Publications by authors named "Kate Smith"

125 Publications

Factors associated with the increased risk of dementia found in the Torres Strait.

Australas J Ageing 2021 Aug 5. Epub 2021 Aug 5.

College of Medicine and Dentistry, James Cook University, Cairns, QLD, Australia.

Objective: To identify the specific risk factors for dementia in the Torres Strait.

Methods: This research was conducted as part of a cross-sectional dementia prevalence study conducted in the Torres Strait. Participants underwent a comprehensive health assessment, where data on risk factors were collected, and a Geriatrician assessment, which was used to establish dementia diagnoses.

Results: A total of 276 Torres Strait residents aged between 45 and 93 participated in the study. Cerebrovascular disease, chronic kidney disease and older age were the most significant risk factors in this population. Once adjusted for age, cerebrovascular disease, chronic kidney disease, diabetes, low education and problems with mobility and incontinence were significantly associated with dementia.

Conclusions: Reducing dementia risk in the Torres Strait requires multifactorial interventions to address potentially modifiable risk factors with a particular focus on addressing the development of chronic midlife diseases.
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http://dx.doi.org/10.1111/ajag.12980DOI Listing
August 2021

Global Prevalence of Young-Onset Dementia: A Systematic Review and Meta-analysis.

JAMA Neurol 2021 Sep;78(9):1080-1090

Western Australian Centre for Health and Aging, University of Western Australia, Perth, Australia.

Importance: Reliable prevalence estimates are lacking for young-onset dementia (YOD), in which symptoms of dementia start before the age of 65 years. Such estimates are needed for policy makers to organize appropriate health care.

Objective: To determine the global prevalence of YOD.

Data Sources: The PubMed, Embase, CINAHL, and PsycInfo databases were systematically searched for population-based studies on the prevalence of YOD published between January 1, 1990, and March 31, 2020.

Study Selection: Studies containing data on the prevalence of dementia in individuals younger than 65 years were screened by 2 researchers for inclusion in a systematic review and meta-analysis.

Data Extraction And Synthesis: Prevalence estimates on 5-year age bands, from 30 to 34 years to 60 to 64 years, were extracted. Random-effects meta-analyses were conducted to pool prevalence estimates. Results were age standardized for the World Standard Population. Heterogeneity was assessed by subgroup analyses for sex, dementia subtype, study design, and economic status based on the World Bank classification and by meta-regression.

Main Outcomes And Measures: Prevalence estimates of YOD for 5-year age bands.

Results: A total of 95 unique studies were included in this systematic review, of which 74 with 2 760 379 unique patients were also included in 5-year age band meta-analyses. Studies were mostly conducted in Europe and in older groups in Asia, North America, and Oceania. Age-standardized prevalence estimates increased from 1.1 per 100 000 population in the group aged 30 to 34 years to 77.4 per 100 000 population in the group aged 60 to 64 years. This gives an overall global age-standardized prevalence of 119.0 per 100 000 population in the age range of 30 to 64 years, corresponding to 3.9 million people aged 30 to 64 years living with YOD in the world. Subgroup analyses showed prevalence between men and women to be similar (crude estimates for men, 216.5 per 100 000 population; for women, 293.1 per 100 000 population), whereas prevalence was lower in high-income countries (crude estimate, 663.9 per 100 000 population) compared with upper-middle-income (crude estimate, 1873.6 per 100 000 population) and lower-middle-income (crude estimate, 764.2 per 100 000 population) countries. Meta-regression showed that age range (P < .001), sample size (P < .001), and study methodology (P = .02) significantly influenced heterogeneity between studies.

Conclusions And Relevance: This systematic review and meta-analysis found an age-standardized prevalence of YOD of 119.0 per 100 000 population, although estimates of the prevalence in low-income countries and younger age ranges remain scarce. These results should help policy makers organize sufficient health care for this subgroup of individuals with dementia.

Study Registration: PROSPERO CRD42019119288.
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http://dx.doi.org/10.1001/jamaneurol.2021.2161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290331PMC
September 2021

Strong Carers, Strong Communities: a cluster randomised controlled trial to improve wellbeing of family carers of older people in remote Aboriginal communities.

Rural Remote Health 2021 07 14;21(3):6078. Epub 2021 Jul 14.

Centre for Aboriginal Medical and Dental Health, University of Western Australia, Perth, Australia

Introduction: Unpaid carers have a crucial role in supporting older people with cognitive impairment and disability, but their own health and wellbeing are often impacted. There are limited data on how carer strain, depression and empowerment may be improved for carers.

Methods: This was a cluster randomised controlled trial to compare the effect of a carer support program developed with a community-based participatory action research (PAR) approach to the delivery of information sessions to 100 carers of people aged 45 years or more living in four remote Aboriginal communities in Western Australia.

Results: The mean age of carers was 38.3±14.9 years, 76% were female and 77% were children or grandchildren of the care recipient. Carer strain and empowerment measures did not change significantly between baseline and follow-up. A statistically significant decrease in depression scores was observed in the PAR group. However, decreases were observed in both the PAR and control groups, and the change in scores did not differ significantly between groups. Depression scores decreased most in those who had not attended high school. Overall, the proportion of participants meeting criteria for depression decreased from 18.8% at baseline to 8.3% at follow-up.

Conclusion: A carer support program was of equivocal benefit, although this research demonstrates that the wellbeing of carers in remote Aboriginal communities can potentially be markedly improved by outreach strategies.
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http://dx.doi.org/10.22605/RRH6078DOI Listing
July 2021

Machine-assessed tar yield marketing on cigarette packages from two cities in South Korea.

Tob Induc Dis 2021 25;19:54. Epub 2021 Jun 25.

Institute for Global Tobacco Control, Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of Public Health, Baltimore, United States.

