Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are chronic inflammatory diseases that together affect 2-3% of the population. RA and AS predominantly involve joints, but heart disease is also a common feature in RA and AS patients. Here we have studied a new spontaneous mutation that causes severe polyarthritis in bone phenotype spontaneous mutation 1 (BPSM1) mice. In addition to joi...

The instinct of thirst was a cardinal element in the successful colonization by vertebrates of the dry land of the planet, which began in the Ordovician period about 400 million y ago. It is a commonplace experience in humans that drinking water in response to thirst following fluid loss is a pleasant experience. However, continuing to drink water once thirst has been satiated becomes unpleasan...

MicroRNAs (miRNAs) regulate a wide variety of biological processes and contribute to metabolic homeostasis. Here, we demonstrate that microRNA-223 (miR-223), an miRNA previously associated with inflammation, also controls multiple mechanisms associated with cholesterol metabolism. miR-223 promoter activity and mature levels were found to be linked to cellular cholesterol states in hepatoma cell...

Rupture of a vulnerable atherosclerotic plaque causes thrombus formation and precipitates cardiovascular diseases. In addition to the thrombogenic content of a plaque, also the hemodynamic microenvironment plays a major role in thrombus formation. How the altered hemodynamics around a plaque promote pathological thrombus formation is not well understood. In this study, we provide evidence that ...

MicroRNAs are dysregulated in a setting of heart disease and have emerged as promising therapeutic targets. MicroRNA-34 family members (miR-34a, -34b, and -34c) are up-regulated in the heart in response to stress. In this study, we assessed whether inhibition of the miR-34 family using an s.c.-delivered seed-targeting 8-mer locked nucleic acid (LNA)-modified antimiR (LNA-antimiR-34) can provide...

Background: Aboriginal and Torres Strait Islanders (Aboriginal) are Australia's first peoples. Between 2006 and 2015, HIV notifications increased among Aboriginal people; however, among non-Aboriginal people, notifications remained relatively stable. This systematic review and meta-analysis aims to examine the prevalence of HIV among Aboriginal people overall and by subgroups. Methods: In Novem...

BACKGROUND: Diagnoses of chlamydia and gonorrhoea have increased steadily in Australia over the past decade. Testing and treatment is central to prevention and control but in some settings treatment may be delayed. Testing at the point of care has the potential to reduce these delays. We explored the potential utility of newly available accurate point-of-care tests in various clinical settin...

Background Point-of-care (POC) tests could be important public health tools in settings with treatment delays and high rates of sexually transmissible infections (STIs). Use is limited due to suboptimal performance. The performance and ease-of-use of a new molecular-based POC test for simultaneous detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) was assessed, alongside two...

Background Despite the availability of testing and treatment, bacterial sexually transmissible infections (STIs) continue to occur at endemic levels in many remote Indigenous communities in Australia. New generation molecular point-of-care (POC) tests have high sensitivity, comparable with conventional diagnostic tests, and have the potential to increase the impact of STI screening. Methods: We...

Background Rapid point-of-care tests (POCTs) for chlamydia (Chlamydia trachomatis) and gonorrhoea (Neisseria gonorrhoeae) have the potential to confer health benefits in certain populations even at moderate sensitivities; however, suitable POCTs for these organisms are currently lacking. Methods: In this study, we investigated the use of direct urine polymerase chain reaction (PCR), with the vi...

We aimed to document how health service providers in the Torres Strait Island region of northern Australia respond to chronic hepatitis B, and to identify priorities for the effective clinical management of the infection. Semi-structured qualitative interviews with 61 health service providers were conducted in 2011 in the Torres Strait and north Queensland region to explore issues affecting chr...

Global concerns about rising levels of chronic disease make timely translation of research into policy and practice a priority. There is a need to tackle common risk factors: tobacco use, unhealthy diets, physical inactivity, and harmful alcohol use. Using evidence to inform policy and practice is challenging, often hampered by a poor fit between academic research and the needs of policymakers ...

BACKGROUND: Although the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain. METHODS: We analyzed data from 68.5 million persons to assess the trends in the prevalence of overweight and obesity among children and adults between 1980 and 2015. Using the Global Burden of Disea...

BACKGROUND: Among patients with chronic heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority...

BACKGROUND: In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial fo...

The pathways through which fatty acids induce insulin resistance have been the subject of much research. We hypothesise that by focussing on the reversal of insulin resistance, novel insights can be made regarding the mechanisms by which insulin resistance can be overcome. Using global gene and lipid expression profiling, we aimed to identify biological pathways altered during the prevention of...

BACKGROUND: How cardiovascular (CV) events affect progression to end-stage renal disease (ESRD), particularly in the setting of type 2 diabetes, remains uncertain. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 4,022 patients with type 2 diabetes, anemia, and chronic kidney disease from the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). PREDICTOR: ...

BACKGROUND: Although assessment of cardiovascular safety is mandated by regulatory agencies for the development of new drugs to treat type 2 diabetes, evaluation of their renal safety has been relatively neglected. STUDY DESIGN: Individual patient-level data pooled analysis of 13 phase 2 or 3 randomized, double-blind, placebo-controlled, clinical trials of the dipeptidyl peptidase 4 inhibito...

BACKGROUND: Low serum 25-hydroxyvitamin D (25[OH]D) levels have been associated with chronic kidney disease in cross-sectional studies. However, this association has not been studied prospectively in a large general population-based cohort. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 6,180 adults 25 years or older participating in the baseline and 5-year follow-up...

BACKGROUND: Sparse data are available about the natural history of hemoglobin (Hb) level trends in contemporary patients with anemia, chronic kidney disease (CKD), and type 2 diabetes mellitus. We intended to describe Hb level trends over time with no or minimal administration of erythropoiesis-stimulating agents. STUDY DESIGN: Prospective clinical trial cohort. SETTING & PARTICIPANTS: 2,019 ...