The effects of exercise and adipose tissue lipolysis on plasma adiponectin concentration and adiponectin receptor expression in human skeletal muscle

Objective It has been suggested that adiponectin regulates plasma free fatty acid (FFA) clearance by stimulating FFA uptake and/or oxidation in muscle. We aimed to determine changes in plasma adiponectin concentration and adiponectin receptor 1 and 2 mRNA expression in skeletal muscle during and after prolonged exercise under normal, fasting conditions (high FFA trial; HFA) and following pharmacological inhibition of adipose tissue lipolysis (low FFA trial; LFA). Furthermore, we aimed to detect and locate adiponectin in skeletal muscle tissue. Methods Ten subjects performed two exercise trials (120 min at 50% VO2max). Indirect calorimetry was used to determine total fat oxidation rate. Plasma samples were collected at rest, during exercise and during post-exercise recovery to determine adiponectin, FFA and glycerol concentrations. Muscle biopsies were taken to determine adiponectin protein and adiponectin receptor 1 and 2 mRNA expression and to localise intramyocellular adiponectin. Results Basal plasma adiponectin concentrations averaged 6.57±0.7 and 6.63±0.8 mg/l in the HFA and LFA trials respectively, and did not change significantly during or after exercise. In the LFA trial, plasma FFA concentrations and total fat oxidation rates were substantially reduced. However, plasma adiponectin and muscle adiponectin receptor 1 and 2 mRNA expression did not differ between trials. Immunohistochemical staining of muscle cross-sections showed the presence of adiponectin in the sarcolemma of individual muscle fibres and within the interfibrillar arterioles. Conclusion Plasma adiponectin concentrations and adiponectin receptor 1 and 2 mRNA expression in muscle are not acutely regulated by changes in adipose tissue lipolysis and/or plasma FFA concentrations. Adiponectin is abundantly expressed in muscle, and, for the first time, it has been shown to be present in/on the sarcolemma of individual muscle fibres.

Expression and regulation of vascular endothelial growth factor ligands and receptors during menstruation and post-menstrual repair of human endometrium

Regeneration and growth of the human endometrium after shedding of the functional layer during menstruation depends on an adequate angiogenic response. We analysed the mRNA expression levels of all known vascular endothelial growth factor (VEGF) ligands and receptors in human endometrium collected in the menstrual and proliferative phases of the menstrual cycle. In addition, we evaluated the expression of VEGF-A, VEGF-R2 and NRP-1 at the protein level. Two periods of elevated mRNA expression of ligands and receptors were observed, separated by a distinct drop at cycle days (CDs) 9 and 10. Immunohistochemical staining showed that VEGF and VEGF-R2 were expressed in epithelial, stromal and endothelial cells. NRP-1 was mainly confined to stroma and blood vessels; only in late-proliferative endometrium, epithelial staining was also observed. Except for endothelial VEGF-R2 expression in CDs 6-8, there were no significant differences in the expression of VEGF, VEGF-R2 or NRP-1 in any of the cell compartments. In contrast, VEGF release by cultured human endometrium explants decreased during the proliferative phase. This output was significantly reduced in menstrual and early-proliferative endometrium by estradiol (E2) treatment. Western blot analysis indicated that part of the VEGF-A was trapped in the extracellular matrix (ECM). Changes in VEGF ligands and receptors were associated with elevated expression of the hypoxia markers HIF1 alpha and CA-IX in the menstrual and early proliferative phases. HIF1 alpha was also detected in late-proliferative phase endometrium. Our findings indicate that VEGF-A exerts its actions mostly during the first half of the proliferative phase. Furthermore, VEGF-A production appears to be triggered by hypoxia in the menstrual phase and subsequently suppressed toy estrogen during the late proliferative phase.

Protein-energy malnutrition exists and is associated with negative outcomes in morbidly obese hospital patients