Introduction: South Koreans continue to smoke at high rates. Tobacco manufacturers have a history of branding cigarettes with misleading descriptors including the introduction of low or ultra-low tar brand variants. The government bans traditional misleading descriptors (low, mild) but requires the presence of machine-assessed tar yields on cigarette packages. Literature suggests the presence of quantitative constituents can be misleading for smokers. We analyzed the machine-assessed tar value branding and the presence of additional branding that highlight tar levels on South Korean cigarette packs.

Methods: In August 2018, we analyzed 178 unique cigarette packs purchased in Seoul and Busan, South Korea using a systematic protocol. Cigarette packs were coded for tar levels and classified as ultra-low, low, mid, and high tar. The presence of misleading descriptors and any additional branding relating to tar or potentially indicating strength were also coded.

Results: Machine-assessed tar yields ranged from 0.1 to 8 mg. Cigarettes with a 1 mg machine-assessed tar yield accounted for 38% of all packs purchased. A majority (80%) of packs with tar values <3 mg had additional marketing present on the pack that highlighted tar yields, compared to 45% for packs with tar values 3 mg or greater. Many (85%) of the 1 mg packs and all of the 0.1 and 0.5 mg packs had additional marketing present that referenced tar levels.

Conclusions: These findings suggest that tobacco manufacturers are highlighting and reinforcing the tar yields of lower tar cigarettes by the deliberate use of tar level branding. These actions have the potential to mislead South Korean consumers that some cigarettes are less harmful than others. Strengthening of tobacco packaging regulations to prohibit references to tar yields on packs are needed to further protect consumers.
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http://dx.doi.org/10.18332/tid/136421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231860PMC
June 2021

Preparing for a pandemic: spending dynamics and panic buying during the COVID-19 first wave.

Fisc Stud 2021 Jun 8;42(2):249-264. Epub 2021 Jun 8.

Institute for Fiscal Studies; University College London.

In times of heightened uncertainty, consumers face incentives to build up precautionary stocks of essential supplies. We study consumer spending dynamics during one such time, the first infection wave of the COVID-19 pandemic, using household scanner data covering fast-moving consumer goods in the United Kingdom. We document large increases in demand for storable products, such as food staples and household supplies, in the days before lockdown. Households in all socio-economic groups exhibit unusually high demand pre-lockdown, but there is a clear gradient, with the largest demand spikes for wealthier households. Although stories of people purchasing extreme amounts received a lot of attention, higher aggregate demand was mainly driven by more households than usual choosing to buy storable products, with only small increases in average quantities bought on a given trip. Temporary limits on the number of units per transaction, introduced following the demand spike, are therefore unlikely to lead to the avoidance of stock-outs.
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http://dx.doi.org/10.1111/1475-5890.12271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209877PMC
June 2021

Alzheimer's disease research progress in Australia: The Alzheimer's Association International Conference Satellite Symposium in Sydney.

Alzheimers Dement 2021 May 31. Epub 2021 May 31.

Departments of Neuroscience and Neurology, Center for Translational Research in Neurodegenerative Disease, Normal Fixel Center for Neurological Diseases, University of Florida College of Medicine, Gainesville, Florida, USA.

The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.
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http://dx.doi.org/10.1002/alz.12380DOI Listing
May 2021

Environmental hygiene, knowledge and cleaning practice: a phenomenological study of nurses and midwives during COVID-19.

Am J Infect Control 2021 09 26;49(9):1123-1128. Epub 2021 Apr 26.

School of Nursing and Midwifery, University of Newcastle, Ourimbah, New South Wales, Australia; School of Nursing, Avondale College of Higher Education, Wahroonga, New South Wales, Australia. Electronic address:

Background: Environmental cleanliness is a fundamental tenet in nursing and midwifery but often overshadowed in practice. This study explored nurses' and midwives' knowledge and experiences of infection prevention and control (IPC) processes and cleaning, and perceptions about workplace risk-management during COVID-19.

Methods: Six registered and enrolled nurses (one with dual midwife qualifications) were recruited. In-depth telephone interviews were analyzed using Colaizzi's phenomenological method.

Results: Four major themes were identified: Striving towards environmental cleanliness; Knowledge and learning feeds good practice; There's always doubt in the back of your mind; and COVID has cracked it wide open. These articulate the nurses' and midwives' experiences and knowledge of IPC, particularly during COVID-19.

Discussion: The findings emphasize the dynamic, interdependent nature of clinical (time, staff knowledge and compliance, work processes, hospital design) and organizational contexts and environmental cleanliness, which must be constantly maintained. COVID-19 opened up critical insights regarding poor past practices and lack of IPC compliance.

Conclusions: COVID-19 has highlighted the criticality of environmental cleanliness within clinical and community settings. Evidence-based, experiential learning is important for nurses and midwives at all career stages, but provides only one solution. Clinician-led hospital design may also reduce the spread of infection; thus, promoting better patient care.
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http://dx.doi.org/10.1016/j.ajic.2021.04.080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074523PMC
September 2021

REPEAT SPILLOVER OF BEAK AND FEATHER DISEASE VIRUS INTO AN ENDANGERED PARROT HIGHLIGHTS THE RISK ASSOCIATED WITH ENDEMIC PATHOGEN LOSS IN ENDANGERED SPECIES.

J Wildl Dis 2020 10;56(4):896-906

School of Animal and Veterinary Sciences, Charles Sturt University, Boorooma Street, Wagga Wagga, New South Wales, 2650, Australia.

