Induction of epithelial to mesenchymal transition in PMC42-LA human breast carcinoma cells by carcinoma-associated fibroblast secreted factors

Background
Breast carcinoma is accompanied by changes in the acellular and cellular components of the microenvironment, the latter typified by a switch from fibroblasts to myofibroblasts.


Methods
We utilised conditioned media cultures, Western blot analysis and immunocytochemistry to investigate the differential effects of normal mammary fibroblasts (NMFs) and mammary cancer-associated fibroblasts (CAFs) on the phenotype and behaviour of PMC42-LA breast cancer cells. NMFs were obtained from a mammary gland at reduction mammoplasty, and CAFs from a mammary carcinoma after resection.


Results
We found greater expression of myofibroblastic markers in CAFs than in NMFs. Medium from both CAFs and NMFs induced novel expression of α-smooth muscle actin and cytokeratin-14 in PMC42-LA organoids. However, although conditioned media from NMFs resulted in distribution of vimentin-positive cells to the periphery of PMC42-LA organoids, this was not seen with CAF-conditioned medium. Upregulation of vimentin was accompanied by a mis-localization of E-cadherin, suggesting a loss of adhesive function. This was confirmed by visualizing the change in active β-catenin, localized to the cell junctions in control cells/cells in NMF-conditioned medium, to inactive β-catenin, localized to nuclei and cytoplasm in cells in CAF-conditioned medium.


Conclusion
We found no significant difference between the influences of NMFs and CAFs on PMC42-LA cell proliferation, viability, or apoptosis; significantly, we demonstrated a role for CAFs, but not for NMFs, in increasing the migratory ability of PMC42-LA cells. By concentrating NMF-conditioned media, we demonstrated the presence of factor(s) that induce epithelial-mesenchymal transition in NMF-conditioned media that are present at higher levels in CAF-conditioned media. Our in vitro results are consistent with observations in vivo showing that alterations in stroma influence the phenotype and behaviour of surrounding cells and provide evidence for a role for CAFs in stimulating cancer progression via an epithelial-mesenchymal transition. These findings have implications for our understanding of the roles of signalling between epithelial and stromal cells in the development and progression of mammary carcinoma.

A longitudinal study of risk and protective factors associated with successful transition to secondary school in youth with ADHD: prospective cohort study protocol

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) has a significant impact on child and adolescent development, especially in relation to school functioning and academic outcomes. Despite the transition to high school being a potentially critical period for children with ADHD, most research in this period has focused on academic outcomes. This study aims to extend previous research by describing academic, school engagement, behaviour and social-emotional outcomes for young people with ADHD in the first and third years of high school and to identify risk and protective factors predictive of differing outcomes across these four domains. METHODS AND DESIGN: The Moving Up study is a longitudinal, prospective cohort study of children with ADHD as they transition and adjust to high school (age 12-15 years). Data are collected through direct assessment and child, parent and teacher surveys. The primary outcome is academic achievement, obtained by linking to standardised test results. Secondary outcomes include measures of behaviour, ADHD symptoms, school engagement (attitudes and attendance), and social and emotional functioning, including depressive symptoms. The mean performance of the study cohort on each outcome measure will be compared to the population mean for same aged children, using t-tests. Risk and protective factors to be examined using multiple regression include a child, family and school factors know to impact academic and school functioning. DISCUSSION: The Moving up study is the first Australian study prospectively designed to measure a broad range of student outcomes for children with ADHD during the high school transition period. Examining both current (cross sectional) and earlier childhood (longitudinal) factors gives us the potential to learn more about risk and protective factors associated with school functioning in young people with ADHD. The richness and depth of this information could lead to more targeted and effective interventions that may alter academic and wellbeing trajectories for young people at risk of poor outcomes. The study is approved by The Royal Children's Hospital Melbourne Human Research Ethics Committee (33206). Findings will be disseminated through peer-reviewed journals and conference presentations.

Organizational factors in the diffusion of an industry standard: implementing an online documentation system for Australian exporters

At present, governments in many countries are actively engaged in the development of electronic trading and certification standards to enable the smooth operation of export markets. Standards and their usability underpin confidence in the operations of markets and their effective functioning. In institutional markets, an important role for government agencies lies in developing the initial specifications for standards for interoperable systems. Once these specifications are accepted, governments can then facilitate the eventual diffusion of a standard to the B2B marketplace. Acceptance of an industry standard can determine demand, which defines the viability of that market. In this paper, we describe an initiative by a government agency, the Australian Quarantine and Inspection Service (AQIS), in developing EXDOC, a standard for export documentation and the role that AQIS played in its implementation and diffusion. Our case study illustrates a successfully facilitated B2G implementation. It demonstrates how a standard can be supported and promulgated for the effective functioning of markets in the transition from manual to online export documentation. Once the overarching specifications for related industries have been established and diffused by government, opportunities arise for private sector markets to develop across these industries. Government agencies can promote the effective operation of standards for electronic markets. The EXDOC implementation and its iterations provide an exemplar of active engagement in the development of electronic trading and certification standards for an institutional market. Its successful diffusion provides a model of the implementation process for other export sectors and agencies.

