Hydrous mantle transition zone indicated by ringwoodite included within diamond.

The ultimate origin of water in the Earth's hydrosphere is in the deep Earth--the mantle. Theory and experiments have shown that although the water storage capacity of olivine-dominated shallow mantle is limited, the Earth's transition zone, at depths between 410 and 660 kilometres, could be a major repository for water, owing to the ability of the higher-pressure polymorphs of olivine--wadsleyite and ringwoodite--to host enough water to comprise up to around 2.5 per cent of their weight.

Circulating natriuretic peptide concentrations reflect changes in insulin sensitivity over time in the Diabetes Prevention Program.

Aims/hypothesis: We aimed to study the relationship between measures of adiposity, insulin sensitivity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the Diabetes Prevention Program (DPP).

Methods: The DPP is a completed clinical trial. Using stored samples from this resource, we measured BMI, waist circumference (WC), an insulin sensitivity index (ISI; [1/HOMA-IR]) and NT-proBNP at baseline and at 2 years of follow-up in participants randomised to placebo (n = 692), intensive lifestyle intervention (n = 832) or metformin (n = 887).

The contribution of twins to the study of cognitive ageing and dementia: the Older Australian Twins Study.

The Older Australian Twins Study (OATS) is a major longitudinal study of twins, aged ≥ 65 years, to investigate genetic and environmental factors and their interactions in healthy brain ageing and neurocognitive disorders. The study collects psychiatric, neuropsychological, cardiovascular, metabolic, biochemical, neuroimaging, genomic and proteomic data, with two-yearly assessments, and is currently in its third wave. The initial cohort comprises 623 individuals (161 monozygotic and 124 dizygotic twin pairs; 1 MZ triplets; 27 single twins and 23 non-twin siblings), of whom 426 have had wave 2 assessment.

Sydney Memory and Ageing Study: an epidemiological cohort study of brain ageing and dementia.

Non-demented community-dwelling older adults aged 70-90 years (n = 1,037) randomly recruited from the electoral roll completed neuropsychological and medical assessments over six years. The overall prevalence of mild cognitive impairment (MCI) at baseline was 36.7%.

Clinical use of adiponectin as a marker of metabolic dysregulation.

Adiponectin concentrations exhibit strong cross-sectional relationships with obesity, inflammation, and diabetes. Adiponectin concentrations have been extensively evaluated as epidemiologic markers of diabetes and cardiovascular disease risk. In the present review we will provide an overview of these epidemiologic relationships as the backdrop for an evaluation of the clinical applications of adiponectin measurements.

The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data.

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects.

DNA methylation of the MAPT gene in Parkinson's disease cohorts and modulation by vitamin E in vitro.

Parkinson's disease (PD) is a neurodegenerative disorder for which environmental factors influence disease risk and may act via an epigenetic mechanism. The microtubule-associated protein tau (MAPT) is a susceptibility gene for idiopathic PD. Methylation levels were determined by pyrosequencing of bisulfite-treated DNA in a leukocyte cohort (358 PD patients and 1084 controls) and in two brain cohorts (Brain1, comprising 69 cerebellum controls; and Brain2, comprising 3 brain regions from 28 PD patients and 12 controls).

Metabolic syndrome components and their response to lifestyle and metformin interventions are associated with differences in diabetes risk in persons with impaired glucose tolerance.

Aims: To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence.

Methods: We used the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III) revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years.

[13C]glucose breath testing provides a noninvasive measure of insulin resistance: calibration analyses against clamp studies.

Background: Exhaled (13)CO2 following ingestion of [(13)C]glucose with a standard oral glucose tolerance load correlates with blood glucose values but is determined by tissue glucose uptake. Therefore exhaled (13)CO2 may also be a surrogate measure of the whole-body glucose disposal rate (GDR) measured by the gold standard hyperinsulinemic euglycemic clamp.

Subjects And Methods: Subjects from across the glycemia range were studied on 2 consecutive days under fasting conditions.

