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- Lee, Ho-Hsien, et al.
(author)
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Expression, purification and crystallization of CTB-MPR, a candidate mucosal vaccine component against HIV-1
- 2014
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In: IUCrJ. - 2052-2525. ; 1:5, s. 305-317
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Journal article (peer-reviewed)abstract
- CTB-MPR is a fusion protein between the B subunit of cholera toxin (CTB) andthe membrane-proximal region of gp41 (MPR), the transmembrane envelopeprotein ofHuman immunodeficiency virus 1(HIV-1), and has previously beenshown to induce the production of anti-HIV-1 antibodies with antiviralfunctions. To further improve the design of this candidate vaccine, X-raycrystallography experiments were performed to obtain structural informationabout this fusion protein. Several variants of CTB-MPR were designed,constructed and recombinantly expressed inEscherichia coli. The first variantcontained a flexible GPGP linker between CTB and MPR, and yielded crystalsthat diffracted to a resolution of 2.3 A ̊, but only the CTB region was detectedin the electron-density map. A second variant, in which the CTB was directlyattached to MPR, was shown to destabilize pentamer formation. A thirdconstruct containing a polyalanine linker between CTB and MPR proved tostabilize the pentameric form of the protein during purification. The purificationprocedure was shown to produce a homogeneously pure and monodispersesample for crystallization. Initial crystallization experiments led to pseudo-crystals which were ordered in only two dimensions and were disordered inthe third dimension. Nanocrystals obtained using the same precipitant showedpromising X-ray diffraction to 5 A ̊resolution in femtosecond nanocrystallo-graphy experiments at the Linac Coherent Light Source at the SLAC NationalAccelerator Laboratory. The results demonstrate the utility of femtosecondX-ray crystallography to enable structural analysis based on nano/microcrystalsof a protein for which no macroscopic crystals ordered in three dimensions havebeen observed before.
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- Stewart Williams, Jennifer A, et al.
(author)
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Assessing patterns of use of cardio-protective polypill component medicines in Australian women
- 2013
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In: Drugs & Aging. - : Springer. - 1170-229X .- 1179-1969. ; 30:3, s. 193-203
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Journal article (peer-reviewed)abstract
- BACKGROUND: A low-cost 'polypill' could theoretically be one way of improving medication affordability and compliance for secondary prevention of cardiovascular and cerebrovascular disease. The polypill has also been proposed as a primary prevention strategy. Yet many of the issues surrounding the polypill are still being debated and the underlying assumptions have not been proven. In this paper, we step back from the complexities of the debate and report upon the utilization of polypill component medicines in two population cohorts of Australian women who were aged 56-61 years and 81-86 years in 2007.OBJECTIVES: The aims of this study were firstly, to describe the association between the women's characteristics (health, illness, behavioural, demographic, socioeconomic) and their use of statins and antihypertensive medicines for the treatment of heart disease, and secondly, to discuss possible health and economic benefits for women with these characteristics that may be expected to result from the introduction of a cardio-protective polypill.METHODS: Survey records from the Australian Longitudinal Study on Women's Health (ALSWH) were linked to 2007 Pharmaceutical Benefits Scheme (PBS) claims for 7,116 mid-aged women and 4,526 older-aged women. Associations between women's characteristics (self-reported in ALSWH surveys) and their use of statins and antihypertensive medicines (measured through PBS claims in 2007) were analysed using Chi-square and multivariate regression techniques.RESULTS: Between 2002 and 2007, the use of statins in combination with antihypertensives by mid- and older-aged Australian women increased. A moderate yet increasing proportion of mid-aged women were taking statins without antihypertensives, and a high proportion of older-aged women were using antihypertensives without statins. A high proportion of women who were prescribed both statins and antihypertensives were in lower socioeconomic groups and reported difficulty managing on their incomes.CONCLUSION: These results suggest that a polypill may provide an easy-to-take, cheaper alternative for Australian women already taking multiple cardiovascular disease medications, with particular benefits for older women and women in lower socioeconomic groups. Future research is needed to quantify the potential social and economic benefits of the polypill.
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- Stewart Williams, Jennifer, et al.
(author)
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Identification of higher hospital costs and more frequent admissions among mid-aged Australian women who self-report diabetes mellitus
- 2016
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In: Maturitas. - : Elsevier. - 0378-5122 .- 1873-4111. ; 90, s. 58-63
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Journal article (peer-reviewed)abstract
- Objective: To ascertain whether the hospital costs for mid-aged Australian women who self-reported diabetes mellitus (DM) and who had one or more hospital admission during an eight and a half year period were higher than the hospital costs for other similarly aged non-DM women. Methods: The sample comprised 2,392 mid-aged women, resident in New South Wales (NSW) Australia and participating in the Australian Longitudinal Study on Women’s Health (ALSWH), who had any NSW hospital admissions during the eight and a half year period 1 July 2000 to 31 December 2008. Analyses were conducted on linked data from ALSWH surveys and the NSW Admitted Patient Data Collection (APDC). Hospital costs were compared for the DM and non-DM cohorts of women. A generalized linear model measured the association between hospital costs and self-reported DM. Results: Eight and a half year hospital costs were 41% higher for women who self-reported DM in the ALSWH surveys (p < 0.0001). On average, women who self-reported DM had significantly (p < 0.0001) more hospital admissions (5.3) than women with no reported DM (3.4). The average hospital stay per admission was not significantly different between the two groups of women. Conclusions: Self-reported DM status in mid-aged Australian women is a predictor of higher hospital costs. This simple measure can be a useful indicator for public policy makers planning early-stage interventions that target people in the population at risk of DM.
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- Jiang, Heng, et al.
(author)
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Beyond the Drinker : Alcohol's Hidden Costs in 2016 in Australia
- 2022
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In: Journal of Studies on Alcohol and Drugs. - : Alcohol Research Documentation, Inc.. - 1937-1888 .- 1938-4114. ; 83:4, s. 512-524
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Journal article (peer-reviewed)abstract
- Objective: Drawing on a study of the range and mag-nitude of harms that alcohol caused to specific others in Australia, and on social and health agency statistics for collective costs, this article produces an analysis of the economic cost of alcohol's harm to others (AHTO) in Australia. Method: This study used a general population survey and routinely collected social response agencies' data to quantify different costs of AHTO, using methods consistent with International Guidelines for Estimating the Costs of Substance Abuse. This approach estimates costs for health care and social services, crime costs, costs of productivity loss, quality of life-year loss and other expenses, including both tangible costs (direct and indirect) and intangible costs of loss of quality of life (respondents' self-reported loss of health-related quality of life). Results: The cost of AHTO in Australia was AUD$19.81 bil-lion (95% CI [11.99, 28.34]), with tangible costs accounting for 58% of total costs ($11.45 billion, which is 0.68% of gross domestic product in 2016) and intangible costs of $8.36 billion. The costs to private individu-als or households ($18.1 billion and 89% of total costs of AHTO) are greater than the costs to the government or society because of others' drinking in Australia. Conclusions: This study presents an estimation of the economic cost of harm from others' drinking. The economic costs from others' drinking are large and of much the same magnitude as the costs that drinkers impose on themselves, as found in previous studies. Preventing harm to others from drinking is important as a public health goal for both economic and humane reasons.
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