An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity

Recent evidence indicates that the estrogen receptor-a-negative, androgen receptor (AR)- positive molecular apocrine subtype of breast cancer is driven by AR signaling. The MDA-MB-453 cell line is the prototypical model of this breast cancer subtype; its proliferation is stimulated by androgens such as 5a-dihydrotestosterone (DHT) but inhibited by the progestin medroxyprogesterone acetate (MPA) via AR-mediated mechanisms. We report here that the AR gene in MDAMB- 453 cells contains a G-T transversion in exon 7, resulting in a receptor variant with a glutamine to histidine substitution at amino acid 865 (Q865H) in the ligand binding domain. Compared with wild-type AR, the Q865H variant exhibited reduced sensitivity to DHT and MPA in transactivation assays in MDA-MB-453 and PC-3 cells but did not respond to non-androgenic ligands or receptor antagonists. Ligand binding, molecular modeling, mammalian two-hybrid and immunoblot assays revealed effects of the Q865H mutation on ligand dissociation, AR intramolecular interactions, and receptor stability. Microarray expression profiling demonstrated that DHT and MPA regulate distinct transcriptional programs in MDA-MB-453 cells. Gene Set Enrichment Analysis revealed that DHT- but not MPA-regulated genes were associated with estrogen-responsive transcriptomes from MCF-7 cells and the Wnt signaling pathway. These findings suggest that the divergent proliferative responses of MDA-MB-453 cells to DHT and MPA result from the different genetic programs elicited by these two ligands through the AR-Q865H variant. This work highlights the necessity to characterize additional models of molecular apocrine breast cancer to determine the precise role of AR signaling in this breast cancer subtype. Endocrine-Related Cancer (2012) 19 599–613

Cone signals and activity in myopia and emmetropia

Myopia (short-sightedness) is a common ocular disorder of children and young adults. Studies primarily using animal models have shown that the retina controls eye growth and the outer retina is likely to have a key role. One theory is that the proportion of L (long-wavelength-sensitive) and M (medium-wavelength-sensitive) cones is related to myopia development; with a high L/M cone ratio predisposing individuals to myopia. However, not all dichromats (persons with red-green colour vision deficiency) with extreme L/M cone ratios have high refractive errors. We predict that the L/M cone ratio will vary in individuals with normal trichromatic colour vision but not show a systematic difference simply due to refractive error. The aim of this study was to determine if L/M cone ratios in the central 30° are different between myopic and emmetropic young, colour normal adults. Information about L/M cone ratios was determined using the multifocal visual evoked potential (mfVEP). The mfVEP can be used to measure the response of visual cortex to different visual stimuli. The visual stimuli were generated and measurements performed using the Visual Evoked Response Imaging System (VERIS 5.1). The mfVEP was measured when the L and M cone systems were separately stimulated using the method of silent substitution. The method of silent substitution alters the output of three primary lights, each with physically different spectral distributions to control the excitation of one or more photoreceptor classes without changing the excitation of the unmodulated photoreceptor classes. The stimulus was a dartboard array subtending 30° horizontally and 30° vertically on a calibrated LCD screen. The m-sequence of the stimulus was 215-1. The N1-P1 amplitude ratio of the mfVEP was used to estimate the L/M cone ratio. Data were collected for 30 young adults (22 to 33 years of age), consisting of 10 emmetropes (+0.3±0.4 D) and 20 myopes (–3.4±1.7 D). The stimulus and analysis techniques were confirmed using responses of two dichromats. For the entire participant group, the estimated central L/M cone ratios ranged from 0.56 to 1.80 in the central 3°-13° diameter ring and from 0.94 to 1.91 in the more peripheral 13°-30° diameter ring. Within 3°-13°, the mean L/M cone ratio of the emmetropic group was 1.20±0.33 and the mean was similar, 1.20±0.26, for the myopic group. For the 13°-30° ring, the mean L/M cone ratio of the emmetropic group was 1.48±0.27 and it was slightly lower in the myopic group, 1.30±0.27. Independent-samples t-test indicated no significant difference between the L/M cone ratios of the emmetropic and myopic group for either the central 3°-13° ring (p=0.986) or the more peripheral 13°-30° ring (p=0.108). The similar distributions of estimated L/M cone ratios in the sample of emmetropes and myopes indicates that there is likely to be no association between the L/M cone ratio and refractive error in humans.

