Postprandial total and HMW adiponectin following a high-fat meal in lean, obese and diabetic men

BACKGROUND/OBJECTIVES: Recent work suggests that macronutrients are pro-inflammatory and promote oxidative stress. Reports of postprandial regulation of total adiponectin have been mixed, and there is limited information regarding postprandial changes in high molecular weight (HMW) adiponectin. The aim of this study was to assess the effect of a standardised high-fat meal on metabolic variables, adiponectin (total and HMW), and markers of inflammation and oxidative stress in: (i) lean, (ii) obese non-diabetic and (iii) men with type 2 diabetes mellitus (T2DM). SUBJECTS/METHODS: Male subjects: lean (n=10), obese (n=10) and T2DM (n=10) were studied for 6 h following both a high-fat meal and water control. Metabolic variables (glucose, insulin, triglycerides), inflammatory markers (interleukin-6 (IL6), tumour necrosis factor (TNF)α, high-sensitivity C-reactive protein (hsCRP), nuclear factor (NF)κB expression in peripheral blood mononuclear cells (p65)), indicators of oxidative stress (oxidised low density lipoprotein (oxLDL), protein carbonyl) and adiponectin (total and HMW) were measured. RESULTS: No significant changes in TNFα, p65, oxLDL or protein carbonyl concentrations were observed. Overall, postprandial IL6 decreased in subjects with T2DM but increased in lean subjects, whereas hsCRP decreased in the lean cohort and increased in obese subjects. There was no overall postprandial change in total or HMW adiponectin in any group. Total adiponectin concentrations changed over time following the water control, and the response was significantly different in lean subjects compared with subjects with T2DM (P=0.04). CONCLUSIONS: No consistent significant postprandial inflammation, oxidative stress or regulation of adiponectin was observed in this study. Findings from the water control suggest differential basal regulation of total adiponectin in T2DM compared with lean controls.

Increasing electrospun scaffold pore size with tailored collectors for improved cell penetration

This study investigates the use of patterned collectors to increase the pore size of electrospun scaffolds for enhanced cell infiltration. The morphology of the patterned scaffolds was investigated by scanning electron microscopy, which showed that the collector pattern was accurately mimicked by the electrospun fibres. We observed an enlargement in the pore size and in the pore size distribution compared with conventional electrospinning. Mechanical testing revealed that the mechanical properties could be tailored, to some extent, according to the patterning and that the patterned scaffolds were softer than standard electrospun scaffolds. When NIH 3T3 fibroblasts were seeded onto patterned collectors improved cell infiltration was observed. Cells were able to penetrate up to 250 μm into the scaffolds, compared with 30 μm for the standard scaffolds. This increase in the depth of infiltration occurred as early as 24 h post-seeding and remained constant over 7 days.

Encouraging, assisting, and time to eat : comparison of mealtime assistance interventions in elderly medical inpatients