Conservation efforts for the orange-bellied parrot (Neophema chrysogaster), one of the world's most critically endangered bird species, have been hampered by beak and feather disease virus (BFDV) spillover infection. To understand the vulnerability of orange-bellied parrots to potential reservoirs of infection we investigated geographic versus taxonomic structure in 160 full-genome and 319 partial Rep gene BFDV sequences from captive and wild orange-bellied parrots and other wild parrot species in Australia. We found that Australian BFDV populations are structured by host taxonomy. By identifying genetic stratification of BFDV in reservoir hosts we characterized three separate recent incursions of BFDV into orange-bellied parrots from other wild parrots, which demonstrates the susceptibility of critically endangered species to multiple threats of pathogen re-emergence. Our study highlighted how loss of endemic circulating BFDV in orange-bellied parrots precipitated repeated spillover into an immunologically naïve population, causing significant disease.
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http://dx.doi.org/10.7589/2018-06-154DOI Listing
October 2020

Application of Uniform Manifold Approximation and Projection (UMAP) in spectral imaging of artworks.

Spectrochim Acta A Mol Biomol Spectrosc 2021 May 4;252:119547. Epub 2021 Feb 4.

Northwestern University / Art Institute of Chicago Center for Scientific Studies in the Arts (NU-ACCESS), 2145 Sheridan Road, Evanston, IL, United States. Electronic address:

This study assesses the potential of Uniform Manifold Approximation and Projection (UMAP) as an alternative tool to t-distributed Stochastic Neighbor Embedding (t-SNE) for the reduction and visualization of visible spectral images of works of art. We investigate the influence of UMAP parameters-such as, correlation distance, minimum embedding distance, as well as number of embedding neighbors- on the reduction and visualization of spectral images collected from Poèmes Barbares (1896), a major work by the French artist Paul Gauguin in the collection of the Harvard Art Museums. The use of a cosine distance metric and number of neighbors equal to 10 preserves both the local and global structure of the Gauguin dataset in a reduced two-dimensional embedding space thus yielding simple and clear groupings of the pigments used by the artist. The centroids of these groups were identified by locating the densest regions within the UMAP embedding through a 2D histogram peak finding algorithm. These centroids were subsequently fit to the dataset by non-negative least square thus forming maps of pigments distributed across the work of art studied. All findings were correlated to macro XRF imaging analyses carried out on the same painting. The described procedure for reduction and visualization of spectral images of a work of art is quick, easy to implement, and the software is opensource thus promising an improved strategy for interrogating reflectance images from complex works of art.
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http://dx.doi.org/10.1016/j.saa.2021.119547DOI Listing
May 2021

Regional and global perspectives of honey as a record of lead in the environment.

Environ Res 2021 04 30;195:110800. Epub 2021 Jan 30.

Analytical, Environmental and Geochemistry, Vrije Universiteit Brussel, Brussels, Belgium.

Honey from Apis mellifera is a useful and inexpensive biomonitor for mapping metal distributions in urban centers. The sampling resolution of a biomonitoring survey (e.g., city versus global scale) determines which geochemical processes are reflected in the results. This study presents Pb isotopic compositions and metal concentrations in honey from around the world, sampled at varying resolutions: honey from Canada (n = 21), the United States (n = 111), Belgium (n = 25), and New Zealand (n = 10), with additional samples from Afghanistan, Brazil, Cuba, Germany, Liberia, Taiwan, and Turkey. Honey was sampled at high resolution in two uniquely different land-use settings (New York Metro Area and the Hawaiian island of Kaua'i), at regional-scale resolution in eastern North America (including the Great Lakes region), and Pb isotopic compositions of all samples were compared on a global scale. At high sampling resolution, metal concentrations in honey reveal spatially significant concentration gradients: in New York City, metals associated with human activity and city infrastructure (e.g., Pb, Sb, Ti, V) are more concentrated in honey collected within the city compared to honey from upstate New York, and metal concentrations in honey from Kaua'i suggest polluting effects of nearby agricultural operations. At lower resolution (regional and global scales), lead isotopic compositions of honey are more useful than metal concentrations in revealing large-scale Pb processes (e.g., the enduring legacy of global leaded gasoline use throughout the twentieth century) and the continental origin of the honey. Lead isotopic compositions of honey collected from N. America (especially from the eastern USA) are more radiogenic (Pb/Pb: 1.132-1.253, Pb/Pb: 2.001-2.129) compared to European honey, and honey from New Zealand, which has the least radiogenic isotopic compositions measured in this study (Pb/Pb: 1.077-1.160, Pb/Pb: 2.090-2.187). Thus, biomonitoring using honey at different resolutions reflects differing processes and, to some extent, a honey terroir defined by the Pb isotopic composition. The data presented here provide important (and current) global context for future studies that utilize Pb isotopes in honey. Moreover, this study exhibits community science in action, as most of the honey was collected by collaborators around the world, working directly with local apiarists and hobby beekeepers.
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http://dx.doi.org/10.1016/j.envres.2021.110800DOI Listing
April 2021

Self-reported health and older Aboriginal Australians - healing, balance, connection, and inner spirit are important learnings for all of us.

Int Psychogeriatr 2020 11;32(11):1267-1270

WA Centre for Health and Ageing, University of Western Australia, Perth, Australia.

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http://dx.doi.org/10.1017/S1041610219002230DOI Listing
November 2020

Prevalence of dementia in the Torres Strait.

Australas J Ageing 2021 Jun 10;40(2):e125-e132. Epub 2020 Nov 10.

College of Medicine and Dentistry, James Cook University, Cairns, Queensland, Australia.

Objective: To examine the prevalence of dementia and problems associated with ageing in the Torres Strait.

Methods: The study was conducted across all 18 island and 5 mainland communities in the Torres Strait and Northern Peninsula Area of Far North Queensland. Participants underwent a comprehensive health assessment and a Geriatrician assessment, which were used to establish consensus diagnoses.