Lifestyle and metformin treatment favorably influence lipoprotein subfraction distribution in the Diabetes Prevention Program.

Context: Although intensive lifestyle change (ILS) and metformin reduce diabetes incidence in subjects with impaired glucose tolerance (IGT), their effects on lipoprotein subfractions have not been studied.

Objective: The objective of the study was to characterize the effects of ILS and metformin vs placebo interventions on lipoprotein subfractions in the Diabetes Prevention Program.

Design: This was a randomized clinical trial, testing the effects of ILS, metformin, and placebo on diabetes development in subjects with IGT.

GSK3B and MAPT polymorphisms are associated with grey matter and intracranial volume in healthy individuals.

The microtubule-associated protein tau gene (MAPT) codes for a protein that plays an integral role in stabilisation of microtubules and axonal transport in neurons. As well as its role in susceptibility to neurodegeneration, previous studies have found an association between the MAPT haplotype and intracranial volume and regional grey matter volumes in healthy adults. The glycogen synthase kinase-3β gene (GSK3B) codes for a serine/threonine kinase that phosphorylates various proteins, including tau, and has also been associated with risk for neurodegenerative disorders and schizophrenia.

Does hormone therapy affect blood pressure changes in the Diabetes Prevention Program?

Objective: This study aims to examine whether blood pressure reductions differ by estrogen use among overweight glucose-intolerant women.

Methods: We conducted a secondary analysis of Diabetes Prevention Program postmenopausal participants who used oral estrogen with or without progestogen at baseline and 1-year follow-up (n = 324) versus those who did not use oral estrogen with or without progestogen at either time point (n = 382). Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were examined by randomization arm (intensive lifestyle change [ILS], metformin 850 mg twice daily, or placebo).

Effect of acarbose to delay progression of carotid intima-media thickness in early diabetes.

Background: The anti-diabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes.

Methods: The Early Diabetes Intervention Program was a randomized trial of acarbose versus placebo in 219 participants with early diabetes characterized by glucose values over 11.

APOE genotype and MRI markers of cerebrovascular disease: systematic review and meta-analysis.

Objective: We aimed to examine the association of APOE ε genotype with MRI markers of cerebrovascular disease (CVD): white matter hyperintensities, brain infarcts, and cerebral microbleeds.

Methods: We performed a systematic review and meta-analysis of 42 cross-sectional or longitudinal studies identified in PubMed from 1966 to June 2012 (n = 29,965). This included unpublished data from 3 population-based studies: 3C-Dijon, Framingham Heart Study, and Sydney Memory and Ageing Study.

Detection of islet β-cell death in vivo by multiplex PCR analysis of differentially methylated DNA.

Noninvasive detection of early β-cell death in type 1 diabetes might identify individuals in whom therapeutic interventions would preserve β-cell mass and prevent hyperglycemia. Recent studies in mice have shown that β-cell death produces a corresponding increase in unmethylated preproinsulin (PPI) DNA in serum. Here, we report the development of a novel assay using dual fluorescent-probe multiplex PCR (TaqMan) to detect differential methylation of circulating PPI DNA.

Sex steroid levels and response to weight loss interventions among postmenopausal women in the diabetes prevention program.

Objectives: To examine whether estrogen use potentiates weight loss interventions via sex steroid levels and whether endogenous sex steroid levels predict response to weight loss interventions among women not using estrogen.

Methods: The Diabetes Prevention Program randomized overweight or obese dysglycemic participants to lifestyle change with the goals of weight reduction of >7% of initial weight and 150 minutes per week of exercise, metformin, or placebo. In this secondary analysis, we examined sex steroid levels and reductions in weight and waist circumference (WC) among postmenopausal women using (n = 324) and not using (n = 382) oral estrogen.

Risk factors for late-life cognitive decline and variation with age and sex in the Sydney Memory and Ageing Study.