BACKGROUND: The prevalence of protein-energy malnutrition in older adults is reported to be as high as 60% and is associated with poor health outcomes. Inadequate feeding assistance and mealtime interruptions may contribute to malnutrition and poor nutritional intake during hospitalisation. Despite being widely implemented in practice in the United Kingdom and increasingly in Australia, there have been few studies examining the impact of strategies such as Protected Mealtimes and dedicated feeding assistant roles on nutritional outcomes of elderly inpatients. AIMS: The aim of this research was to implement and compare three system-level interventions designed to specifically address mealtime barriers and improve energy intakes of medical inpatients aged ≥65 years. This research also aimed to evaluate the sustainability of any changes to mealtime routines six months post-intervention and to gain an understanding of staff perceptions of the post-intervention mealtime experience. METHODS: Three mealtime assistance interventions were implemented in three medical wards at Royal Brisbane and Women's Hospital: AIN-only: Additional assistant-in-nursing (AIN) with dedicated nutrition role. PM-only: Multidisciplinary approach to meals, including Protected Mealtimes. PM+AIN: Combined intervention: AIN + multidisciplinary approach to meals. An action research approach was used to carefully design and implement the three interventions in partnership with ward staff and managers. Significant time was spent in consultation with staff throughout the implementation period to facilitate ownership of the interventions and increase likelihood of successful implementation. A pre-post design was used to compare the implementation and nutritional outcomes of each intervention to a pre-intervention group. Using the same wards, eligible participants (medical inpatients aged ≥65 years) were recruited to the preintervention group between November 2007 and March 2008 and to the intervention groups between January and June 2009. The primary nutritional outcome was daily energy and protein intake, which was determined by visually estimating plate waste at each meal and mid-meal on Day 4 of admission. Energy and protein intakes were compared between the pre and post intervention groups. Data were collected on a range of covariates (demographics, nutritional status and known risk factors for poor food intake), which allowed for multivariate analysis of the impact of the interventions on nutritional intake. The provision of mealtime assistance to participants and activities of ward staff (including mealtime interruptions) were observed in the pre-intervention and intervention groups, with staff observations repeated six months post-intervention. Focus groups were conducted with nursing and allied health staff in June 2009 to explore their attitudes and behaviours in response to the three mealtime interventions. These focus group discussions were analysed using thematic analysis. RESULTS: A total of 254 participants were recruited to the study (pre-intervention: n=115, AIN-only: n=58, PM-only: n=39, PM+AIN: n=42). Participants had a mean age of 80 years (SD 8), and 40% (n=101) were malnourished on hospital admission, 50% (n=108) had anorexia and 38% (n=97) required some assistance at mealtimes. Occasions of mealtime assistance significantly increased in all interventions (p<0.01). However, no change was seen in mealtime interruptions. No significant difference was seen in mean total energy and protein intake between the preintervention and intervention groups. However, when total kilojoule intake was compared with estimated requirements at the individual level, participants in the intervention groups were more likely to achieve adequate energy intake (OR=3.4, p=0.01), with no difference noted between interventions (p=0.29). Despite small improvements in nutritional adequacy, the majority of participants in the intervention groups (76%, n=103) had inadequate energy intakes to meet their estimated energy requirements. Patients with cognitive impairment or feeding dependency appeared to gain substantial benefit from mealtime assistance interventions. The increase in occasions of mealtime assistance by nursing staff during the intervention period was maintained six-months post-intervention. Staff focus groups highlighted the importance of clearly designating and defining mealtime responsibilities in order to provide adequate mealtime care. While the purpose of the dedicated feeding assistant was to increase levels of mealtime assistance, staff indicated that responsibility for mealtime duties may have merely shifted from nursing staff to the assistant. Implementing the multidisciplinary interventions empowered nursing staff to "protect" the mealtime from external interruptions, but further work is required to empower nurses to prioritise mealtime activities within their own work schedules. Staff reported an increase in the profile of nutritional care on all wards, with additional non-nutritional benefits noted including improved mobility and functional independence, and better identification of swallowing difficulties. IMPLICATIONS: The PhD research provides clinicians with practical strategies to immediately introduce change to deliver better mealtime care in the hospital setting, and, as such, has initiated local and state-wide roll-out of mealtime assistance programs. Improved nutritional intakes of elderly inpatients was observed; however given the modest effect size and reducing lengths of hospital stays, better nutritional outcomes may be achieved by targeting the hospital-to-home transition period. Findings from this study suggest that mealtime assistance interventions for elderly inpatients with cognitive impairment and/or functional dependency show promise.

Effects of size of health service on scope of rural nursing practice

This paper presents the findings of an analysis of the activities of rural nurses from a national audit of the role and function of the rural nurse (Hegney, Pearson and McCarthy 1997). The results suggest that the size of the health service (defined by the number of acute beds) influences the activities of rural nurses. Further, the study reports on the differences of the context of practice between different size rural health services and the impact this has on the scope of rural nursing practice. The paper will conclude that the size of the health service is an outcome of rurality (small population densities, distance from larger health facilities, lack of on-site medical and allied health staff). It also notes that the size of the health service is a major contextual determinant of patient acuity and staff skill-mix in small rural hospitals, and therefore the scope of rural nursing practice.