Results: A total of 276 Torres Strait residents aged between 45 and 93 participated in the study. The prevalence of dementia in the sample was 14.2%, which was 2.87 times higher than the wider Australian population.

Conclusion: Torres Strait Islander peoples share the increased risk of dementia seen in Aboriginal Australians compared to the wider community. This highlights the need for interventions to address this increased dementia risk for Aboriginal and Torres Strait Islander communities.
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http://dx.doi.org/10.1111/ajag.12878DOI Listing
June 2021

Lysozyme conformational changes with ionic liquids: Spectroscopic, small angle x-ray scattering and crystallographic study.

J Colloid Interface Sci 2021 Mar 13;585:433-443. Epub 2020 Oct 13.

School of Science, College of Science, Engineering and Health, RMIT University, 124 La Trobe Street, Melbourne, VIC 3000, Australia. Electronic address:

Solvents that support protein functionality are important for biochemical applications, and new solvents are required. Here we employ FTIR and fluorescence spectroscopies, small angle X-ray scattering (SAXS) and X-ray crystallography to understand conformational changes of lysozyme with ionic liquids (ILs) added. Spectroscopic techniques identified that the secondary structure of lysozyme was maintained at the lower IL concentrations of 1 and 5 mol%, though the Tryptophan environment was significantly altered with nitrate-based ILs present. SAXS experiments indicated that the radius of gyration of lysozyme increased with 1 mol% IL present, and then decreased with increasing IL concentrations. The tertiary structure, particularly the loop regions, changed as a function of IL concentration, and this depended on the IL type. The crystallographic structure of lysozyme with the IL of ethylammonium nitrate present confirmed the loop region was extended, and identified three specific binding sites with nitrate ions, and that the positively charged areas were IL sensitive regions. This work provides a detailed understanding of lysozyme conformational changes in the presence of ILs. This approach can be extended to other functionally-important proteins.
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http://dx.doi.org/10.1016/j.jcis.2020.10.024DOI Listing
March 2021

The potential health impact of restricting less-healthy food and beverage advertising on UK television between 05.30 and 21.00 hours: A modelling study.

PLoS Med 2020 10 13;17(10):e1003212. Epub 2020 Oct 13.

Centre on Population Approaches for Non-Communicable Disease Prevention, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.

Background: Restrictions on the advertising of less-healthy foods and beverages is seen as one measure to tackle childhood obesity and is under active consideration by the UK government. Whilst evidence increasingly links this advertising to excess calorie intake, understanding of the potential impact of advertising restrictions on population health is limited.

Methods And Findings: We used a proportional multi-state life table model to estimate the health impact of prohibiting the advertising of food and beverages high in fat, sugar, and salt (HFSS) from 05.30 hours to 21.00 hours (5:30 AM to 9:00 PM) on television in the UK. We used the following data to parameterise the model: children's exposure to HFSS advertising from AC Nielsen and Broadcasters' Audience Research Board (2015); effect of less-healthy food advertising on acute caloric intake in children from a published meta-analysis; population numbers and all-cause mortality rates from the Human Mortality Database for the UK (2015); body mass index distribution from the Health Survey for England (2016); disability weights for estimating disability-adjusted life years (DALYs) from the Global Burden of Disease Study; and healthcare costs from NHS England programme budgeting data. The main outcome measures were change in the percentage of the children (aged 5-17 years) with obesity defined using the International Obesity Task Force cut-points, and change in health status (DALYs). Monte Carlo analyses was used to estimate 95% uncertainty intervals (UIs). We estimate that if all HFSS advertising between 05.30 hours and 21.00 hours was withdrawn, UK children (n = 13,729,000), would see on average 1.5 fewer HFSS adverts per day and decrease caloric intake by 9.1 kcal (95% UI 0.5-17.7 kcal), which would reduce the number of children (aged 5-17 years) with obesity by 4.6% (95% UI 1.4%-9.5%) and with overweight (including obesity) by 3.6% (95% UI 1.1%-7.4%) This is equivalent to 40,000 (95% UI 12,000-81,000) fewer UK children with obesity, and 120,000 (95% UI 34,000-240,000) fewer with overweight. For children alive in 2015 (n = 13,729,000), this would avert 240,000 (95% UI 65,000-530,000) DALYs across their lifetime (i.e., followed from 2015 through to death), and result in a health-related net monetary benefit of £7.4 billion (95% UI £2.0 billion-£16 billion) to society. Under a scenario where all HFSS advertising is displaced to after 21.00 hours, rather than withdrawn, we estimate that the benefits would be reduced by around two-thirds. This is a modelling study and subject to uncertainty; we cannot fully and accurately account for all of the factors that would affect the impact of this policy if implemented. Whilst randomised trials show that children exposed to less-healthy food advertising consume more calories, there is uncertainty about the nature of the dose-response relationship between HFSS advertising and calorie intake.

Conclusions: Our results show that HFSS television advertising restrictions between 05.30 hours and 21.00 hours in the UK could make a meaningful contribution to reducing childhood obesity. We estimate that the impact on childhood obesity of this policy may be reduced by around two-thirds if adverts are displaced to after 21.00 hours rather than being withdrawn.
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http://dx.doi.org/10.1371/journal.pmed.1003212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553286PMC
October 2020

Regulation of ALT-associated homology-directed repair by polyADP-ribosylation.

Nat Struct Mol Biol 2020 12 12;27(12):1152-1164. Epub 2020 Oct 12.

Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.