Introduction: An aging population brings increasing burdens and costs to individuals and society arising from late-life cognitive decline, the causes of which are unclear. We aimed to identify factors predicting late-life cognitive decline.

Methods: Participants were 889 community-dwelling 70-90-year-olds from the Sydney Memory and Ageing Study with comprehensive neuropsychological assessments at baseline and a 2-year follow-up and initially without dementia.

Impaired cardiometabolic responses to glucagon-like peptide 1 in obesity and type 2 diabetes mellitus.

Glucagon-like peptide 1 (GLP-1) has insulin-like effects on myocardial glucose uptake which may contribute to its beneficial effects in the setting of myocardial ischemia. Whether these effects are different in the setting of obesity or type 2 diabetes (T2DM) requires investigation. We examined the cardiometabolic actions of GLP-1 (7-36) in lean and obese/T2DM humans, and in lean and obese Ossabaw swine.

Pentoxifylline, inflammation, and endothelial function in HIV-infected persons: a randomized, placebo-controlled trial.

Background: Untreated HIV may increase the risk of cardiovascular events. Our preliminary in vitro and in vivo research suggests that pentoxifylline (PTX) reduces vascular inflammation and improves endothelial function in HIV-infected persons not requiring antiretroviral therapy.

Methods: We performed a randomized, placebo-controlled trial of PTX 400 mg orally thrice daily for 8 weeks in 26 participants.

Factors predicting reversion from mild cognitive impairment to normal cognitive functioning: a population-based study.

Introduction: Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. However, many individuals diagnosed with MCI are found to have reverted to normal cognition on follow-up. This study investigated factors predicting or associated with reversion from MCI to normal cognition.

Vitamin C prevents the acute decline of flow-mediated dilation after altered shear rate patterns.

Oscillatory and retrograde shear rate (SR) impairs endothelial function, potentially through shear-induced oxidative stress. We tested the hypothesis that acute vitamin C supplementation would prevent the attenuation of brachial artery flow-mediated dilation (FMD) after a period of augmented oscillatory and retrograde SR. Twelve healthy men (aged 26 ± 3 years) participated in two 30-min study visits in which one arm was subjected to increased oscillatory and retrograde SR, using 60 mm Hg of forearm cuff compression, and the contralateral arm served as the control.

An essential RNA element resides in a central region of hepatitis E virus ORF2.

Hepatitis E virus (genus Hepevirus, family Hepeviridae) is one of the most important causes of acute hepatitis in adults, particularly among pregnant women, throughout Asia and Africa where mortality rates can be 20-30 %. Hepatitis E virus has a single-stranded positive-sense RNA genome that contains three translated ORFs. The two 3' ORFs are translated from a subgenomic RNA.

The Sydney Centenarian Study: methodology and profile of centenarians and near-centenarians.

Background: The study of exceptionally long-living individuals can inform us about the determinants of successful aging. There are few population-based studies of centenarians and near-centenarians internationally, but none in Australia.

Methods: Individuals 95 years and older were recruited from seven electoral districts in Sydney using the electoral roll, Medicare lists, and multiple other strategies to obtain a representative sample.

Insulin resistance in the vasculature.

Insulin resistance is typically defined as a reduced ability of insulin to induce glucose uptake by target tissues such as fat and skeletal muscle cells. It accompanies several disease states, including obesity, type 2 diabetes, hepatitis C, and polycystic ovary syndrome, and is a primary feature of metabolic syndrome. Outside of its effects on blood glucose levels, insulin resistance is also associated with a 2- to 3-fold increased risk of cardiovascular mortality.

The vascular endothelium in diabetes--a therapeutic target?

Insulin resistance affects the vascular endothelium, and contributes to systemic insulin resistance by directly impairing the actions of insulin to redistribute blood flow as part of its normal actions driving muscle glucose uptake. Impaired vascular function is a component of the insulin resistance syndrome, and is a feature of type 2 diabetes. On this basis, the vascular endothelium has emerged as a therapeutic target where the intent is to improve systemic metabolic state by improving vascular function.