An activity and resource advisory system for manufacturing process chains selection at the early stage of product development

Designers need to consider both the functional and production process requirements at the early stage of product development. A variety of the research works found in the literature has been proposed to assist designers in selecting the most viable manufacturing process chain. However, they do not provide any assistance for designers to evaluate the processes according to the particular circumstances of their company. This paper describes a framework of an Activity and Resource Advisory System (ARAS) that generates advice about the required activities and the possible resources for various manufacturing process chains. The system provides more insight, more flexibility, and a more holistic and suitable approach for designers to evaluate and then select the most viable manufacturing process chain at the early stage of product development.

Does activity in computer game play have an impact on creative behavior?

This paper describes a behaviour analysis designed to measure the creative potential of computer game activities. The research approach applies a behavioural and verbal protocol to analyze the factors that influence the creative processes used by people as they play computer games from the puzzle genre. Creative components are measured by examining task motivation as well as domain-relevant and creativity-relevant skills factors. This paper focuses on how three puzzle games embody activity that might facilitate creative processes. The findings show that game playing activities significantly impact upon creative potential of computer games.

Contemporary research on parenting: conceptual, methodological, and translational issues.

Researchers over the last decade have documented the association between general parenting style and numerous factors related to childhood obesity (e.g., children's eating behaviors, physical activity, and weight status). Many recent childhood obesity prevention programs are family focused and designed to modify parenting behaviors thought to contribute to childhood obesity risk. This article presents a brief consideration of conceptual, methodological, and translational issues that can inform future research on the role of parenting in childhood obesity. They include: (1) General versus domain specific parenting styles and practices; (2) the role of ethnicity and culture; (3) assessing bidirectional influences; (4) broadening assessments beyond the immediate family; (5) novel approaches to parenting measurement, and; (6) designing effective interventions. Numerous directions for future research are offered.

What do we know about recovery interventions used in the management of delayed onset muscle soreness?

Since the pioneering work of Hough in 1902 (1) the term ‘delayed onset muscle soreness (DOMS)’ has dominated the field of athletic recovery. DOMS typically occurs after exercise induced muscle damage (EIMD), particularly if the exercise is unaccustomed or involves a large amount of eccentric (muscle lengthening) contractions. The symptoms of EIMD manifest as a temporary reduction in muscle force, disturbed proprioceptive acuity, increases in inflammatory markers both within the injured muscle and in the blood as well as increased muscle soreness, stiffness and swelling. The intensity of discomfort and soreness associated with DOMS increases within the first 24 hours, peaks between 24 and 72 hours, before subsiding and eventually disappearing 5-7 days after the exercise. Consequently, DOMS may interfere with athletic training or competition and several recovery interventions have been utilised by athletes and coaches in an attempt to offset the negative effects...

An observational study of nutrition and physical activity behaviours, knowledge, and advice in pregnancy

Maternal obesity, excess weight gain and lifestyle behaviours during pregnancy have been associated with future overweight and other adverse health outcomes for mothers and babies. This study compared the nutrition and physical activity behaviours of Australian healthy (BMI ≤ 25 k/m2) and overweight (BMI ≥ 25 kg/m2) pregnant women and described their knowledge and receipt of health professional advice early in pregnancy. Methods Pregnant women (n=58) aged 29±5 (mean±s.d.) years were recruited at 16±2 weeks gestation from an Australian metropolitan hospital. Height and weight were measured using standard procedures and women completed a self administered semi-quantitative survey. Results Healthy and overweight women had very similar levels of knowledge, behaviour and levels of advice provided except where specifically mentioned. Only 8% and 36% of participants knew the correct recommended daily number of fruit and vegetable serves respectively. Four percent of participants ate the recommended 5 serves/day of vegetables. Overweight women were less likely than healthy weight women to achieve the recommended fruit intake (4% vs. 8%, p=0.05), and more likely to consume soft drinks or cordial (55% vs 43%, p=0.005) and take away foods (37% vs. 25%, p=0.002) once a week or more. Less than half of all women achieved sufficient physical activity. Despite 80% of women saying they would have liked education about nutrition, physical activity and weight gain, particularly at the beginning of pregnancy, less than 50% were given appropriate advice regarding healthy eating and physical activity. Conclusion Healthy pregnancy behaviour recommendations were not being met, with overweight women less likely to meet some of the recommendations. Knowledge of dietary recommendations was poor and health care professional advice was limited. There are opportunities to improve the health care practices and education pregnant women received to improve knowledge and behaviours. Pregnant women appear to want this.