The synthesis of poly(ADP-ribose) (PAR) reconfigures the local chromatin environment and recruits DNA-repair complexes to damaged chromatin. PAR degradation by poly(ADP-ribose) glycohydrolase (PARG) is essential for progression and completion of DNA repair. Here, we show that inhibition of PARG disrupts homology-directed repair (HDR) mechanisms that underpin alternative lengthening of telomeres (ALT). Proteomic analyses uncover a new role for poly(ADP-ribosyl)ation (PARylation) in regulating the chromatin-assembly factor HIRA in ALT cancer cells. We show that HIRA is enriched at telomeres during the G2 phase and is required for histone H3.3 deposition and telomere DNA synthesis. Depletion of HIRA elicits systemic death of ALT cancer cells that is mitigated by re-expression of ATRX, a protein that is frequently inactivated in ALT tumors. We propose that PARylation enables HIRA to fulfill its essential role in the adaptive response to ATRX deficiency that pervades ALT cancers.
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http://dx.doi.org/10.1038/s41594-020-0512-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809635PMC
December 2020

Tendon paratenon involvement in patients with gout: An under-recognized ultrasound feature of tendinous gout?

Joint Bone Spine 2021 01 16;88(1):105051. Epub 2020 Jul 16.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, LS7 4SA Leeds, United Kingdom; Polytechnic University of Marche, Rheumatology Unit, Department of Clinical and Molecular Sciences, "Carlo Urbani" Hospital, Jesi, Ancona, Italy.

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http://dx.doi.org/10.1016/j.jbspin.2020.07.001DOI Listing
January 2021

Crystal structure of posnjakite formed in the first crystal water-cooling line of the ANSTO Melbourne Australian Synchrotron MX1 Double Crystal Monochromator.

Acta Crystallogr E Crystallogr Commun 2020 Jul 26;76(Pt 7):1136-1138. Epub 2020 Jun 26.

Australian Synchrotron, ANSTO - Melbourne, 800 Blackburn Rd, Clayton, VIC, 3168, Australia.

Exceptionally large crystals of posnjakite, CuSO(OH)(HO), formed during corrosion of a Swagelock(tm) Snubber copper gasket within the MX1 beamline at the ANSTO-Melbourne, Australian Synchrotron. The crystal structure was solved using synchrotron radiation to = 0.029 and revealed a structure based upon [Cu(OH)(HO)O] sheets, which contain Jahn-Teller-distorted Cu octa-hedra. The sulfate tetra-hedra are bonded to one side of the sheet corner sharing and linked to successive sheets extensive hydrogen bonds. The sulfate tetra-hedra are split and rotated, which enables additional hydrogen bonds.
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http://dx.doi.org/10.1107/S2056989020008099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336798PMC
July 2020

Evaluating Spatiotemporal Resolution of Trace Element Concentrations and Pb Isotopic Compositions of Honeybees and Hive Products as Biomonitors for Urban Metal Distribution.

Geohealth 2020 Jul 1;4(7):e2020GH000264. Epub 2020 Jul 1.

Pacific Centre for Isotopic and Geochemical Research, Department of Earth, Ocean and Atmospheric Sciences University of British Columbia Vancouver British Columbia Canada.

Assessing metal distributions in cities is an important aspect of urban environmental quality management. Western honeybees () and their products are biomonitors that can elucidate small-scale metal distribution within a city. We compare range and variations in trace element (TE) concentrations and lead (Pb) isotopic compositions of honey, bee tissue, bee pollen, and propolis collected throughout Metro Vancouver (BC, Canada). Honey, bee, and bee pollen results have similar TE and isotopic trends; samples collected in urban and industrialized areas exhibit elevated concentrations of anthropogenically influenced TE (e.g., Pb, Zn, V, and Ti) and a less radiogenic Pb isotopic composition (i.e., lower Pb/Pb and elevated Pb/Pb) relative to their suburban and rural counterparts. For example, Pb/Pb, Pb/Pb in honey range from 1.126, 2.131 and 1.184, 2.063; extremes measured in honey from urban and suburban/rural areas, respectively. Except for propolis, measured and interpolated (kriged) results in all materials reflect the immediate zoning or land use setting near the hive, providing kilometer-scale geospatial resolution, suitable for monitoring urban systems. Statistical analysis reveals that no systematic variations or intra- or inter-annual trends exist in TE concentrations or Pb isotopic compositions, including among sampling and field methods (i.e., old vs. new hive equipment and honey from the brood nest box vs. honey super). The results of this systematic study using honeybees and hive products in Metro Vancouver provide a robust, current baseline for future comparison of local land use and environmental policy change.
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http://dx.doi.org/10.1029/2020GH000264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340846PMC
July 2020

Targeting Nuclear LSD1 to Reprogram Cancer Cells and Reinvigorate Exhausted T Cells via a Novel LSD1-EOMES Switch.

Front Immunol 2020 16;11:1228. Epub 2020 Jun 16.

Gene Regulation and Translational Medicine Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

Lysine specific demethylase 1 (LSD1) is a key epigenetic eraser enzyme implicated in cancer metastases and recurrence. Nuclear LSD1 phosphorylated at serine 111 (nLSD1p) has been shown to be critical for the development of breast cancer stem cells. Here we show that circulating tumor cells isolated from immunotherapy-resistant metastatic melanoma patients express higher levels of nLSD1p compared to responders, which is associated with co-expression of stem-like, mesenchymal genes. Targeting nLSD1p with selective nLSD1 inhibitors better inhibits the stem-like mesenchymal signature than traditional FAD-specific LSD1 catalytic inhibitors such as GSK2879552. We also demonstrate that nLSD1p is enriched in PD-1CD8 T cells from resistant melanoma patients and 4T1 immunotherapy-resistant mice. Targeting the LSD1p nuclear axis induces IFN-γ/TNF-α-expressing CD8 T cell infiltration into the tumors of 4T1 immunotherapy-resistant mice, which is further augmented by combined immunotherapy. Underpinning these observations, nLSD1p is regulated by the key T cell exhaustion transcription factor EOMES in dysfunctional CD8 T cells. EOMES co-exists with nLSD1p in PD-1CD8 T cells in resistant patients, and nLSD1p regulates EOMES nuclear dynamics via demethylation/acetylation switching of critical EOMES residues. Using novel antibodies to target these post-translational modifications, we show that EOMES demethylation/acetylation is reciprocally expressed in resistant and responder patients. Overall, we show for the first time that dual inhibition of metastatic cancer cells and re-invigoration of the immune system requires LSD1 inhibitors that target the nLSD1p axis.
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http://dx.doi.org/10.3389/fimmu.2020.01228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7309504PMC
April 2021

What's on the Menu? Policies to Reduce Young People's Sugar Consumption.

