Altering the redox state of skeletal muscle by glutathione depletion increases the exercise-activation of PGC-1α

We investigated the relationship between mitochondrial biogenesis, cell signalling and antioxidant enzymes by depleting skeletal muscle glutathione with diethyl maleate (DEM) which resulted in a demonstrable increase in oxidative stress during exercise. Animals were divided into six groups: (1) sedentary control rats; (2) sedentary rats treated with DEM; (3) exercise control rats euthanized immediately after exercise; (4) exercise rats + DEM; (5) exercise control rats euthanized 4 h after exercise, and; (6) exercise rats + DEM euthanized 4 h after exercise. Exercising animals ran on the treadmill at a 10% gradient at 20 m/min for the first 30 min. The speed was then increased every 10 min by 1.6 m/min until exhaustion. There was a reduction in total glutathione in the skeletal muscle of DEM treated animals compared to the control animals (P<0.05). Within the control group, total glutathione was higher in the sedentary group compared to after exercise (P<0.05). DEM treatment also significantly increased oxidative stress, as measured by increased plasma F2-isoprostanes (P<0.05). Exercising animals given DEM showed a significantly greater increase in peroxisome proliferator activated receptor γ coactivator-1α(PGC-1α) mRNA compared to the control animals that were exercised (P<0.05). This study provides novel evidence that by reducing the endogenous antioxidant glutathione in skeletal muscle and inducing oxidative stress through exercise, PGC-1α gene expression was augmented. These findings further highlight the important role of exercise induced oxidative stress in the regulation of mitochondrial biogenesis.

Methotrexate-conjugated PEGylated dendrimers show differential patterns of deposition and activity in tumour-burdened lymph nodes after intravenous and subcutaneous administration in rats

The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumour-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumour growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumour-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumour activity, possibly suggesting constrained drug release at the site of action.

Facilitating lifestyle changes to manage menopausal symptoms in women with breast cancer: A randomized controlled pilot trial of The Pink Women’s Wellness Program

OBJECTIVE Women diagnosed as having breast cancer may experience difficulties with posttreatment effects such as menopausal symptoms. The aims of this pilot study were to (1) evaluate the impact of a multimodal lifestyle program on reducing menopausal symptoms in women with breast cancer and (2) examine the impact of the program on health-related quality of life (HRQoL) and adherence to lifestyle recommendations. METHODS Overall, 55 women aged 45 to 60 years with one moderate to severe menopausal symptom and a history of breast cancer were randomized into an intervention group (n = 26) or a control group (n = 29). Women in the intervention group received a lifestyle intervention (The Pink Women’s Wellness Program) that included clinical consultations and a tailored health education program. Measurements of menopausal symptoms (Greene Climacteric Scale), HRQoL (SF-12 and Functional Assessment of Cancer Therapy—Breast), and modifiable lifestyle factors (food intake, physical activity, smoking and alcohol use, and sleep disturbance) were taken at baseline and 12 weeks. RESULTS Women in the intervention group reported clinically significant reductions in many menopausal symptoms, specifically somatic symptoms (d = 0.52), vasomotor symptoms (d = 0.55), sexual dysfunction (d = .65), and overall menopausal symptoms (d = 0.54), at 12 weeks compared with the control group (d = 0.03, d = 0.24, d = 0.18, and d = 0.05, respectively). Women in the intervention group reported improvements in Functional Assessment of Cancer Therapy—Breast subscale scores, physical well-being and functional well-being, and Functional Assessment of Cancer Therapy—General total scores (intervention group: d = 0.54, d = 0.50, and d = 0.48, respectively; control group: d = 0.22, d = 0.11, and d = 0.05, respectively). CONCLUSIONS The Pink Women’s Wellness Program is effective in decreasing menopausal symptoms, thus improving HRQoL. This being a pilot study, further research is recommended to investigate the benefits of combining nonpharmacological interventions for women with breast cancer to reduce their treatment-related menopausal symptoms.