Dry powder inhaler formulations-effect of polymer carrier size on the drug dispersion

Background The size of the carrier influences the aerosolization of drug from a dry powder inhaler (DPI) formulation. Currently, lactose monohydrate particles in a variety of sizes are preferably used in carrier based DPI formulations of various drugs; however, contradictory reports exist regarding the effect of the size of the carrier on the dispersion of drug. In this study we examined the influence of the intrinsic particle size of the polymeric carrier on the aerosolization of a model drug salbutamol sulphate (SS). Methods Four different sizes (20–150 lm) of polymer carriers were fabricated using solvent evaporation technique and the dispersion of SS particles from these carriers was measured by a Twin Stage Impinger (TSI). The size and morphological properties of polymer carriers were by laser diffraction and SEM, respectively. Results The FPF from these carriers was found to be increasing from 5.6% to 21.3% with increasing the carrier size. The FPF was found to be greater (21%) with the highest particle size of the carrier (150 lm). Conclusions The aerosolization of drug was dependent on the size of polymer carriers. The smaller size of the carrier resulted in lower FPF which was increased with increasing the carrier size. For a fixed mass of drug particles in a formulation, the mass of drug particles per unit area of carriers is higher in formulations containing the larger carriers, which leads to an increase in the dispersion of drug due to the increased mechanical forces occurred between the carriers and the device walls.

The impact of neighborhood walkability on walking : does it differ across adult life stage and does neighborhood buffer size matter?

We explored the impact of neighborhood walkability on young adults, early-middle adults, middle-aged adults, and older adults' walking across different neighborhood buffers. Participants completed the Western Australian Health and Wellbeing Surveillance System Survey (2003–2009) and were allocated a neighborhood walkability score at 200 m, 400 m, 800 m, and 1600 m around their home. We found little difference in strength of associations across neighborhood size buffers for all life stages. We conclude that neighborhood walkability supports more walking regardless of adult life stage and is relevant for small (e.g., 200 m) and larger (e.g., 1600 m) neighborhood buffers.

A practical and theoretical definition of very small field size for radiotherapy output factor measurements

Purpose This work introduces the concept of very small field size. Output factor (OPF) measurements at these field sizes require extremely careful experimental methodology including the measurement of dosimetric field size at the same time as each OPF measurement. Two quantifiable scientific definitions of the threshold of very small field size are presented. Methods A practical definition was established by quantifying the effect that a 1 mm error in field size or detector position had on OPFs, and setting acceptable uncertainties on OPF at 1%. Alternatively, for a theoretical definition of very small field size, the OPFs were separated into additional factors to investigate the specific effects of lateral electronic disequilibrium, photon scatter in the phantom and source occlusion. The dominant effect was established and formed the basis of a theoretical definition of very small fields. Each factor was obtained using Monte Carlo simulations of a Varian iX linear accelerator for various square field sizes of side length from 4 mm to 100 mm, using a nominal photon energy of 6 MV. Results According to the practical definition established in this project, field sizes < 15 mm were considered to be very small for 6 MV beams for maximal field size uncertainties of 1 mm. If the acceptable uncertainty in the OPF was increased from 1.0 % to 2.0 %, or field size uncertainties are 0.5 mm, field sizes < 12 mm were considered to be very small. Lateral electronic disequilibrium in the phantom was the dominant cause of change in OPF at very small field sizes. Thus the theoretical definition of very small field size coincided to the field size at which lateral electronic disequilibrium clearly caused a greater change in OPF than any other effects. This was found to occur at field sizes < 12 mm. Source occlusion also caused a large change in OPF for field sizes < 8 mm. Based on the results of this study, field sizes < 12 mm were considered to be theoretically very small for 6 MV beams. Conclusions Extremely careful experimental methodology including the measurement of dosimetric field size at the same time as output factor measurement for each field size setting and also very precise detector alignment is required at field sizes at least < 12 mm and more conservatively < 15 mm for 6 MV beams. These recommendations should be applied in addition to all the usual considerations for small field dosimetry, including careful detector selection.