Fisc Stud 2020 Mar 21;41(1):165-197. Epub 2020 May 21.

Institute for Fiscal Studies University College London.

Young people in the UK consume far above the maximum recommended levels of added sugar. It is likely that neither they nor their parents fully take account of the future health, social and economic costs of this high sugar consumption. This provides a rationale for policy intervention. The majority of young people's added sugar consumption occurs in the home, where purchases are typically made by parents. This means that understanding the purchase decisions of adults is important for policy design, even if the policies aim to reduce the consumption of young people. We discuss the merits of popular policies, including taxes, advertising restrictions and restrictions on the availability of specific foods, and we identify promising avenues for future research.
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http://dx.doi.org/10.1111/1475-5890.12194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7319480PMC
March 2020

Prevalence and sites of pain in remote-living older Aboriginal Australians, and associations with depressive symptoms and disability.

Intern Med J 2021 07;51(7):1092-1100

Western Australian Centre for Health and Ageing, University of Western Australia, Perth, Western Australia, Australia.

Background: Pain is a growing public health problem associated with significant health and functional implications. Limited data exist for Aboriginal Australians.

Aims: To describe the prevalence, severity and sites of pain, analgesic use and associated factors, including depression and disability, in remote-living Aboriginal Australians.

Methods: Cross-sectional study of 263 Aboriginal Australians aged ≥45 years from six remote Indigenous communities and the town of Derby in the Kimberley region of Western Australia between 2011 and 2013. Pain was assessed using a culturally adapted pain scale. Factors associated with pain were investigated with binary logistic regression.

Results: One hundred and seventy (64.6%) participants reported having pain and 53 (20.2%) reported persistent pain. Of those reporting pain, 61 (35.9%) rated it as moderate and 70 (41.2%) as severe. The most common sites of pain were back and knee, and 38 (22.4%) participants with pain indicated three or more sites of pain. Only 70 (41.2%) participants with pain were on some type of analgesic medication. After adjustment, poor vision (odds ratio (OR) = 2.21; 95% confidence interval (CI) 1.22-4.00), hypertension (OR = 1.89; 95% CI 1.03-3.45) and heart problems (OR = 2.05; 95% CI 1.01-4.14) were associated with pain. Higher depression scores were associated with more persistent pain, but pain was not significantly associated with clinically relevant depressive symptoms, or requiring assistance with two or more personal and/or instrumental activities of daily living.

Conclusion: High levels of pain were reported, although the prevalence of persistent pain was comparable to the general population. Identifying risk factors, improving pain recognition and assessment and evaluating culturally tailored management approaches should be a priority.
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http://dx.doi.org/10.1111/imj.14870DOI Listing
July 2021

Good Spirit, Good Life: A Quality of Life Tool and Framework for Older Aboriginal Peoples.

Gerontologist 2021 07;61(5):e163-e172

Centre for Aboriginal Medical and Dental Health, University of Western Australia, Perth.

Background And Objectives: The lack of appropriate quality of life (QoL) measures is a major barrier to planning and delivering health and aged care services for older Indigenous peoples worldwide. QoL is dependent on cultural values and priorities may vary between age groups. This project aims to develop a QoL tool for older Aboriginal Australians.

Research Design And Methods: The study was completed with Aboriginal Australians aged over 45 years living in Perth and Melbourne, Australia. Participatory Action Research methods were applied with an Indigenous research paradigm. Semistructured interviews were undertaken to identify the factors important to having a good life. Factors were further explored in yarning groups with older Aboriginal peoples to develop the draft QoL tool questions. Face validity of the tool was completed in two regions.

Results: The participants preferred the term "a good life" to QoL. Having a good spirit is at the core of having a good life. The protective factors for a good life were family and friends, health, culture, Elder role, respect, Country, spirituality, services and supports, community, future plans, safety and security, and basic needs.

Discussion And Implications: Twelve factors were identified and developed into key questions for the Good Spirit, Good Life tool. The draft tool will undergo quantitative validity testing, prior to embedding in service provision to inform care for older Aboriginal peoples. With local adaptation, the tool, accompanying framework, and participatory methods for development may have wider applicability to other Indigenous populations worldwide.
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http://dx.doi.org/10.1093/geront/gnz185DOI Listing
July 2021

Let's CHAT (community health approaches to) dementia in Aboriginal and Torres Strait Islander communities: protocol for a stepped wedge cluster randomised controlled trial.

BMC Health Serv Res 2020 Mar 12;20(1):208. Epub 2020 Mar 12.

The University of Melbourne, Faculty of Medicine, Dentistry and Health Sciences, Royal Melbourne Hospital, Royal Park Campus, Administration Building 21, 34 -54 Poplar Road, Melbourne, Victoria, 3052, Australia.

Background: Documented rates of dementia and cognitive impairment not dementia (CIND) in older Aboriginal and Torres Strait Islander Peoples is 3-5 times higher than the rest of the population, and current evidence suggests this condition is under-diagnosed and under-managed in a clinical primary care setting. This study aims to implement and evaluate a culturally responsive best practice model of care to optimise the detection and management of people with cognitive impairment and/or dementia, and to improve the quality of life of carers and older Aboriginal and Torres Islander Peoples with cognitive impairment.