Career development year in emergency nursing: using specific educational preparation and clinical support to facilitate the transition to specialist practice

This article outlines the development, implementation and evaluation of the Career Development Year (CDY) in the Emergency Department (ED) at Dandenong Hospital in Victoria, Australia. As a consequence of a shortage of emergency nurses, hospitals have recruited inadequately prepared nurses to staff their EDs. The resultant increase in stress of qualified and experienced emergency nurses has had a major impact on the retention of emergency nurses. The CDY aims to provide nurses with little or no experience in emergency nursing with supported entry into this area of specialist practice. The CDY is based on three factors identified as important in the transition to emergency nursing; knowledge, clinical support and professional development. By providing beginning emergency nurses with supported entry to a new and challenging clinical environment, the CDY has been an effective recruitment and retention strategy. In addition it has demonstrated that a committed ED team has the capability to teach and nurture the emergency nurses of the future.

Project management practice in transition of old residential region

With the rapid urbanisation worldwide, the transitions of old residential regions inside or close to the urban districts have been challenging both governments and professionals. The sustainable maintenance, innovation and construction of these regions incorporate the history, culture, environment and policy factors into the economic objectives. Over the long and complex process of a transition project, the dedicated project management crew are frequently confronted with diversified novel issues and obliged to contribute appropriate solutions urgently. In this paper, the authors first analyse the state of the art of transition projects of old residential regions based on their practices in real projects. Furthermore, the authors explore the sustainable alternatives of transition projects from the reservation and development perspectives of culture, environment, society and infrastructure. Finally, the authors develop a multi-dimensional implementary framework for guiding the practices of management of transition projects.

Women's psychosocial well-being following a major life transition

Some women are devastated by divorce, while others learn from the experience. In-depth interviews with sole-parenting women yielded themes that were then assessed using structured questionnaires. Statistical models showed that psychological adjustment and physical well-being related more strongly to psychological factors, such as sense of coherence, than to situational variables.

Role of internal cognitive processes and external causal attributions in midlife transition

This project was designed to ascertain the defining attributes of midlife that render it distinct from young and older adulthood. Based on the determined salient factors the Midlife Adjustment Scale was developed and the nature of midlife, that of a transitional period, was established. The scale was then used to assess the influence that perceived control and major life events have on one's adjustment during the middle years.

Dynamic mechanical thermal analysis studies of factors influencing relaxation in polyetherurethane based solid electrolytes

Dynamic mechanical thermal analysis (DMTA) has been used to study the effects of plasticizers on the mobility and homogeneity of a series of solid polymer electrolytes (SPEs). With reference to previously published results on similar systems containing LiClO₄ salts and tetraglyme as plasticizer, the effects of propylene carbonate (PC) on the glass transition temperature (T_g) of the SPE and on the distribution of relaxation times within the sample are discussed; at low plasticizer concentration PC has little effect on T_g as measured by DMTA in comparison with tetraglyme, and at higher plasticizer concentrations PC significantly broadens the mechanical relaxation behaviour indicating a greater degree of dynamical heterogeneity within the sample. A second low temperature relaxation is evident at lower PC contents indicating that some regions of this plasticized SPE are distinctly more mobile than others or perhaps, on this length scale, that some degree of phase separation is present. Activation energies for the mechanical relaxation were also determined as a function of PC concentration and are significantly greater than those determined from conductivity measurements.

The relationship between social capital and depression during the transition to adulthood

Relatively high levels of depression are observed during the transition to adulthood. Hence, it is important to identify the factors that can reduce the incidence of depression at this time. Social capital is theorised to protect against depression by providing greater access to support and psychological resources. Social capital incorporates both interpersonal relationships and broader community-level factors. However, most research has focused on the influence of relationships with parents and peers in the development of depression in young people, with little attention given to the role of broader social capital factors relating to perceptions of and engagement with the wider community. Drawing on longitudinal data from the Australian Temperament Project (ATP), this article examines the effects of close interpersonal relationships (with parents and peers) and broader, community-level aspects of social capital (trust and civic engagement) on depression during the transition to adulthood. Using hierarchical multiple regression, alienation from peers was found to predict higher depression, whereas good communication with peers was associated with a reduction of depressive symptoms. After controlling for the effects of close interpersonal relationships, trust in authorities and organisations made a significant contribution to the prediction of lower depression. Implications for intervention are discussed.