Depression scores predict adherence in a dietary weight loss intervention trial

Background & aims Depression has a complex association with cardiometabolic risk, both directly as an independent factor and indirectly through mediating effects on other risk factors such as BMI, diet, physical activity, and smoking. Since changes to many cardiometabolic risk factors involve behaviour change, the rise in depression prevalence as a major global health issue may present further challenges to long-term behaviour change to reduce such risk. This study investigated associations between depression scores and participation in a community-based weight management intervention trial. Methods A group of 64 overweight (BMI > 27), otherwise healthy adults, were recruited and randomised to follow either their usual diet, or an isocaloric diet in which saturated fat was replaced with monounsaturated fat (MUFA), to a target of 50% total fat, by adding macadamia nuts to the diet. Subjects were assessed for depressive symptoms at baseline and at ten weeks using the Beck Depression Inventory (BDI-II). Both control and intervention groups received advice on National Guidelines for Physical Activity and adhered to the same protocol for food diary completion and trial consultations. Anthropometric and clinical measurements (cholesterol, inflammatory mediators) also were taken at baseline and 10 weeks. Results During the recruitment phase, pre-existing diagnosed major depression was one of a range of reasons for initial exclusion of volunteers from the trial. Amongst enrolled participants, there was a significant correlation (R = −0.38, p < 0.05) between BDI-II scores at baseline and duration of participation in the trial. Subjects with a baseline BDI ≥10 (moderate to severe depression symptoms) were more likely to dropout of the trial before week 10 (p < 0.001). BDI-II scores in the intervention (MUFA) diet group decreased, but increased in the control group over the 10-week period. Univariate analysis of variance confirmed these observations (adjusted R2 = 0.257, p = 0.01). Body weight remained static over the 10-week period in the intervention group, corresponding to a relative increase in the control group (adjusted R2 = 0.097, p = 0.064). Conclusions Depression symptoms have the potential to affect enrolment in and adherence to dietbased risk reduction interventions, and may consequently influence the generalisability of such trials. Depression scores may therefore be useful for characterising, screening and allocating subjects to appropriate treatment pathways.

Using technology to change adult sedentary behaviour, physical activity levels and total wellness

This thesis studied technology’s role in promoting and supporting active lifestyles through behavioural strategies to reduce sedentary time and increase physical activity. The five studies included (1) development of a self-report instrument quantifying daily sedentary behaviour and light-intensity physical activity; (2) establishment of instrument validity and reliability; (3) use of an online personal activity monitor to successfully reduce sedentary time and increase physical activity; (4) identification of positive differences in total wellness as related to high/low levels of sitting time combined with insufficient/sufficient physical activity; and (5) improvement of total wellness through positive changes in sedentary behaviour and physical activity.

Physical activity, sedentary behavior and total wellness changes among sedentary adults : a 4-week randomized controlled trial

Background The construct of total wellness includes a holistic approach to the body, mind and spirit components of life. While the health benefits of reducing sedentary behavior and increasing physical activity are well documented, little is known about the influence on total wellness of an internet-based physical activity monitor designed to help people to achieve higher physical activity levels. Purpose The purpose of this four-week, personal activity monitor-based intervention program was to reduce sedentary behavior and increase physical activity levels in daily living for sedentary adults and to determine if these changes would also be associated with improvement in total wellness. Methods Twenty-two men and 11 women (27 years ± 4.0) were randomly assigned to either an intervention (n = 18) or control group (n = 15). The intervention group interacted with an online personal activity monitor (Gruve Solution™) designed to reduce sedentary time and increase physical activity during activities of daily living. The control group did not interact with the monitor, as they were asked to follow their normal daily physical activities and sedentary behavior routines. The Wellness Evaluation of Lifestyle (WEL) inventory was used to assess total wellness. Sedentary time, light, walking, moderate and vigorous intensity physical activities were assessed for both intervention and control groups at baseline and at week-4 by the 7-day Sedentary and Light Intensity Physical Activity Log (7-day SLIPA Log) and the International Physical Activity Questionnaire (IPAQ). Results Significant increases in pre-post total wellness scores (from 64% ± 5.7 to 75% ± 8.5) (t (17) = -6.5, p < 0.001) were observed in the intervention group by the end of week four. Intervention participants decreased their sedentary time (21%, 2.3 hours/day) and increased their light (36.7%, 2.5 hours/day), walking (65%, 1057 MET-min/week), moderate (67%, 455 MET-min/week) and vigorous intensity (60%, 442 MET-min/week) physical activity (all p < 0.001). No significant differences for total wellness were observed between the groups at baseline and no pre-post significant differences were observed for any outcome variable in the control group. Conclusion Total wellness is improved when sedentary, but sufficiently physically active adults, reduce sedentary time and increase physical activity levels (i.e. light, walking, moderate and vigorous).