Methods/design: The prospective study will use a stepped-wedge cluster randomised controlled trial design working with 12 Aboriginal Community Controlled Health Services (ACCHSs) across four states of Australia. Utilising a co-design approach, health system adaptations will be implemented including (i) development of a best practice guide for cognitive impairment and dementia in Aboriginal and Torres Strait Islander communities (ii) education programs for health professionals supported by local champions and (iii) development of decision support systems for local medical software. In addition, the study will utilise a knowledge translation framework, the Integrated Promoting Action on Research Implementation in Health Services (iPARIHS) Framework, to promote long-term sustainable practice change. Process evaluation will also be undertaken to measure the quality, fidelity and contextual influences on the outcomes of the implementation. The primary outcome measures will be rates of documentation of dementia and CIND, and evidence of improved management of dementia and CIND among older Indigenous peoples attending Aboriginal and Torres Strait Islander primary care services through health system changes. The secondary outcomes will be improvements to the quality of life of older Indigenous peoples with dementia and CIND, as well as that of their carers and families.

Discussion: The Let's CHAT Dementia project will co-design, implement and evaluate a culturally responsive best practice model of care embedded within current Indigenous primary health care. The best practice model of care has the potential to optimise the timely detection (especially in the early stages) and improve the ongoing management of people with dementia or cognitive impairment.

Trial Registration: ACTRN12618001485224. Date of registration: 04 of September 2019.
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http://dx.doi.org/10.1186/s12913-020-4985-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069169PMC
March 2020

Androgen Receptor and Poly(ADP-ribose) Glycohydrolase Inhibition Increases Efficiency of Androgen Ablation in Prostate Cancer Cells.

Sci Rep 2020 03 2;10(1):3836. Epub 2020 Mar 2.

Biomolecular Sciences Institute, Florida International University, Miami, FL, USA.

There is mounting evidence of androgen receptor signaling inducing genome instability and changing DNA repair capacity in prostate cancer cells. Expression of genes associated with base excision repair (BER) is increased with prostate cancer progression and correlates with poor prognosis. Poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) are key enzymes in BER that elongate and degrade PAR polymers on target proteins. While PARP inhibitors have been tested in clinical trials and are a promising therapy for prostate cancer patients with TMPRSS2-ERG fusions and mutations in DNA repair genes, PARG inhibitors have not been evaluated. We show that PARG is a direct androgen receptor (AR) target gene. AR is recruited to the PARG locus and induces PARG expression. Androgen ablation combined with PARG inhibition synergistically reduces BER capacity in independently derived LNCaP and LAPC4 prostate cancer cell lines. A combination of PARG inhibition with androgen ablation or with the DNA damaging drug, temozolomide, significantly reduces cellular proliferation and increases DNA damage. PARG inhibition alters AR transcriptional output without changing AR protein levels. Thus, AR and PARG are engaged in reciprocal regulation suggesting that the success of androgen ablation therapy can be enhanced by PARG inhibition in prostate cancer patients.
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http://dx.doi.org/10.1038/s41598-020-60849-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052214PMC
March 2020

The Well-Being of Carers of Older Aboriginal People Living in the Kimberley Region of Remote Western Australia: Empowerment, Depression, and Carer Burden.

J Appl Gerontol 2021 07 10;40(7):693-702. Epub 2020 Jan 10.

The University of Western Australia, Perth, Australia.

To describe demographic features and well-being of carers of Aboriginal Australians aged ≥45 years in remote Western Australia. Carer burden, empowerment, and depression were assessed in 124 Aboriginal carers in four remote Aboriginal communities. Carers were aged 38.8 ± 15.0 years, 73.4% were female, and 75.8% were children or grandchildren of the person cared for. The mean Zarit-6 score was 3.7 ± 3.6. Attending high school (odds ratio [OR] = 0.3; 95% confidence interval [CI] = [0.1, 0.7]) and feeling empowered (OR = 0.2; 95% CI = [0.1, 0.8]) were inversely associated with carer burden; female carers were less likely to feel empowered (OR = 0.4; 95% CI = [0.2, 0.9]); and empowerment was inversely associated with depression (OR = 0.3; 95% CI = [0.1, 0.7]). Aboriginal carers in remote communities are relatively young and most are children or grandchildren. Carer burden was lower than anticipated. However, existing tools may not adequately measure Aboriginal perspectives. Education and empowerment are key factors which support programs must consider.
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http://dx.doi.org/10.1177/0733464819898667DOI Listing
July 2021

Water quality induced corrosion of stainless steel valves during long-term service in a reverse osmosis system.

J Environ Sci (China) 2020 Mar 9;89:218-226. Epub 2019 Nov 9.

Beijing Yizhuang Water Co., Ltd., 100176, Beijing, China. Electronic address:

The current study analyzes the contribution of 10 water quality parameters (including pH, turbidity, conductivity, total dissolved solids (TDS), hardness, total organic carbon (TOC), alkalinity, calcium ions, chlorides and sulfates) to corrosion extent of stainless steel valves taken from different locations in a reverse osmosis system of a reclaimed water plant. The valves were in service for 5 years. Raman spectroscopy and X-ray photoelectron spectroscopy analyses are conducted to quantify corrosion products on different valves under various water quality conditions. On that basis, bivariate and multivariate regression analyses between the 10 water quality parameters and the corrosion extent of valve specimens (represented by metal loss percentage (MLP) values) are carried out to check the contribution of those water quality parameters to MLP. The results indicate that the proportions of metal oxides as corrosion products vary according to the corrosion extent of the valves. Although no linear correlation is found, all 10 water quality parameters except for pH show a significant positive correlation with the MLP values of the valve specimens. Moreover, results of multivariate regression suggest that the variation of MLP can be explained by turbidity, TDS, TOC and sulfates. A positive contribution of turbidity, TDS and TOC to MLP is observed, whereas the contribution of sulfates is negative. The results from the current work help to identify the reasons for water quality-induced failure of stainless steel equipment in RO systems.
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http://dx.doi.org/10.1016/j.jes.2019.10.008DOI Listing
March 2020

'Slope sign': a feature of large vessel vasculitis?

