Mineralocorticoid receptors modulate vascular endothelial function in human obesity

Abstract Obesity increases linearly with age and is associated with impaired vascular endothelial function and increased risk of cardiovascular disease. MRs (mineralocorticoid receptors) contribute to impaired vascular endothelial function in cardiovascular disease; however, their role in uncomplicated human obesity is unknown. Because plasma aldosterone levels are elevated in obesity and adipocytes may be a source of aldosterone, we hypothesized that MRs modulate vascular endothelial function in older adults in an adiposity-dependent manner. To test this hypothesis, we administered MR blockade (eplerenone; 100 mg/day) for 1 month in a balanced randomized double-blind placebo-controlled cross-over study to 22 older adults (ten men, 55--79 years) varying widely in adiposity [BMI (body mass index): 20--45 kg/m 2 ], but who were free from overt cardiovascular disease. We evaluated vascular endothelial function [brachial artery FMD (flow-mediated dilation)] via ultrasonography) and oxidative stress (plasma F 2 -isoprostanes and vascular endothelial cell protein expression of nitrotyrosine and NADPH oxidase p47 phox ) during placebo and MR blockade. In the whole group, oxidative stress (P > 0.05) and FMD did not change with MR blockade (6.39 + − 0.67 compared with 6.23 + − 0.73 %; P = 0.7). However, individual improvements in FMD in response to eplerenone were associated with higher total body fat (BMI: r = 0.45, P = 0.02; and dual-energy X-ray absorptiometry-derived percentage body fat: r = 0.50, P = 0.009) and abdominal fat (total: r = 0.61, P = 0.005; visceral: r = 0.67, P = 0.002; and subcutaneous: r = 0.48, P = 0.03). In addition, greater improvements in FMD with eplerenone were related to higher baseline fasting glucose (r = 0.53, P = 0.01). MRs influence vascular endothelial function in an adiposity-dependent manner in healthy older adults

Defining Natural History: Assessment of the Ability of College Students to Aid in Characterizing Clinical Progression of Niemann-Pick Disease, Type C

Niemann-Pick Disease, type C (NPC) is a fatal, neurodegenerative, lysosomal storage disorder. It is a rare disease with broad phenotypic spectrum and variable age of onset. These issues make it difficult to develop a universally accepted clinical outcome measure to assess urgently needed therapies. To this end, clinical investigators have defined emerging, disease severity scales. The average time from initial symptom to diagnosis is approximately 4 years. Further, some patients may not travel to specialized clinical centers even after diagnosis. We were therefore interested in investigating whether appropriately trained, community-based assessment of patient records could assist in defining disease progression using clinical severity scores. In this study we evolved a secure, step wise process to show that pre-existing medical records may be correctly assessed by non-clinical practitioners trained to quantify disease progression. Sixty-four undergraduate students at the University of Notre Dame were expertly trained in clinical disease assessment and recognition of major and minor symptoms of NPC. Seven clinical records, randomly selected from a total of thirty seven used to establish a leading clinical severity scale, were correctly assessed to show expected characteristics of linear disease progression. Student assessment of two new records donated by NPC families to our study also revealed linear progression of disease, but both showed accelerated disease progression, relative to the current severity scale, especially at the later stages. Together, these data suggest that college students may be trained in assessment of patient records, and thus provide insight into the natural history of a disease

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined (T1D+T2D) GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 diabetic subjects (and 18,582 DKD cases). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, p=4.5×10-8) associated with 'microalbuminuria' in European T2D cases. However, no replication of this signal was observed in Asian subjects with T2D, or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously-reported DKD signals, except for those at UMOD and PRKAG2, both associated with 'EGFR'. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk-variant discovery for DKD.</p

The impact of financial toxicity on quality of life for survivors of primary brain tumour

Purpose Despite the well-known impacts of financial hardship on cancer survivors, financial toxicity experienced in the context of brain tumour has received little attention. This study examined factors related to financial toxicity, and associations between financial toxicity, anxiety and quality of life (QoL) in this population. Method Adults with primary brain tumour were recruited from hospital and community services as part of a telehealth psychological intervention study. They completed a telephone cognitive screener at pre-intervention, and the Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT), Generalised Anxiety Disorder-7 (GAD-7) and Functional Assessment of Cancer Therapy-Brain (FACT-Br) as part of a 6-week post-intervention assessment. Results Sixty brain tumour survivors (60% female; M age = 47.90, SD = 14.47) participated. Most of the sample (57%) experienced mild to moderate financial toxicity. Individuals with high-grade glioma reported significantly higher levels of financial toxicity compared to those with benign brain tumour. Greater perceived symptoms, lower global cognitive status and higher anxiety symptoms were significantly associated with higher financial toxicity. Financial toxicity contributed significant unique variance in QoL (4.2%), controlling for covariates. Anxiety symptoms partially mediated the relationship between financial toxicity and QoL (β = 0.24, CI 0.03, 0.55). Conclusions Higher levels of financial toxicity are related to tumour type (high-grade glioma), lower cognitive status, greater perceived symptoms and anxiety. Brain tumour survivors with higher financial toxicity are more likely to experience lower QoL, which may in part be related to greater anxiety symptoms. Implications for cancer survivors Financial burden is associated with higher anxiety and lower quality of life for brain tumour survivors. These findings highlight the importance of early screening and access to personalised financial advice and support.Full Tex

A randomised controlled trial of \u27clockwise\u27 ultrasound for low back pain.