Decreasing menopausal symptoms in women undertaking a web-based multi-modal lifestyle intervention: The Women's Wellness Program

Menopausal transition can be challenging for many women. This study tested the effectiveness of an intervention delivered in different modes in decreasing menopausal symptoms in midlife women. The Women's Wellness Program (WWP) intervention was delivered to 225 Australian women aged between 40 and 65 years through three modes (i.e., on-line independent, face-to-face with nurse consultations, and on-line with virtual nurse consultations). All women in the study were provided with a 12-week Program Book outlining healthy lifestyle behaviors while women in the consultation groups were supported by a registered nurse who provide tailored health education and assisted with individual goal setting for exercise, healthy eating, smoking and alcohol consumption. Pre- and post-intervention data were collected on menopausal symptoms (Greene Climacteric Scale), health related quality of life (SF12), and modifiable lifestyle factors. Linear mixed-effect models showed an average 0.87 and 1.23 point reduction in anxiety (p < 0.01) and depression scores (p < 0.01) over time in all groups. Results also demonstrated reduced vasomotor symptoms (β = −0.19, SE = 0.10, p = 0.04) and sexual dysfunction (β = −0.17, SE = 0.06, p < 0.01) in all participants though women in the face-to-face group generally reported greater reductions than women in the other groups. This lifestyle intervention embedded within a wellness framework has the potential to reduce menopausal symptoms and improve quality of life in midlife women thus potentially enhancing health and well-being in women as they age. Of course, study replication is needed to confirm the intervention effects.

A hierarchical model of social marketing

Purpose This paper aims to set out a new hierarchical and differentiated model of social marketing principles, concepts and techniques that builds on, but supersedes, the existing lists of non-equivalent and undifferentiated benchmark criteria. Design/methodology/approach This is a conceptual paper that proposes a hierarchical model of social marketing principles, concepts and techniques. Findings This new delineation of the social marketing principle, its four core concepts and five techniques, represents a new way to conceptualize and recognize the different elements that constitute social marketing. This new model will help add to and further the development of the theoretical basis of social marketing, building on the definitional work led by the International Social Marketing Association (iSMA), Australian Association of Social Marketing (AASM) and European Social Marketing Association (ESMA). Research limitations/implications This proposed model offers a foundation for future research to expand upon. Further research is recommended to empirically test the proposed model. Originality/value This paper seeks to advance the theoretical base of social marketing by making a reasoned case for the need to differentiate between principles, concepts and techniques when seeking to describe social marketing.

Cold water immersion: Practices, trends and avenues of effect

Cold water immersion and ice baths are popular methods of recovery used by athletes. From the simple wheelie bin with water and ice, to the inflatable baths with complex water cooling units to recovery sessions in the ocean, the practice of cold water immersion is wide and varied. Research into cold water immersion was conducted as early as 1963 when Clarke1 examined the influence of cold water on performance recovery after a sustained handgrip exercise. Research has been conducted to understand how cold water immersion might affect the body’s physiological systems and how factors such as water temperature and the duration of immersion might enhance recovery after training and/or competition. Despite this research activity, how are we to know if research is being put into practice? In more serious situations, where guidelines and policies need to be standardised for the safe use of a product, one would expect that there is a straight forward follow-on from research into practice. Although cold water immersion may not need the rigor of testing compared to drug treatments, for example, the decision on whether to use cold water immersion in specific situations (e.g. after training or competition) may rest with one or two of the staff associated with the athlete/team. Therefore, it would be expected that these staff are well-informed on the current literature regarding cold water immersion.

Rediscovering law students as citizens: Critical thinking and the public value of legal education

In a series of publications over the last decade, Australian National University Professor Margaret Thornton has documented a disturbing change in the nature of legal education. This body of work culminates in a recently published book based on interviews with 145 legal academics in Australia, the United Kingdom, New Zealand and Canada. In it, Thornton describes a feeling of widespread unease among legal academics that society, government, university administrators and students themselves are moving away from viewing legal education as a public good which benefits both students and society. Instead, legal education is increasingly being viewed as a purely private good, for consumption by the student in the quest for individual career enhancement.

"Unruly women and semiotic spaces": Jay Verney's a mortality tale

Written at a time of significant changes for women and for women writers in Queensland, Australia, Jay Verney's A Mortality Tale (1994), privileges women's experiences of place and seeks to redeem the feminine from its entrapment in masculine stories/discourses of self and place. This chapter draws on Julia Kristeva's conceptualisation of the semiotic as a way of reading Verney's witty and reflective re-articulation of phallocentric orderings of spatiality and gender.

