Differential effects of exercise on insulin-signaling gene expression in human skeletal muscle.

Skeletal muscle insulin sensitivity is enhanced after acute exercise and short-term endurance training. We investigated the impact of exercise on the gene expression of key insulin-signaling proteins in humans. Seven untrained subjects (4 women and 3 men) completed 9 days of cycling at 63 ± 2% of peak O₂ uptake for 60 min/day. Muscle biopsies were taken before, immediately after, and 3 h after the exercise bouts (on days 1 and 9). The gene expression of insulin receptor substrate-2 and the p85α subunit of phosphatidylinositol 3-kinase was significantly higher 3 h after a single exercise bout, although short-term training ameliorated this effect. Gene expression of insulin receptor and insulin receptor substrate-1 was not significantly altered at any time point. These results suggest that exercise may have a transitory impact on the expression of insulin receptor substrate-2 and phosphatidylinositol 3-kinase; however, the predominant actions of exercise on insulin sensitivity appear not to reside in the transcriptional activation of the genes encoding major insulin-signaling proteins.

Exercise training increases lipid metabolism gene expression in human skeletal muscle

The effects of a single bout of exercise and exercise training on the expression of genes necessary for the transport and beta -oxidation of fatty acids (FA), together with the gene expression of transcription factors implicated in the regulation of FA homeostasis were investigated. Seven human subjects (3 male, 4 female, 28.9 ± 3.1 yr of age, range 20-42 yr, body mass index 22.6 kg/m², range 17-26 kg/m²) underwent a 9-day exercise training program of 60 min cycling per day at 63% peak oxygen uptake (V_{O2 peak}; 104 ± 14 W). On days 1 and 9 of the program, muscle biopsies were sampled from the vastus lateralis muscle at rest, at the completion of exercise, and again 3 h postexercise. Gene expression of key components of FA transport [FA translocase (FAT/CD36), plasma membrane-associated FA-binding protein], beta -oxidation [carntine palmitoyltransferase(CPT) I, beta -hydroxyacyl-CoA dehydrogenase] and transcriptional control [peroxisome proliferator-activated receptor (PPAR)alpha , PPARgamma , PPARgamma coactivator 1, sterol regulatory element-binding protein-1c] were unaltered by exercise when measured at the completion and at 3 h postexercise. Training increased total lipid oxidation by 24% (P < 0.05) for the 1-h cycling bout. This increased capacity for lipid oxidation was accompanied by an increased expression of FAT/CD36 and CPT I mRNA. Similarly, FAT/CD36 protein abundance was also upregulated by exercise training. We conclude that enhanced fat oxidation after exercise training is most closely associated with the genes involved in regulating FA uptake across the plasma membrane (FAT/CD36) and across the mitochondrial membrane (CPT I).

Response : A defensible and workable approach to the income tax treatment of financial instruments

It is a privilege to have the opportunity to respond to the comments on my monograph1 provided by Mark Gergen, Glenn May, and Gordon Longhouse. Their comments, which are inevitably coloured by their very different perspectives, reflect the considerable expertise that each one of them has in the area of the income taxation of financial instruments. Indeed, it is with some hesitation that I offer a response in defence of various portions of the analysis presented in my monograph in support of some pretty modest proposals in this extremely difficult area of income tax law. Although I spent considerable time exploring some necessary first principles and their implications for the design of a system for the income taxation of financial instruments, I made several concessions to certain practical constraints that led me to support, in some measure, the status quo reflected in certain of the existing literature, as well as the legislation in a select group of countries. On the assumption that many readers may be unfamiliar with the monograph, I propose to respond by outlining much of my analysis in the monograph and the proposals that are the logical outcome. Throughout the outline, I will highlight and respond to what I see as the important points of difference emphasized by Gergen, May, and Longhouse.

The effect of insulin and exercise on c-Cbl protein abundance and phosphorylation in insulin-resistant skeletal muscle in lean and obese Zucker rats.

Aims/hypothesis: Recruitment of the protein c-Cbl to the insulin receptor (IR) and its tyrosine phosphorylation via a pathway that is independent from phosphatidylinositol 3prime-kinase is necessary for insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. The activation of this pathway by insulin or exercise has yet to be reported in skeletal muscle. Methods: Lean and obese Zucker rats were randomly assigned to one of three treatment groups: (i) control, (ii) insulin-stimulated or (iii) acute, exhaustive exercise. Hind limb skeletal muscle was removed and the phosphorylation state of IR, Akt and c-Cbl measured.  Results:   Insulin receptor phosphorylation was increased 12-fold after insulin stimulation (p<0.0001) in lean rats and threefold in obese rats. Acute exercise had no effect on IR tyrosine phosphorylation. Similar results were found for serine phosphorylation of Akt. Exercise did not alter c-Cbl tyrosine phosphorylation in skeletal muscle of lean or obese rats. However, in contrast to previous studies in adipocytes, c-Cbl tyrosine phosphorylation was reduced after insulin treatment (p<0.001). Conclusions/interpretation: We also found that c-Cbl associating protein expression is relatively low in skeletal muscle of Zucker rats compared to 3T3-L1 adipocytes and this could account for the reduced c-Cbl tyrosine phosphorylation after insulin treatment. Interestingly, basal levels of c-Cbl tyrosine phosphorylation were higher in skeletal muscle from insulin-resistant Zucker rats (p<0.05), but the physiological relevance is not clear. We conclude that the regulation of c-Cbl phosphorylation in skeletal muscle differs from that previously reported in adipocytes.

