Reported consumption of takeaway food and its contribution to socioeconomic inequalities in body mass index

The aim of this study was to examine whether takeaway food consumption mediated (explained) the association between socioeconomic position and body mass index (BMI). A postal-survey was conducted among 1500 randomly selected adults aged between 25 and 64 years in Brisbane, Australia during 2009 (response rate 63.7%, N=903). BMI was calculated using self-reported weight and height. Participants reported usual takeaway food consumption, and these takeaway items were categorised into "healthy" and "less healthy" choices. Socioeconomic position was ascertained by education, household income, and occupation. The mean BMI was 27.1kg/m(2) for men and 25.7kg/m(2) for women. Among men, none of the socioeconomic measures were associated with BMI. In contrast, women with diploma/vocational education (β=2.12) and high school only (β=2.60), and those who were white-collar (β=1.55) and blue-collar employees (β=2.83) had significantly greater BMI compared with their more advantaged counterparts. However, household income was not associated with BMI. Among women, the consumption of "less healthy" takeaway food mediated BMI differences between the least and most educated, and between those employed in blue collar occupations and their higher status counterparts. Decreasing the consumption of "less healthy" takeaway options may reduce socioeconomic inequalities in overweight and obesity among women but not men.

Demand response for residential appliances via Customer Reward Scheme

This paper proposes a reward based demand response algorithm for residential customers to shave network peaks. Customer survey information is used to calculate various criteria indices reflecting their priority and flexibility. Criteria indices and sensitivity based house ranking is used for appropriate load selection in the feeder for demand response. Customer Rewards (CR) are paid based on load shift and voltage improvement due to load adjustment. The proposed algorithm can be deployed in residential distribution networks using a two-level hierarchical control scheme. Realistic residential load model consisting of non-controllable and controllable appliances is considered in this study. The effectiveness of the proposed demand response scheme on the annual load growth of the feeder is also investigated. Simulation results show that reduced peak demand, improved network voltage performance, and customer satisfaction can be achieved.

Development and validation of anthropometric prediction equations for estimation of body fat in Indonesian men

Body composition of 292 males aged between 18 and 65 years was measured using the deuterium oxide dilution technique. Participants were divided into development (n=146) and cross-validation (n=146) groups. Stature, body weight, skinfold thickness at eight sites, girth at five sites, and bone breadth at four sites were measured and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-stature ratio (WSR) calculated. Equations were developed using multiple regression analyses with skinfolds, breadth and girth measures, BMI, and other indices as independent variables and percentage body fat (%BF) determined from deuterium dilution technique as the reference. All equations were then tested in the cross-validation group. Results from the reference method were also compared with existing prediction equations by Durnin and Womersley (1974), Davidson et al (2011), and Gurrici et al (1998). The proposed prediction equations were valid in our cross-validation samples with r=0.77- 0.86, bias 0.2-0.5%, and pure error 2.8-3.6%. The strongest was generated from skinfolds with r=0.83, SEE 3.7%, and AIC 377.2. The Durnin and Womersley (1974) and Davidson et al (2011) equations significantly (p<0.001) underestimated %BF by 1.0 and 6.9% respectively, whereas the Gurrici et al (1998) equation significantly (p<0.001) overestimated %BF by 3.3% in our cross-validation samples compared to the reference. Results suggest that the proposed prediction equations are useful in the estimation of %BF in Indonesian men.

Integrin αvβ3 upregulates integrin-linked kinase expression in human ovarian cancer cells via enhancement of ILK gene transcription