Emerging nutritional and lifestyle risk factors for bone health in young women: a mixed longitudinal twin study

Late adolescence and early adulthood are times of major behavioral transition in young women as they become more independent and make choices about lifestyle that will affect their long-term health. We prospectively evaluated nutritional and lifestyle factors in 566 15 30-year-old female twins participating in a mixed longitudinal study of diet and lifestyle.Twins completed 790 visits including questionnaires and measures of anthropometry. Nonparametric tests (chi-square, Mann-Whitney U, and Kruskal-Wallis; SPSS) were used to examine age-related differences in selected variables. Dietary calcium intake by short food frequency questionnaire was relatively low [511 (321,747)] mg/day (median, IQR; 60 % of estimated daily total) and did not vary significantly with age. The number of young women who reported ever consuming alcohol (12+ standard drinks ever) increased from 50 % under 18 years to 93 99 % for the 18+ age groups. Of those who consumed alcohol in the preceding year, monthly intake doubled from under 18 years (5.7, 3.9, 19.0 standard drinks; median, IQR) to 18+ years (12.0, 4.7, 26.0; P < 0.001) with the highest consumers being 21 23 and 27 29 years. At age 15 17 years, 14 % reported ever smoking and by age 27–29, 51 % had smoked (P = 0.002). Under the age of 20 years, average cigarette consumption in smokers was six cigarettes per day, increasing to ten above age 20 (P < 0.001). Participation in sporting activity decreased with age (P < 0.001): 47.5 % of 15–17-year-olds undertook 4 or more hour/week of sport, compared with 23.5 % at age 27–29 years. Conversely, sedentary behavior increased with age: 25.0 % of 15–17-year-olds reported 1 or less hour/week of exercise compared with 50.0 % at age 27–29 years. BMI increased with age (P = 0.011), from 21.3 (19.5, 23.6; median, IQR) in the youngest to 23.1 (21.5, 25.9) in the oldest. These highly significant changes in behavior in young women as they transitioned into independent adult living are predicted to impact adversely on bone and other health outcomes in later life. It is crucial to improve understanding of the determinants of these changes and to develop effective interventions to improve long-term health outcomes in young women.

Pathways to university : enabling factors in construction management education in Australia

Past Australian and international research has shown that many students find transition and navigating pathways from vocational education to university difficult. This paper proposes a framework for evaluating the success of these pathways in construction management education. Students enrolled in undergraduate degree courses responded to a questionnaire on the nature of their experiences in vocational education and how this impacted on their decision to articulate to university. The survey covered a sample of three universities across Australia. The results showed that students generally had positive experiences, but that some pathways had better outcomes than others. Utilising an existing outreach-developed matrix the research identified three factors that were good measures of the success of pathways models. The paper concludes by suggesting that universities need a greater awareness of the impact of transition issues for their pathways students. This research is significant in that it considers pathways as an organised and systematic process, which is capable of being defined and measured.

Stomach temperature records reveal nursing behaviour and transition to solid food consumption in an unweaned mammal, the harbour seal pup (Phoca vitulina)

Knowledge of milk transfer from mother to offspring and early solid food ingestions in mammals allows for a greater understanding of the factors affecting transition to nutritional independence and pre-weaning growth and survival. Yet studies monitoring suckling behaviour have often relied on visual observations, which might not accurately represent milk intake. We assessed the use of stomach temperature telemetry to monitor suckling and foraging behaviour in free-ranging harbour seal (Phoca vitulina) pups during lactation. Stomach temperature declines were analysed using principal component and cluster analyses, as well as trials using simulated stomachs resulting in a precise classification of stomach temperature drops into milk, seawater and solid food ingestions. Seawater and solid food ingestions represented on average 15.361.6% [0-40.0%] and 0.760.2% [0-13.0%], respectively, of individual ingestions. Overall, 63.7% of milk ingestions occurred while the pups were in the water, of which 13.9% were preceded by seawater ingestion. The average time between subsequent ingestions was significantly less for seawater than for milk ingestions. These results suggest that seawater ingestion might represent collateral ingestion during aquatic suckling attempts. Alternatively, as solid food ingestions (n = 19) were observed among 7 pups, seawater ingestion could result from missed prey capture attempts. This study shows that some harbour seals start ingesting prey while still being nursed, indicating that weaning occurs more gradually than previously thought in this species. Stomach temperature telemetry represents a promising method to study suckling behaviour in wild mammals and transition to nutritional independence in various endotherm species.

The transition to motherhood: towards a broader understanding of perinatal distress

A substantial body of research has focused on maternal perinatal mood and wellbeing, with the focus predominantly being on depression, and to a lesser extent, anxiety. Perinatal maternal stress has also been investigated recently, but to a far lesser extent. The present paper questions whether the term 'perinatal distress' accurately captures the range of challenges experienced by women during the perinatal period, when the scope of 'distress' is limited to the experience of depression and anxiety alone.

Satisfaction of newly graduated nurses enrolled in transition-to-practice programmes in their first year of employment: a systematic review

To investigate job satisfaction and confidence levels of graduate nurses during their first year of employment and the impact various training programmes have on these factors.