Consecutive bouts of diverse contractile activity alter acute responses in human skeletal muscle

We examined acute molecular responses in skeletal muscle to divergent exercise stimuli by combining consecutive bouts of resistance and endurance exercise. Eight men [22.9 ± 6.3 yr, body mass of 73.2 ± 4.5 kg, peak O2 uptake (V?O2peak) of 54.0 ± 5.7 ml·kg-1·min-1] were randomly assigned to complete trials consisting of either resistance exercise (8 x 5 leg extension, 80% 1 repetition maximum) followed by a bout of endurance exercise (30 min cycling, 70% V?O2peak) or vice versa. Muscle biopsies were obtained from the vastus lateralis at rest, 15 min after each exercise bout, and after 3 h of passive recovery to determine early signaling and mRNA responses. Phosphorylation of Akt and Akt1Ser473 were elevated 15 min after resistance exercise compared with cycling, with the greatest increase observed when resistance exercise followed cycling (?55%; P < 0.01). TSC2-mTOR-S6 kinase phosphorylation 15 min after each bout of exercise was similar regardless of the exercise mode. The cumulative effect of combined exercise resulted in disparate mRNA responses. IGF-I mRNA content was reduced when cycling preceded resistance exercise (-42%), whereas muscle ring finger mRNA was elevated when cycling was undertaken after resistance exercise (?52%; P < 0.05). The hexokinase II mRNA level was higher after resistance cycling (?45%; P < 0.05) than after cycling-resistance exercise, whereas modest increases in peroxisome proliferator-activated receptor gamma coactivator-1? mRNA did not reveal an order effect. We conclude that acute responses to diverse bouts of contractile activity are modified by the exercise order. Moreover, undertaking divergent exercise in close proximity influences the acute molecular profile and likely exacerbates acute "interference".

Premonolayer oxidation of nanostructured gold : an important factor influencing electrocatalytic activity

The study of the electrodeposition of polycrystalline gold in aqueous solution is important from the viewpoint that in electrocatalysis applications ill-defined micro- and nanostructured surfaces are often employed. In this work, the morphology of gold was controlled by the electrodeposition potential and the introduction of Pb(CH3COO)2•3H2O into the plating solution to give either smooth or nanostructured gold crystallites or large dendritic structures which have been characterized by scanning electron microscopy (SEM). The latter structures were achieved through a novel in situ galvanic replacement of lead with AuCl4−(aq) during the course of gold electrodeposition. The electrochemical behavior of electrodeposited gold in the double layer region was studied in acidic and alkaline media and related to electrocatalytic performance for the oxidation of hydrogen peroxide and methanol. It was found that electrodeposited gold is a significantly better electrocatalyst than a polished gold electrode; however, performance is highly dependent on the chosen deposition parameters. The fabrication of a deposit with highly active surface states, comparable to those achieved at severely disrupted metal surfaces through thermal and electrochemical methods, does not result in the most effective electrocatalyst. This is due to significant premonolayer oxidation that occurs in the double layer region of the electrodeposited gold. In particular, in alkaline solution, where gold usually shows the most electrocatalytic activity, these active surface states may be overoxidized and inhibit the electrocatalytic reaction. However, the activity and morphology of an electrodeposited film can be tailored whereby electrodeposited gold that exhibits nanostructure within the crystallites on the surface demonstrated enhanced electrocatalytic activity compared to smaller smooth gold crystallites and larger dendritic structures in potential regions well within the double layer region.

Gold nanospikes formed through a simple electrochemical route with high electrocatalytic and surface enhanced Raman scattering activity

We demonstrate a simple electrochemical route to produce uniformly sized gold nanospikes without the need for a capping agent or prior modification of the electrode surface, which are predominantly oriented in the {111} crystal plane and exhibit promising electrocatalytic and SERS properties.

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.

Positive reappraisal improves heart rate variability during stressful work

Recent developments in wearable ECG technology have seen renewed interest in the use of Heart Rate Variability (HRV) feedback for stress management. Yet, little is know about the efficacy of such interventions. Positive reappraisal is an emotion regulation strategy that involves changing the way a situation is construed to decrease emotional impact. We sought to test the effectiveness of an intervention that used feedback on HRV data to prompt positive reappraisal during a stressful work task. Participants (N=122) completed two 20-minute trials of an inbox activity. In-between the first and the second trial participants were assigned to the waitlist control condition, a positive reappraisal via psycho-education condition, or a positive reappraisal via HRV feedback condition. Results revealed that using HRV data to frame a positive reappraisal message is more effective than using psycho-education (or no intervention)–especially for increasing positive mood and reducing arousal.