Ann Rheum Dis 2019 12 13;78(12):1738. Epub 2019 Sep 13.

Rheumatology, University of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, UK.

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http://dx.doi.org/10.1136/annrheumdis-2019-216213DOI Listing
December 2019

Assessing circovirus gene flow in multiple spill-over events.

Virus Genes 2019 Dec 28;55(6):802-814. Epub 2019 Aug 28.

School of Animal and Veterinary Sciences, Charles Sturt University, Boorooma Street, Wagga Wagga, NSW, 2650, Australia.

The establishment of viral pathogens in new host environments following spillover events probably requires adaptive changes within both the new host and pathogen. After many generations, signals for ancient cross-species transmission may become lost and a strictly host-adapted phylogeny may mimic true co-divergence while the virus may retain an inherent ability to jump host species. The mechanistic basis for such processes remains poorly understood. To study the dynamics of virus-host co-divergence and the arbitrary chances of spillover in various reservoir hosts with equal ecological opportunity, we examined structural constraints of capsid protein in extant populations of Beak and feather disease virus (BFDV) during known spillover events. By assessing reservoir-based genotype stratification, we identified co-divergence defying signatures in the evolution BFDV which highlighted primordial processes of cryptic host adaptation and competing forces of host co-divergence and cross-species transmission. We demonstrate that, despite extensive surface plasticity gathered over a longer span of evolution, structural constraints of the capsid protein allow opportunistic host switching in host-adapted populations. This study provides new insights into how small populations of endangered psittacine species may face multidirectional forces of infection from reservoirs with apparently co-diverging genotypes.
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http://dx.doi.org/10.1007/s11262-019-01702-xDOI Listing
December 2019

Structural characterization of a short-chain dehydrogenase/reductase from multi-drug resistant Acinetobacter baumannii.

Biochem Biophys Res Commun 2019 10 20;518(3):465-471. Epub 2019 Aug 20.

School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, 2678, Australia. Electronic address:

Acinetobacter baumannii (A. baumannii) is a clinically relevant, highly drug-resistant pathogen of global concern. An attractive approach to drug design is to specifically target the type II fatty acid synthesis (FASII) pathway which is critical in Gram negative bacteria and is significantly different to the type I fatty acid synthesis (FASI) pathway found in mammals. Enzymes involved in FASII include members of the short-chain dehydrogenase/reductase (SDR) superfamily. SDRs are capable of performing a diverse range of biochemical reactions against a broad spectrum of substrates whilst maintaining conserved structural features and sequence motifs. Here, we use X-ray crystallography to describe the structure of an SDR from the multi-drug resistant bacteria A. baumannii, previously annotated as a putative FASII FabG enzyme. The protein was recombinantly expressed, purified, and crystallized. The protein crystals diffracted to 2.0 Å and the structure revealed a FabG-like fold. Functional assays revealed, however, that the protein was not active against the FabG substrate, acetoacetyl-CoA. This study highlights that database annotations may show the necessary structural hallmarks of such proteins, however, they may not be able to cleave substrates that are typical of FabG enzymes. These results are important for the selection of target enzymes in future drug development.
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http://dx.doi.org/10.1016/j.bbrc.2019.08.056DOI Listing
October 2019

Integrating water quality and operation into prediction of water production in drinking water treatment plants by genetic algorithm enhanced artificial neural network.

Water Res 2019 Nov 23;164:114888. Epub 2019 Jul 23.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, China; Research Center for Environmental Nanotechnology (ReCENT), Nanjing University, Nanjing, 210023, China.

Stringent regulations and deteriorating source water quality could greatly influence the water production capacity of drinking water treatment plants (DWTPs). Using models to predict the performance of DWTPs under stress provides valuable information for decision making and future planning. A hybrid statistic model named HANN was established by combining artificial neural network (ANN) with genetic algorithm (GA) aiming at forecasting the overall performance of DWTPs nationwide in China. Monthly data from 45 DWTPs across China was employed. Water quality parameters like temperature and chemical oxygen demand (COD) and operational parameters like electricity consumption and chemical consumption were selected as input variables, while drinking water production was employed as the output. Both preliminary data analysis and principal component analysis (PCA) suggested a clear non-linear relationship between the input and output variables. The structure of the HANN model was optimized by employing the lowest mean squared error (MSE) as the indicator. The resultant HANN model performed well when simulating the training datasets. Its predictive accuracy for the independent test datasets was enhanced when feeding more training datasets and the performance was constantly higher than the independent multi-layered ANN models using the coefficient of determination (R) as the indicator, indicating the HANN model was capable of capturing complex non-linear relationship and extrapolation. Results from Accuracy test, Garson sensitivity analysis and Analysis of Variance (ANOVA) suggested the quantity of water produced by DWTPs was closely linked to water quality and operational parameters. The scenario analysis showed that the HANN model was capable of predicting water production variation based on the parameter variations, indicating that the HANN model could be a general management tool for decision makers and DWTP managers to make plans in advance of regulatory changes, source water quality variations and market demand.
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http://dx.doi.org/10.1016/j.watres.2019.114888DOI Listing
November 2019
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