Post-exercise cold water immersion attenuates acute anabolic signalling and long-term adaptations in muscle to strength training

We investigated functional, morphological and molecular adaptations to strength training exercise and cold water immersion (CWI) through two separate studies. In one study, 21 physically active men strength trained for 12 weeks (2 d⋅wk–1), with either 10 min of CWI or active recovery (ACT) after each training session. Strength and muscle mass increased more in the ACT group than in the CWI group (P<0.05). Isokinetic work (19%), type II muscle fibre cross-sectional area (17%) and the number of myonuclei per fibre (26%) increased in the ACT group (all P<0.05) but not the CWI group. In another study, nine active men performed a bout of single-leg strength exercises on separate days, followed by CWI or ACT. Muscle biopsies were collected before and 2, 24 and 48 h after exercise. The number of satellite cells expressing neural cell adhesion molecule (NCAM) (10−30%) and paired box protein (Pax7)(20−50%) increased 24–48 h after exercise with ACT. The number of NCAM+ satellitecells increased 48 h after exercise with CWI. NCAM+- and Pax7+-positivesatellite cell numbers were greater after ACT than after CWI (P<0.05). Phosphorylation of p70S6 kinaseThr421/Ser424 increased after exercise in both conditions but was greater after ACT (P<0.05). These data suggest that CWI attenuates the acute changes in satellite cell numbers and activity of kinases that regulate muscle hypertrophy, which may translate to smaller long-term training gains in muscle strength and hypertrophy. The use of CWI as a regular post-exercise recovery strategy should be reconsidered.

Effects of cold water immersion and active recovery on hemodynamics and recovery of muscle strength following resistance exercise

Cold water immersion (CWI) and active recovery (ACT) are frequently used as post-exercise recovery strategies. However, the physiological effects of CWI and ACT after resistance exercise are not well characterized. We examined the effects of CWI and ACT on cardiac output (Q), muscle oxygenation (SmO2) and blood volume (tHb), muscle temperature (Tmuscle ) and isometric strength after resistance exercise. On separate days, 10 men performed resistance exercise, followed by 10 min CWI at 10°C or 10 min ACT (low-intensity cycling). Q (7.9±2.7 l) and Tmuscle (2.2±0.8ºC) increased, whereas SmO2 (-21.5±8.8%) and tHb (-10.1±7.7 μM) decreased after exercise (p<0.05). During CWI, Q ̇(-1.1±0.7 l) and Tmuscle (-6.6±5.3ºC) decreased, while tHb (121±77 μM) increased (p<0.05). In the hour after CWI, Q ̇and Tmuscle remained low, while tHb also decreased (p<0.05). By contrast, during ACT, Q ̇(3.9±2.3 l), Tmuscle (2.2±0.5ºC), SmO2 (17.1±5.7%) and tHb (91±66 μM) all increased (p<0.05). In the hour after ACT, Tmuscle and tHb remained high (p<0.05). Peak isometric strength during 10 s maximum voluntary contractions (MVCs) did not change significantly after CWI, whereas it decreased after ACT (-30 to -45 Nm; p<0.05). Muscle deoxygenation time during MVCs increased after ACT (p<0.05), but not after CWI. Muscle reoxygenation time after MVCs tended to increase after CWI (p=0.052). These findings suggest firstly that hemodynamics and muscle temperature after resistance exercise are dependent on ambient temperature and metabolic demands with skeletal muscle, and secondly, that recovery of strength after resistance exercise is independent of changes in hemodynamics and muscle temperature.

Targeting ASCT2-mediated glutamine uptake blocks prostate cancer growth and tumour development

Glutamine is conditionally essential in cancer cells, being utilized as a carbon and nitrogen source for macromolecule production, as well as for anaplerotic reactions fuelling the tricarboxylic acid (TCA) cycle. In this study, we demonstrated that the glutamine transporter ASCT2 (SLC1A5) is highly expressed in prostate cancer patient samples. Using LNCaP and PC-3 prostate cancer cell lines, we showed that chemical or shRNA-mediated inhibition of ASCT2 function in vitro decreases glutamine uptake, cell cycle progression through E2F transcription factors, mTORC1 pathway activation and cell growth. Chemical inhibition also reduces basal oxygen consumption and fatty acid synthesis, showing that downstream metabolic function is reliant on ASCT2-mediated glutamine uptake. Furthermore, shRNA knockdown of ASCT2 in PC-3 cell xenografts significantly inhibits tumour growth and metastasis in vivo, associated with the down-regulation of E2F cell cycle pathway proteins. In conclusion, ASCT2-mediated glutamine uptake is essential for multiple pathways regulating the cell cycle and cell growth, and is therefore a putative therapeutic target in prostate cancer.