We previously showed that integrin alphavbeta3 overexpression and engagement by its ligand vitronectin increased adhesion, motility, and proliferation of human ovarian cancer cells. In search of differentially regulated genes involved in these tumor biological events, we previously identified the integrin-linked kinase (ILK) to be under control of alphavbeta3. In the present investigation we demonstrated significantly upregulated ILK protein as a function of alphavbeta3 in two ovarian cancer cell lines, OV-MZ-6 and OVCAR-3, and proved co-localization at the surface of alphavbeta3-overexpressing cells adherent to vitronectin. Increase of ILK protein was reflected by enhanced ILK promoter activity, an effect, which we further characterized with regard to transcriptional response elements involved. Abrogation of NF-kappaB/c-rel or p53 binding augmented ILK promoter activity and preserved induction by alphavbeta3. The AP1-mutant exhibited decreased promoter activity but was also still inducible by alphavbeta3. Disruption of the two DNA consensus motifs for Ets proteins led to divergent observations: mutation of the Ets motif at promoter position -462 bp did not significantly alter promoter activity but still allowed response to alphavbeta3. In contrast, disruption of the second Ets motif at position -85 bp did not only lead to slightly diminished promoter activity but also, in that case, abrogated ILK promoter induction by alphavbeta3. Subsequent co-transfection studies with ets-1 in the presence of the second Ets motif led to additional induction of ILK promoter activity. Taken together, these data suggest that ets-1 binding to the second Ets DNA motif strongly contributes to alphavbeta3-mediated ILK upregulation. By increasing ILK as an important integrin-proximal kinase, alphavbeta3 may promote its intracellular signaling and tumor biological processes arising thereof in favor of ovarian cancer metastasis.

Integrin αvβ3 mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells

Upon overexpression of integrin αvβ3 and its engagement by vitronectin, we previously showed enhanced adhesion, proliferation, and motility of human ovarian cancer cells. By studying differential expression of genes possibly related to these tumor biological events, we identified the epidermal growth-factor receptor (EGF-R) to be under control of αvβ3 expression levels. Thus in the present study we characterized αvβ3-dependent changes of EGF-R and found significant upregulation of its expression and activity which was reflected by prominent changes of EGF-R promoter activity. Upon disruption of DNA-binding motifs for the transcription factors p53, ETF, the repressor ETR, p50, and c-rel, respectively, we sought to identify DNA elements contributing to αvβ3-mediated EGF-R promoter induction. Both, the p53- and ETF-mutant, while exhibiting considerably lower EGF-R promoter activity than the wild type promoter, retained inducibility by αvβ3. Mutation of the repressor motif ETR, as expected, enhanced EGF-R promoter activity with a further moderate increase upon αvβ3 elevation. The p50-mutant displayed EGF-R promoter activity almost comparable to that of the wild type promoter with no impairment of induction by αvβ3. However, the activity of an EGF-R promoter mutant displaying a disrupted c-rel-binding motif did not only prominently decline, but, moreover, was not longer responsive to enhanced αvβ3, involving this DNA element in αvβ3-dependent EGF-R upregulation. Moreover, αvβ3 did not only increase the EGF-R but, moreover, also led to obvious co-clustering on the cancer cell surface. By studying αvβ3/EGF-R-effects on the focal adhesion kinase (FAK) and the mitogen activated protein kinases (MAPK) p44/42 (erk−1/erk−2), having important functions in synergistic crosstalk between integrins and growth-factor receptors, we found for both significant enhancement of expression and activity upon αvβ3/VN interaction and cell stimulation by EGF. Upregulation of the EGF-R by integrin αvβ3, both receptor molecules with a well-defined role as targets for cancer treatment, might represent an additional mechanism to adapt synergistic receptor signaling and crosstalk in response to an altered tumor cell microenvironment during ovarian cancer progression.

Understanding the abnormal brain activity in epilepsy as a potential predictor of the onset of an epileptic seizure