A trial of nurse practitioner scope of practice

Aims. The aim of this paper is to report a trial to investigate the feasibility of the nurse practitioner role in local health service delivery and to provide information about the educational and legislative requirements for nurse practitioner practice.

Background. Nurse practitioners have been shown to offer a beneficial service and fill a gap in health care provision. However, the lack of publications describing, critiquing, or defending the way that existing nurse practitioner roles have been developed may lead to a lack of clarity in comparing the nurse practitioner scope of practice internationally. In Australia, credible exploratory research is needed to realize the potential of nurse practitioners to bridge the divide of inequitable distribution of health services. A trial of nurse practitioner services in the Australian Capital Territory provided an excellent opportunity to investigate these scope and continuity issues.

Methods. This was an observational analytic study using multiple data sources. Four models of nurse practitioner service were chosen from a competitive field of applications that were evaluated according to efficacy, feasibility, and sustainability across specified selection criteria. Each model in the trial included a clinical support team, with the nurse practitioner candidate 'working-into-the-role' and collecting demographic, clinical practice, patient outcome, and health service and consumer survey data over a 10 month period.

Findings. The trial identified the broad potential of the nurse practitioner role, its breadth and limitations, and its impact on selected health services in the Australian Capital Territory. Data from individual models were compared highlighting generic elements, and formed the basis for the development of the scope of practice for the Australian Capital Territory nurse practitioner models.

Conclusions. This study has validated a research-based, iterative process for initial development of nurse practitioner scope of practice for any Australian specialization. Importantly, the study concluded with the scope of practice as a finding, rather than commencing with it a priori. Although general areas of health care need and under-servicing were identified at the outset, the process tested both the expansion and parameters of the roles.

Best practice in stabilisation of oral endotracheal tubes : a systematic review

Mechanical ventilation of patients in intensive care units is common practice. Artificial airways are utilised to facilitate ventilation and the endotracheal tube (ETT) is most commonly used for this purpose. The ETT must be stabilised to optimise ventilation and avoid displacement or unplanned extubation. Tube movement is a major factor in causing airway trauma. A destabilised tube can cause fatal complications. A systematic review was conducted to identify and analyse the best available evidence on ETT stabilisation to determine which stabilisation method resulted in reduced tube displacement and the least amount of unplanned or accidental extubations. The types of stabilisations included one or a combination of the following methods: twill or cotton tape, adhesive tape, gauze, or a manufactured device. All relevant randomised controlled and quasi-experimental studies of ETT stabilisation practices, identified through electronic and hand searching, were assessed for inclusion in the study. One published randomised controlled trial and six published quasi-experimental studies met the inclusion and exclusion criteria and were retrieved. Data were extracted independently by two reviewers. Results of the systematic review showed that no single method of ETT stabilisation could be identified as superior for minimising tube displacement and unplanned or accidental extubations. Rigorous randomised controlled trials with clearly identified and described ETT stabilisation methods are required to establish best practice. In addition, comparative research to evaluate cost effectiveness and nursing time requirements would also be of significant benefit to critical care nursing practice.

Quantitative microbial risk assessment models for consumption of raw vegetables irrigated with reclaimed water

Quantitative microbial risk assessment models for estimating the annual risk of enteric virus infection associated with consuming raw vegetables that have been overhead irrigated with nondisinfected secondary treated reclaimed water were constructed. We ran models for several different scenarios of crop type, viral concentration in effluent, and time since last irrigation event. The mean annual risk of infection was always less for cucumber than for broccoli, cabbage, or lettuce. Across the various crops, effluent qualities, and viral decay rates considered, the annual risk of infection ranged from 10–3 to 10–1 when reclaimed-water irrigation ceased 1 day before harvest and from 10–9 to 10–3 when it ceased 2 weeks before harvest. Two previously published decay coefficients were used to describe the die-off of viruses in the environment. For all combinations of crop type and effluent quality, application of the more aggressive decay coefficient led to annual risks of infection that satisfied the commonly propounded benchmark of ≤10–4, i.e., one infection or less per 10,000 people per year, providing that 14 days had elapsed since irrigation with reclaimed water. Conversely, this benchmark was not attained for any combination of crop and water quality when this withholding period was 1 day. The lower decay rate conferred markedly less protection, with broccoli and cucumber being the only crops satisfying the 10–4 standard for all water qualities after a 14-day withholding period. Sensitivity analyses on the models revealed that in nearly all cases, variation in the amount of produce consumed had the most significant effect on the total uncertainty surrounding the estimate of annual infection risk. The models presented cover what would generally be considered to be worst-case scenarios: overhead irrigation and consumption of vegetables raw. Practices such as subsurface, furrow, or drip irrigation and postharvest washing/disinfection and food preparation could substantially lower risks and need to be considered in future models, particularly for developed nations where these extra risk reduction measures are more common.