Prevalence of protein-energy malnutrition (PEM), food intake inadequacy and associated health-related outcomes in morbidly obese (Body Mass Index ≥ 40 kg/m2) acute care patients are unknown. This study reports findings in morbidly obese participants from the Australasian Nutrition Care Day Survey (ANCDS) conducted in 2010. The ANCDS was a cross-sectional survey involving acute care patients from 56 Australian and New Zealand hospitals. Hospital-based dietitians evaluated participants’ nutritional status (defined by Subjective Global Assessment, SGA) and 24-hour food intake (as 0%, 25%, 50%, 75%, and 100% of the offered food). Three months later, outcome data, including length of stay (LOS) and 90-day in-hospital mortality, were collected. Of the 3122 participants, 4% (n = 136) were morbidly obese (67% females, 55 ± 14 years, BMI: 48 ± 8 kg/m2). Eleven percent (n = 15) of the morbidly obese patients were malnourished, and most (n = 11/15, 73%)received standard hospital diets without additional nutritional support. Malnourished morbidly obese patients had significantly longer LOS and greater 90-day in-hospital mortality than well-nourished counterparts (23 days vs. 9 days, p = 0.036; 14% vs. 0% mortality, p = 0.011 respectively). Thirteen morbidly obese patients (10%) consumed only 25% of the offered meals with a significantly greater proportion of malnourished (n = 4, 27%) versus well-nourished (n = 9, 7%) (p = 0.018). These results provide new knowledge on the prevalence of PEM and poor food intake in morbidly obese patients in Australian and New Zealand hospitals. For the first time internationally, the study establishes that PEM is significantly associated with negative outcomes in morbidly obese patients and warrants timely nutritional support during hospitalisation.

Estrogen and the endometrium: lessons learned from gene expression profiling in rodents and human

To date, research into the biological processes and molecular mechanisms associated with endometrial receptivity and embryo implantation has been a focus of attention, whereas the complex events that occur in the human endometrium during the menstrual and proliferative phase under the influence of estrogen have received little attention. The objective of this review is to provide an update of our current understanding of the actions of estrogen on both human and rodent endometrium, with special emphasis on the regulation of uterine growth and cell proliferation, and the value of global gene expression analysis, in increasing understanding of these processes.

Haemoglobin expression in human endometrium

BACKGROUND: The general concept that haemoglobin is only a carrier protein for oxygen and carbon dioxide is challenged since recent studies have shown haemoglobin expression in non-erythroid cells and the protection of haemoglobin against oxidative and nitrosative stress. Using microarrays, we previously showed expression of haemoglobins alpha, beta, delta and gamma and the haeme metabolizing enzyme, haeme oxygenase (HO)-1 in human endometrium. METHODS: Using real-time quantitative PCR, haemoglobin alpha, beta, delta and gamma, and HO-1 mRNA levels were assessed throughout the menstrual cycle (n = 30 women). Haemoglobin and HO-1 protein levels in the human endometrium were assessed with immunohistochemistry. For steroid responsiveness, menstrual and late proliferative-phase endometrial explants were cultured for 24 h in the presence of vehicle (0.1% ethanol), estradiol (17 beta-E-2, 1 nM), progestin (Org 2058, 1 nM) or 17 beta-E-2+Org 2058 (1 nM each). RESULTS: All haemoglobins and the HO-1 were expressed in normal human endometrium. Haemoglobin mRNA and protein expression did not vary significantly during the menstrual cycle. Explant culture with Org 2058 or 17 beta-E-2+Org 2058 increased haemoglobin gamma mRNA expression (P < 0.05). HO-1 mRNA levels, and not protein levels, were significantly higher during the menstrual (M)-phase of the cycle (P < 0.05), and were down-regulated by Org 2058 in M-phase explants and by 17 beta-E-2+Org 2058 in LP-phase explants, versus control (P < 0.05). CONCLUSIONS: The haemoglobin-HO-1 system may be required to ensure adequate regulation of the bioavailability of haeme, iron and oxygen in human endometrium.

Reproducibility of subjective appetite ratings and ad libitum test meal energy intake in overweight and obese males

Background To determine whether changes in appetite and energy intake (EI) can be detected and play a role in the effectiveness of interventions, it is necessary to identify their variability under normal conditions. We assessed the reproducibility of subjective appetite ratings and ad libitum test meal EI after a standardised pre-load in overweight and obese males. Methods Fifteen overweight and obese males (BMI 30.3 ± 4.9 kg/m2, aged 34.9 ± 10.6 years) completed two identical test days, 7 days apart. Participants were provided with a standardised fixed breakfast (1676 kJ) and 5 h later an ad libitum pasta lunch. An electronic appetite rating system was used to assess subjective ratings before and after the fixed breakfast, and periodically during the postprandial period. EI was assessed at the ad libitum lunch meal. Sample size estimates for paired design studies were calculated. Results Appetite ratings demonstrated a consistent oscillating pattern between test days, and were more reproducible for mean postprandial than fasting ratings. The correlation between ad libitum EI on the two test days was r = 0.78 (P < 0.01). Using a paired design and a power of 0.8, a minimum of 12 participants would be needed to detect a 10 mm change in 5 h postprandial mean ratings and 17 to detect a 500 kJ difference in ad libitum EI. Conclusion Intra-individual variability of appetite and ad libitum test meal EI in overweight and obese males is comparable to previous reports in normal weight adults. Sample size requirements for studies vary depending on the parameter of interest and sensitivity needed.

Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease

Chronic kidney disease (CKD) in ageing is a burden on health systems worldwide. Rat models of age-related CKD linked with obesity and hypertension were used to investigate alterations in oxidant handling and energy metabolism to identify gene targets or markers for age-related CKD. Young adult (3 months) and old (21–24 months) spontaneously-hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Wistar rats (normotensive, obese in ageing) were compared for renal functional and physiological parameters, renal fibrosis and inflammation, oxidative stress (hemeoxygenase-1/HO-1), apoptosis and cell injury (including Bax:Bcl-2), phosphorylated and non-phosphorylated forms of oxidant and energy sensing proteins (p66Shc, AMPK), signal transduction proteins (ERK1/2, PKB), and transcription factors (NF-κB, FoxO1). All old rats were normoglycemic. Renal fibrosis, tubular epithelial apoptosis, interstitial macrophages and myofibroblasts (all p < 0.05), p66Shc/phospho-p66 (p < 0.05), Bax/Bcl-2 ratio (p < 0.05) and NF-κB expression (p < 0.01) were highest in old obese Wistars. Expression of phospho-FoxO/FoxO was elevated in old Wistars (p < 0.001) and WKYs (p < 0.01). SHRs had high levels in young and old rats. Expression of PKB, phospho-PKB, ERK1/2 and phospho-ERK1/2 were significantly elevated in all aged animals. These results suggest that obesity and hypertension have differing oxidant handling and signalling pathways that act in the pathogenesis of age-related CKD

The impact of a congestion pricing exemption on the demand for new energy efficient vehicles in Stockholm

As governments seek to transition to more efficient vehicle fleets, one strategy has been to incentivize ‘green’ vehicle choice by exempting some of these vehicles from road user charges. As an example, to stimulate sales of Energy-Efficient Vehicles (EEVs) in Sweden, some of these automobiles were exempted from Stockholm’s congestion tax. In this paper the effect this policy had on the demand for new, privately-owned, exempt EEVs is assessed by first estimating a model of vehicle choice and then by applying this model to simulate vehicle alternative market shares under different policy scenarios. The database used to calibrate the model includes owner-specific demographics merged with vehicle registry data for all new private vehicles registered in Stockholm County during 2008. Characteristics of individuals with a higher propensity to purchase an exempt EEV were identified. The most significant factors included intra-cordon residency (positive), distance from home to the CBD (negative), and commuting across the cordon (positive). By calculating vehicle shares from the vehicle choice model and then comparing these estimates to a simulated scenario where the congestion tax exemption was inactive, the exemption was estimated to have substantially increased the share of newly purchased, private, exempt EEVs in Stockholm by 1.8% (+/- 0.3%; 95% C.I.) to a total share of 18.8%. This amounts to an estimated 10.7% increase in private, exempt EEV purchases during 2008 i.e. 519 privately owned, exempt EEVs.

Relationship between EGFR expression, EGFR mutation status, and the efficacy of chemotherapy plus cetuximab in FLEX study patients with advanced non-small-cell lung cancer

INTRODUCTION: The phase III FLEX study (NCT00148798) in advanced non-small-cell lung cancer indicated that the survival benefit associated with the addition of cetuximab to cisplatin and vinorelbine was limited to patients whose tumors expressed high levels of epidermal growth factor receptor (EGFR) (immunohistochemistry score of >/=200; scale 0-300). We assessed whether the treatment effect was also modulated in FLEX study patients by tumor EGFR mutation status. METHODS: A tumor mutation screen of EGFR exons 18 to 21 included 971 of 1125 (86%) FLEX study patients. Treatment outcome in low and high EGFR expression groups was analyzed across efficacy endpoints according to tumor EGFR mutation status. RESULTS: Mutations in EGFR exons 18 to 21 were detected in 133 of 971 tumors (14%), 970 of which were also evaluable for EGFR expression level. The most common mutations were exon 19 deletions and L858R (124 of 133 patients; 93%). In the high EGFR expression group (immunohistochemistry score of >/=200), a survival benefit for the addition of cetuximab to chemotherapy was demonstrated in patients with EGFR wild-type (including T790M mutant) tumors. Although patient numbers were small, those in the high EGFR expression group whose tumors carried EGFR mutations may also have derived a survival benefit from the addition of cetuximab to chemotherapy. Response data suggested a cetuximab benefit in the high EGFR expression group regardless of EGFR mutation status. CONCLUSIONS: The survival benefit associated with the addition of cetuximab to first-line chemotherapy for advanced non-small-cell lung cancer expressing high levels of EGFR is not limited by EGFR mutation status.