A comparison of surface doses for very small field size x-ray beams : Monte Carlo calculations and radiochromic film measurements

Stereotactic radiosurgery treatments involve the delivery of very high doses for a small number of fractions. To date, there is limited data in terms of the skin dose for the very small field sizes used in these treatments. In this work, we determine relative surface doses for small size circular collimators as used in stereotactic radiosurgery treatments. Monte Carlo calculations were performed using the BEAMnrc code with a model of the Novalis 15 Trilogy linear accelerator and the BrainLab circular collimators. The surface doses were calculated at the ICRU skin dose depth of 70 m all using the 6 MV SRS x-ray beam. The calculated surface doses varied between 15 – 12% with decreasing values as the field size increased from 4 to 30 mm. In comparison, surface doses were measured using Gafchromic EBT3 film positioned at the surface of a Virtual Water phantom. The absolute agreement between calculated and measured surface doses was better than 2.5% which is well within the 20 uncertainties of the Monte Carlo calculations and the film measurements. Based on these results, we have shown that the Gafchromic EBT3 film is suitable for surface dose estimates in very small size fields as used in SRS.

Using narrow beam profiles to quantify focal spot size, for accurate Monte Carlo simulations of SRS/SRT systems

This study investigates the variation of photon field penumbra shape with initial electron beam diameter, for very narrow beams. A Varian Millenium MLC (Varian Medical Systems, Palo Alto, USA) and a Brainlab m3 microMLC (Brainlab AB. Feldkirchen, Germany) were used, with one Varian iX linear accelerator, to produce fields that were (nominally) 0.20 cm across. Dose profiles for these fields were measured using radiochromic film and compared with the results of simulations completed using BEAMnrc and DOSXYZnrc, where the initial electron beam was set to FWHM = 0.02, 0.10, 0.12, 0.15, 0.20 and 0.50 cm. Increasing the electron-beam FWHM produced increasing occlusion of the photon source by the closely spaced collimator leaves and resulted in blurring of the simulated profile widths from 0.26 to 0.64 cm, for the MLC, from 0.12 to 0.43 cm, for the microMLC. Comparison with measurement data suggested that the electron spot size in the clinical linear accelerator was between FWHM = 0.10 and 0.15 cm, encompassing the result of our previous output-factor based work, which identified a FWHM of 0.12. Investigation of narrow-beam penumbra variation has been found to be a useful procedure, with results varying noticeably with linear accelerator spot size and allowing FWHM estimates obtained using other methods to be verified.

Characteristics of spatial variation, size distribution, formation and growth of particles in urban environments

This thesis is the first comprehensive study of important parameters relating to aerosols' impact on climate and human health, namely spatial variation, particle size distribution and new particle formation. We determined the importance of spatial variation of particle number concentration in microscale environments, developed a method for particle size parameterisation and provided knowledge about the chemistry of new particle formation. This is a significant contribution to our understanding of processes behind the transformation and dynamics of urban aerosols. This PhD project included extensive measurements of air quality parameters using state of the art instrumentation at each of the 25 sites within the Brisbane metropolitan area and advanced statistical analysis.

