Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells

The behaviour of cells cultured within three-dimensional (3D) structures rather than onto two-dimensional (2D) culture plastic more closely reflects their in vivo responses. Consequently, 3D culture systems are becoming crucial scientific tools in cancer cell research. We used a novel 3D culture concept to assess cell-matrix interactions implicated in carcinogenesis: a synthetic hydrogel matrix equipped with key biomimetic features, namely incorporated cell integrin-binding motifs (e.g. RGD peptides) and the ability of being degraded by cell-secreted proteases (e.g. matrix metalloproteases). As a cell model, we chose epithelial ovarian cancer, an aggressive disease typically diagnosed at an advanced stage when chemoresistance occurs. Both cell lines used (OV-MZ-6, SKOV-3) proliferated similarly in 2D, but not in 3D. Spheroid formation was observed exclusively in 3D when cells were embedded within hydrogels. By exploiting the design flexibility of the hydrogel characteristics, we showed that proliferation in 3D was dependent on cell-integrin engagement and the ability of cells to proteolytically remodel their extracellular microenvironment. Higher survival rates after exposure to the anti-cancer drug paclitaxel were observed in cell spheroids grown in hydrogels (40-60%) compared to cell monolayers in 2D (20%). Thus, 2D evaluation of chemosensitivity may not reflect pathophysiological events seen in patients. Because of the design flexibility of their characteristics and their stability in long-term cultures (28 days), these biomimetic hydrogels represent alternative culture systems for the increasing demand in cancer research for more versatile, physiologically relevant and reproducible 3D matrices.

Identifying child sexual abuse within school contexts : policy problems and solutions, and a landmark case

As a strategy to identify child sexual abuse, most Australian States and Territories have enacted legislation requiring teachers to report suspected cases. Some Australian State and non-State educational authorities have also created policy-based obligations to report suspected child sexual abuse. Significantly, these can be wider than non-existent or limited legislative duties, and therefore are a crucial element of the effort to identify sexual abuse. Yet, no research has explored the existence and nature of these policy-based duties. The first purpose of this paper is to report the results of a three-State study into policy-based reporting duties in State and non-State schools in Australia. In an extraordinary coincidence, while conducting the study, a case of failure to comply with reporting policy occurred with tragic consequences. This led to a rare example in Australia (and one of only a few worldwide) of a professional being prosecuted for failure to comply with a legislative duty. It also led to disciplinary proceedings against school staff. The second purpose of this paper is to describe this case and connect it with findings from our policy analysis.

Unraveling the complexity of driving while intoxicated: a study into the prevalence of psychiatric and substance abuse comorbidity

Objective Research is beginning to provide an indication of the co-occurring substance abuse and mental health needs for the driving under the influence (DUI) population. This study aimed to examine the extent of such psychiatric problems among a large sample size of DUI offenders entering treatment in Texas. Methods This is a study of 36,373 past year DUI clients and 308,714 non-past year DUI clients admitted to Texas treatment programs between 2005 and 2008. Data were obtained from the State's administrative dataset. Results Analysis indicated that non-past year DUI clients were more likely to present with more severe illicit substance use problems, while past year DUI clients were more likely to have a primary problem with alcohol. Nevertheless, a cannabis use problem was also found to be significantly associated with DUI recidivism in the last year. In regards to mental health status, a major finding was that depression was the most common psychiatric condition reported by DUI clients, including those with more than one DUI offence in the past year. This cohort also reported elevated levels of Bipolar Disorder compared to the general population, and such a diagnosis was also associated with an increased likelihood of not completing treatment. Additionally, female clients were more likely to be diagnosed with mental health problems than males, as well as more likely to be placed on medications at admission and more likely to have problems with methamphetamine, cocaine, and opiates. Conclusions DUI offenders are at an increased risk of experiencing comorbid psychiatric disorders, and thus, corresponding treatment programs need to cater for a range of mental health concerns that are likely to affect recidivism rates.