Renewing the Sustainable Energy Curriculum – Providing Internationally Relevant Skills for a Carbon Constrained Economy : Final Report 2014

The aims of the project were to scope and develop sustainable energy curriculum frameworks for Australian higher education Institutions that meet the needs of Australian and international student graduates and employers, both now and into the near future. The focus was on student centred learning and outcomes and to support graduates with the knowledge, skills and generic attributes required to work in the rapidly expanding sustainable energy industry in Australia and globally. The outputs of the project are designed to be relevant to specialist Sustainable Engineering and Energy Studies programs, as well as conventional engineering, science and humanities and social science programs that have a sustainable energy focus or major.

Renewing the Sustainable Energy Curriculum : Curriculum Frameworks and Guidance for Course Delivery

This guide is to support institutions in developing and teaching tertiary level programmes for sustainable energy professionals. Ongoing curriculum renewal is more difficult but vital for multidisciplinary courses preparing graduates to work in a specialised rapidly changing field. After more than 15 years of offering tertiary level “sustainable energy” qualifications in Australian Universities there was a clear need to assess how these courses are taught and develop curriculum frameworks to guide Universities designing/redesigning programs and courses to provide graduates with the relevant skills, knowledge and attributes (capabilities) seen by graduates and employers as required to work in this rapidly changing field. This guide presents the sustainable energy curriculum frameworks developed by the “Renewing the sustainable energy curriculum – providing internationally relevant skills for a carbon constrained economy” project, which was conducted over a two-and-a-quarter year period.

The impact of Cool Roof applications on energy performance : results from Australian sub-tropical and tropical field studies

Cool roof coatings are identified by their solar reflectance index. They have been reported to have multiple benefits, the extent of which are strongly dependent on the peculiarities of the local climate, building stock and electricity network. This paper presents measured and simulated data from residential, educational and commercial buildings involved in recent field trials in Australia. The purpose of the field trials was to evaluate the impact of such coatings on electricity demand and load and to assess their potential application to improve comfort whilst avoiding the need for air conditioners. Measured reductions in temperature, power (kW) and energy (kWh) were used to develop a predictive model that correlates ambient temperature distribution profiles, building demand reduction profiles and electricity network peak demand times. Combined with simulated data, the study indicates the types of buildings that could be targeted in Demand Management programs for the mutual benefit of electricity networks and building occupants.

Developing affordable and sustainable housing through energy, transport, and building utility integration

Housing affordability and sustainable development are not polarised ideologies as both are necessary with increasing urbanisation. We must bridge the gap between current median house pricing and target affordable house pricing whilst pursuing sustainability. This paper examines the potential of initial construction cost and ongoing utilities and transport cost reduction through the integration of sustainable housing design and transit oriented development principles in a Commuter Energy and Building Utilities System (CEBUS). It also introduces current research on the development of a Dynamic Simulation Model for CEBUS applications in the Australian property development and construction industry.

Aggregating energy supply and demand

Energy usage in general, and electricity usage in particular, are major concerns internationally due to the increased cost of providing energy supplies and the environmental impacts of electricity generation using carbon-based fuels. If a "systems" approach is taken to understanding energy issues then both supply and demand need to be considered holistically. This paper examines two research projects in the energy area with IT tools as key deliverables, one examining supply issues and the other studying demand side issues. The supply side project used hard engineering methods to build the models and software, while the demand side project used a social science approach. While the projects are distinct, there was an overlap in personnel. Comparing the knowledge extraction, model building, implementation and interface issues of these two deliverables identifies both interesting contrasts and commonalities.

Integrating PV systems into distribution networks with battery energy storage systems

Integrating Photovoltaic (PV) systems with battery energy storage in the distribution network will be essential to allow for continued uptake of domestic PV system installations. With increasing concerns regarding environmental and climate change issues, incorporating sources of renewable energy into power networks across the world will be key for a sustainable future. Australia is well placed to utilise solar energy as a significant component of its future energy generation and within the last 5 years there has been a rapid growth in the penetration levels seen by the grid. This growth of PV systems is causing a number of issues including intermittency of supply, negative power flow and voltage rises. Using the simulator tool GridLAB-D with a model of a typical South-East Queensland (SEQ) 11 kV distribution feeder, the effect of various configurations of PV systems have been offset with Battery Energy Storage Systems (BESS). From this, combinations of PV and storage that are most effective at mitigating the issues were explored.