Pore size distribution and accessible pore size distribution in bituminous coals

The porosity and pore size distribution of coals determine many of their properties, from gas release to their behavior on carbonization, and yet most methods of determining pore size distribution can only examine a restricted size range. Even then, only accessible pores can be investigated with these methods. Small-angle neutron scattering (SANS) and ultra small-angle neutron scattering (USANS) are increasingly used to characterize the size distribution of all of the pores non-destructively. Here we have used USANS/SANS to examine 24 well-characterized bituminous and subbituminous coals: three from the eastern US, two from Poland, one from New Zealand and the rest from the Sydney and Bowen Basins in Eastern Australia, and determined the relationships of the scattering intensity corresponding to different pore sizes with other coal properties. The range of pore radii examinable with these techniques is 2.5nm to 7μm. We confirm that there is a wide range of pore sizes in coal. The pore size distribution was found to be strongly affected by both rank and type (expressed as either hydrogen or vitrinite content) in the size range 250nm to 7μm and 5 to 10nm, but weakly in intermediate regions. The results suggest that different mechanisms control coal porosity on different scales. Contrast-matching USANS and SANS were also used to determine the size distribution of the fraction of the pores in these coals that are inaccessible to deuterated methane, CD4, at ambient temperature. In some coals most of the small (~10nm) pores were found to be inaccessible to CD4 on the time scale of the measurement (~30min–16h). This inaccessibility suggests that in these coals a considerable fraction of inherent methane may be trapped for extended periods of time, thus reducing the effectiveness of methane release from (or sorption by) these coals. Although the number of small pores was less in higher rank coals, the fraction of total pores that was inaccessible was not rank dependent. In the Australian coals, at the 10nm to 50nm size scales the pores in inertinites appeared to be completely accessible to CD4, whereas the pores in the vitrinite were about 75% inaccessible. Unlike the results for total porosity that showed no regional effects on relationships between porosity and coal properties, clear regional differences in the relationships between fraction of closed porosity and coal properties were found. The 10 to 50nm-sized pores of inertinites of the US and Polish coals examined appeared less accessible to methane than those of the inertinites of Australian coals. This difference in pore accessibility in inertinites may explain why empirical relationships between fluidity and coking properties developed using Carboniferous coals do not apply to Australian coals.

Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction : a model for cross-modulation

Background A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. Methods PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. Results When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk. Conclusion ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.

An endogenously deposited fibrin scaffold determines construct size in the surgically created arteriovenous loop chamber model of tissue engineering

Background: An arteriovenous loop (AVL) enclosed in a polycarbonate chamber in vivo, produces a fibrin exudate which acts as a provisional matrix for the development of a tissue engineered microcirculatory network. Objectives: By administering enoxaparin sodium - an inhibitor of fibrin polymerization, the significance of fibrin scaffold formation on AVL construct size (including the AVL, fibrin scaffold, and new tissue growth into the fibrin), growth, and vascularization were assessed and compared to controls. Methods: In Sprague Dawley rats, an AVL was created on femoral vessels and inserted into a polycarbonate chamber in the groin in 3 control groups (Series I) and 3 experimental groups (Series II). Two hours before surgery and 6 hours post-surgery, saline (Series I) or enoxaparin sodium (0.6 mg/kg, Series II) was administered intra-peritoneally. Thereafter, the rats were injected daily with saline (Series I) or enoxaparin sodium (1.5 mg/kg, Series II) until construct retrieval at 3, 10, or 21 days. The retrieved constructs underwent weight and volume measurements, and morphologic/morphometric analysis of new tissue components. Results: Enoxaparin sodium treatment resulted in the development of smaller AVL constructs at 3, 10, and 21 days. Construct weight and volume were significantly reduced at 10 days (control weight 0.337 ± 0.016 g [Mean ± SEM] vs treated 0.228 ± 0.048, [P < .001]: control volume 0.317 ± 0.015 mL vs treated 0.184 ± 0.039 mL [P < .01]) and 21 days (control weight 0.306 ± 0.053 g vs treated 0.198 ± 0.043 g [P < .01]: control volume 0.285 ± 0.047 mL vs treated 0.148 ± 0.041 mL, [P < .01]). Angiogenesis was delayed in the enoxaparin sodium-treated constructs with the absolute vascular volume significantly decreased at 10 days (control vascular volume 0.029 ± 0.03 mL vs treated 0.012 ± 0.002 mL [P < .05]). Conclusion: In this in vivo tissue engineering model, endogenous, extra-vascularly deposited fibrin volume determines construct size and vascular growth in the first 3 weeks and is, therefore, critical to full construct development.