Aims: To examine how the choice of words explaining ultrasound (US) may influence the outcome of physiotherapy treatment for low back pain (LBP). Methods: Sixty-seven patients with LBP \u3c 3 months were randomly allocated to one of three groups - traditional education about US (control group [CG]), inflated education about US (experimental group [EG]) or extra-inflated education about US (extra-experimental group [EEG]). Each patient received the exact same application of US that has shown clinical efficacy for LBP (1.5 Watts/cm Results: Both EG and EEG groups showed a statistically significant improvement for SLR ( Conclusion: The choice of words when applying a treatment in physiotherapy can alter the efficacy of the treatment

A randomised controlled trial of ‘clockwise’ ultrasound for low back pain

Aims: To examine how the choice of words explaining ultrasound (US) may influence the outcome of physiotherapy treatment for low back pain (LBP). Methods: Sixty-seven patients with LBP < 3 months were randomly allocated to one of three groups – traditional education about US (control group [CG]), inflated education about US (experimental group [EG]) or extra-inflated education about US (extra-experimental group [EEG]). Each patient received the exact same application of US that has shown clinical efficacy for LBP (1.5 Watts/cm2 for 10 minutes at 1 Megahertz, pulsed 20% over a 20 cm2 area), but received different explanations (CG, EG or EEG). Before and immediately after US,measurements of LBP and leg pain (numeric rating scale), lumbar flexion (distance to floor) and straight leg raise (SLR) (inclinometer) were taken. Statistical analysis consisted of mixed-factorial analyses of variance and chi-square analyses to measure differences between the three groups, as well as meeting or exceeding minimal detectable changes (MDCs) for pain, lumbar flexion and SLR. Results: Both EG and EEG groups showed a statistically significant improvement for SLR (p < 0.0001), while the CG did not. The EEG group participants were 4.4 times (95% confidence interval: 1.1 to 17.5) more likely to improve beyond the MDC than the CG. No significant differences were found between the groups for LBP, leg pain or lumbar flexion. Conclusion: The choice of words when applying a treatment in physiotherapy can alter the efficacy of the treatment

Effect of Selective Mineralocorticoid Receptor Blockade on Flow-Mediated Dilation and Insulin Resistance in Older Adults with Metabolic Syndrome

Background: The prevalence of metabolic syndrome is especially high in older adults. Metabolic syndrome is associated with impaired vascular endothelial function, insulin resistance, and increased risk for cardiovascular disease but the underlying mechanisms are not fully elucidated. Plasma aldosterone is independently associated with metabolic syndrome and is linked to endothelial dysfunction and insulin resistance. Thus, we hypothesized that mineralocorticoid receptor (MR) blockade would improve flow-mediated dilation and insulin resistance in older adults with metabolic syndrome. Methods: To test this hypothesis, we conducted a balanced, randomized, double-blind, placebo-controlled, crossover study using selective MR blockade (eplerenone; 100 mg/day) for 1 month with 1 month washout in older adults with metabolic syndrome (62.6 ± 3.2 yrs; mean ± standard error). We evaluated brachial artery flow-mediated dilation (ultrasonography), oxidative stress (oxidized low-density lipoproteins and F(2)-isoprostanes) and insulin resistance (homeostatic model assessment). Results: In response to MR blockade, flow-mediated dilation (5.37 ± 0.85 vs. 5.98 ± 1.29%; placebo vs. eplerenone; P = 0.4), oxidized low-density lipoproteins (51.6 ± 11.5 vs. 56.1 ± 10.9 U/L; P = 0.6), and F(2)-isoprostanes (0.07 ± 0.02 vs. 0.06 ± 0.01 pg/mL; P = 0.3) did not improve. Insulin resistance also did not change following MR blockade (1.04 ± 0.26 vs. 1.38 ± 0.50; P = 0.6). However, MR blockade resulted in a large reduction (10 mmHg) in systolic blood pressure (140 ± 6 vs. 130 ± 6 mmHg; P = 0.02), with no significant change in diastolic blood pressure (81 ± 3 vs. 75 ± 2 mmHg; P = 0.2). Conclusions: Our data do not support a contributing role for MRs in endothelial dysfunction and insulin resistance in older adults with metabolic syndrome. However, our findings suggest MR activation is an important contributor to systolic hypertension in this patient group

Eleven: Best Of 100 Songs Project 2012

Eleven original recordings curated by leading industry figures. This is a compilation album from QUT's 2012 100 Songs project. It's called Eleven: Best of 100 Songs Project 2012 and was released in May 2013. It’s an 11 track album with a bonus track, full of remixed, rerecorded and rejigged tracks from the project that were shortlisted by our friends at MGM Distribution, Mushroom Music, Island Records and Music Sales Australia. The Eleven album is already receiving critical acclaim from Australia's music industry

The Mathematics Value Inventory for General Education Students: Development and Initial Validation

The goal of this study was to develop a self-report inventory that measures individual differences in the perceived value of mathematical literacy for general education students.The Mathematics Value Inventory (MVI) is grounded in the Eccles et al. model of achievement-related choices and surveys students’ beliefs in four areas: interest, general utility, need for high achievement, and personal cost. This study describes the development and initial score validation of the MVI. As hypothesized, it was found that (a) MVI scores for students who were not majoring in math did not differ by gender, (b) students who had higher MVI scores had completed more college course work in math than did students with lower scores, and (c) MVI scores were not related to scores on a measure of social desirability.</jats:p