Endogenous and exogenous effects in self-exciting process models of terrorist activity

A model based on the cluster process representation of the self-exciting process model in White and Porter 2013 and Ruggeri and Soyer 2008is derived to allow for variation in the excitation effects for terrorist events in a self-exciting or cluster process model. The details of the model derivation and implementation are given and applied to data from the Global Terrorism Database from 2000–2012. Results are discussed in terms of practical interpretation along with implications for a theoretical model paralleling existing criminological theory.

Buckling behaviour and design of tapered steel lighting masts

Tapered tubular steel masts are commonly used to support floodlights in a range of applications. The design of these slender tapered masts requires a rational elastic flexural buckling analysis as the thickness also varies with height. Therefore a series of finite element analyses of tapered masts with varying geometry parameters was conducted to develop an elastic flexural buckling load formula. This paper briefly discusses the design methods, and then presents the details of the finite element analyses and the results. 1–Associate Professor of Civil Engineering, and Director, Physical Infrastructure Centre 2–Former BE (Civil) Student, QUT

Internationalizing school curriculum in Australasia: As niche, by test, or at heart?

Global citizenship has emerged as a pressing curricular priority which all educational systems are currently grappling with. The challenge is to negotiate how this orientation might sit alongside the more traditional mission of mass school curriculum in building collective ballast for a national identity through a common morality and shared narratives, or may conflict with efforts to protect and promote indigenous and minority identities. As a case study of how these agendas interact, this chapter will consider curricular responses to global imperatives in the variegated conditions across the Australasian region (defined as Australia, New Zealand and Papua New Guinea). The chapter will outline recent developments in the social, economic and political contexts surrounding curricular reforms in these settings, and demonstrate how these developments have changed the conditions of possibility and strength of purpose behind efforts to internationalise school curricula. Three types of systemic responses are then described: firstly, an appetite for globally branded curricula such as the International Baccalaureate, Montessori, and Cambridge University Certificates to distinguish some in a stratified market; secondly, convergence in curriculum to improve national performance on international standardised tests; and thirdly, the infusion of cosmopolitan sensibilities, regional identities and intercultural competencies as a core curricular goal for all. The chapter considers the various pragmatic interpretations of ‘internationalisation’ in these responses, and argues that the third response seems both the most difficult to enact, and the most vulnerable to political interference.

Proposed vehicle impact speed: Severe injury probability relationships for selected crash types

Speed is recognised as a key contributor to crash likelihood and severity, and to road safety performance in general. Its fundamental role has been recognised by making Safe Speeds one of the four pillars of the Safe System. In this context, impact speeds above which humans are likely to sustain fatal injuries have been accepted as a reference in many Safe System infrastructure policy and planning discussions. To date, there have been no proposed relationships for impact speeds above which humans are likely to sustain fatal or serious (severe) injury, a more relevant Safe System measure. A research project on Safe System intersection design required a critical review of published literature on the relationship between impact speed and probability of injury. This has led to a number of questions being raised about the origins, accuracy and appropriateness of the currently accepted impact speed–fatality probability relationships (Wramborg 2005) in many policy documents. The literature review identified alternative, more recent and more precise relationships derived from the US crash reconstruction databases (NASS/CDS). The paper proposes for discussion a set of alternative relationships between vehicle impact speed and probability of MAIS3+ (fatal and serious) injury for selected common crash types. Proposed Safe System critical impact speed values are also proposed for use in road infrastructure assessment. The paper presents the methodology and assumptions used in developing these relationships. It identifies further research needed to confirm and refine these relationships. Such relationships would form valuable inputs into future road safety policies in Australia and New Zealand.