30-day myocardial infarction (MI) (primary outcome) and in-hospital or 30-day mortality. RESULTS: A total of 11 studies were included for systematic review. One study was a randomized controlled trial, 10 were observational studies. Five studies including 3,748 patients were included in meta-analysis of in-hospital or 30-day MI. Within this group, patients were treated concurrently with ticagrelor (n = 2,239), clopidogrel (n = 1,256) and prasugrel (n = 253). There was no significant association of in-hospital or 30-day MI with intravenous morphine (odds ratio 1.88; 95% confidence interval [CI] 0.87-4.09; I2 0%). Across seven studies and 5,800 patients, no increased risk of mortality at the same composite time endpoint was evident (odds ratio 0.70; 95% CI 0.40-1.23; I2 19%). CONCLUSIONS: Periprocedural intravenous morphine administration was not associated with adverse short-term clinical outcomes in patients undergoing primary PCI for STEMI. Further randomized trial data are needed to evaluate the pharmacologic interaction between morphine and P2Y12 antagonists with clinical outcomes.