Pressure injury: an exploration of the relationship between risk factors and interface pressure

Pressure injuries are a serious risk for patients admitted to hospital and are thought to result from a number of forces operating on skin tissue (pressure, shear and friction). Most research on interface pressure (IP) has taken place using healthy volunteers or mannequins. Little is currently known about the relationship between pressure injury risk and IP for hospital patients. This relationship was investigated with a sample of 121 adult hospital patients. Pressure injury risk was evaluated using the Waterlow Risk Assessment Tool (WRAT) and IP was measured at the sacrum using a Tekscan ClinSeatTM IP sensor mat. Other factors considered were body mass index (BMI), blood pressure, reason for hospital admission, comorbidities and admission route to hospital. Patients were classified according to WRAT categories (‘low risk’, ‘at risk’, ‘high risk’, ‘very high risk’) and then remained still on a standard hospital mattress for 10 minutes while IP was measured. Participants in the ‘low risk’ group were significantly younger than all other groups (p<0.001) and there were some group differences in BMI. IP readings were compared between the ‘low risk’ group and all of the participants at greater risk. The ‘low risk’ group had significantly lower IP at the sacrum on a standard hospital mattress than those at greater risk (p=0.002). Those at greater risk tended to have IP readings at the low end of the compromised IP range. This study is significant because it describes a new, clinically relevant methodology and presents findings that challenge clinician assumptions about the relationships between pressure injury risk assessment and IP.

Testosterone replacement therapy-perceptions of recipients and partners

Background. The androgenic hormones are important determinants of sexual behaviour in men. Testosterone replacement is important treatment for pituitary disease to maintain normal functioning. Although the physical effects of testosterone replacement have been well documented, little is known about the effects on relationships, particularly from the point of view of the sexual partners of men receiving testosterone replacement.

Aims. This paper reports a study exploring the perceptions of testosterone replacement on well-being and sexual functioning.

Methods. Semi-structured interviews were conducted with five men receiving testosterone implants (recipients), their permanent partners, and five recipients without partners. Recipient serum testosterone concentration was measured at 0, 1 and 4 months after testosterone implantation.

Results. The three groups reported similar effects of testosterone on well-being and sexual functioning. Recipient and partner ratings were also similar. Strength was less affected by decreasing testosterone concentration than energy in men with partners, but both strength and energy declined in men without partners. Decreased testosterone levels had a statistically significantly different effect on libido at time zero between men with and without partners (P < 0·015) and on ability to sustain an erection, but the ability to achieve an erection persisted over the 6 months in both male groups. Intercourse frequency increased from once per week at time 0 to ≥3 per week between 1 and 4 months after implant in men with partners. There were important effects of testosterone deficiency on general and sexual relationships, and these differed between men with partners and those without.

Conclusions. Testosterone has important physical and psychological benefits that may be related to the age at which testosterone replacement commences and the indications for its use. The small sample size may limit the ability to generalize the findings outside the study.

QuickTime multi-track theatricks

Digital media, corporate database applications and intranets provide efficient ways to create, store and deliver information and educational services. However some academics perceive new workload and other constraints eroding the potency of these technologies. Proposed corporate level information management systems for digital objects and their metadata are new complexities entering academicsÕ thoughts about using online multimedia.

Few staff understand digital multimedia concepts and fewer still, the systems designed to deal with IP management, copyright law compliance and the tracking of digital resource creation processes. Faltering staff enthusiasm warns of their need to experience working models and tangible benefits from these new directions. A project in Deakin's Faculty of Education provides a case study showing how QuickTime is helping academics understand, and increase their use of, multimedia in e-learning environments with an integrated library of digital resources with metadata.

We also report our experience of QuickTime in creating interactive learning objects using multi-tracks. We discuss our idea of theatricks as a performance drawcard - people will come! There is orchestration of multimedia and QuickTime conducts the events, its flexible functionalities providing a safer development environment for solving problems and grasping opportunities.

While difficult for some academics to comprehend, scripting automation and database connectivity through intelligent interfaces might facilitate QuickTime's use in building integrated learning environments with academics. These ideas are considered in relation to staff development, central to the case study project.