The Brain Research Institute (BRI) uses various types of indirect measurements, including EEG and fMRI, to understand and assess brain activity and function. As well as the recovery of generic information about brain function, research also focuses on the utilisation of such data and understanding to study the initiation, dynamics, spread and suppression of epileptic seizures. To assist with the future focussing of this aspect of their research, the BRI asked the MISG 2010 participants to examine how the available EEG and fMRI data and current knowledge about epilepsy should be analysed and interpreted to yield an enhanced understanding about brain activity occurring before, at commencement of, during, and after a seizure. Though the deliberations of the study group were wide ranging in terms of the related matters considered and discussed, considerable progress was made with the following three aspects. (1) The science behind brain activity investigations depends crucially on the quality of the analysis and interpretation of, as well as the recovery of information from, EEG and fMRI measurements. A number of specific methodologies were discussed and formalised, including independent component analysis, principal component analysis, profile monitoring and change point analysis (hidden Markov modelling, time series analysis, discontinuity identification). (2) Even though EEG measurements accurately and very sensitively record the onset of an epileptic event or seizure, they are, from the perspective of understanding the internal initiation and localisation, of limited utility. They only record neuronal activity in the cortical (surface layer) neurons of the brain, which is a direct reflection of the type of electrical activity they have been designed to record. Because fMRI records, through the monitoring of blood flow activity, the location of localised brain activity within the brain, the possibility of combining fMRI measurements with EEG, as a joint inversion activity, was discussed and examined in detail. (3) A major goal for the BRI is to improve understanding about ``when'' (at what time) an epileptic seizure actually commenced before it is identified on an eeg recording, ``where'' the source of this initiation is located in the brain, and ``what'' is the initiator. Because of the general agreement in the literature that, in one way or another, epileptic events and seizures represent abnormal synchronisations of localised and/or global brain activity the modelling of synchronisations was examined in some detail. References C. M. Michel, G. Thut, S. Morand, A. Khateb, A. J. Pegna, R. Grave de Peralta, S. Gonzalez, M. Seeck and T. Landis, Electric source imaging of human brain functions, Brain Res. 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Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden

Over 80% of women diagnosed with advanced-stage ovarian cancer die as a result of disease recurrence due to failure of chemotherapy treatment. In this study, using two distinct ovarian cancer cell lines (epithelial OVCA 433 and mesenchymal HEY) we demonstrate enrichment in a population of cells with high expression of CSC markers at the protein and mRNA levels in response to cisplatin, paclitaxel and the combination of both. We also demonstrate a significant enhancement in the sphere forming abilities of ovarian cancer cells in response to chemotherapy drugs. The results of these in vitro findings are supported by in vivo mouse xenograft models in which intraperitoneal transplantation of cisplatin or paclitaxel-treated residual HEY cells generated significantly higher tumor burden compared to control untreated cells. Both the treated and untreated cells infiltrated the organs of the abdominal cavity. In addition, immunohistochemical studies on mouse tumors injected with cisplatin or paclitaxel treated residual cells displayed higher staining for the proliferative antigen Ki67, oncogeneic CA125, epithelial E-cadherin as well as cancer stem cell markers such as Oct4 and CD117, compared to mice injected with control untreated cells. These results suggest that a short-term single treatment of chemotherapy leaves residual cells that are enriched in CSC-like traits, resulting in an increased metastatic potential. The novel findings in this study are important in understanding the early molecular mechanisms by which chemoresistance and subsequent relapse may be triggered after the first line of chemotherapy treatment.

Epithelial-mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas : an exception to the norm

Cancer that arises from the ovarian surface epithelium (OSE) accounts for approximately 90% of human ovarian cancer, and is the fourth leading cause of cancer-related deaths among women in developed countries. The pathophysiology of epithelial ovarian cancer is still unclear because of the poor understanding of the complex nature of its development and the unusual mechanism(s) of disease progression. Recent studies have reported epithelial-mesenchymal transition (EMT) in cultured OSE and ovarian cancer cell lines in response to various stimuli, but our understanding of the importance of these observations for normal ovarian physiology and cancer progression is not well established. This review highlights the current literature on EMT-associated events in normal OSE and ovarian cancer cell lines, and discusses its implication for normal ovarian function as well as acquisition of neoplastic phenotypes. The pathological changes in OSE in response to EMT during neoplastic transformation and the contribution of hormones, growth factors, and cytokines that initiate and drive EMT to sustain normal ovarian function, as well as cancer development and progression are also discussed. Finally, emphasis is placed on the clinical implications of EMT and potential therapeutic opportunities that may arise from these observations have been proposed.

Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile

Epithelial mesenchymal transition (EMT) and cancer stem cells (CSC) have been associated with resistance to chemotherapy. Eighty percent of ovarian cancer patients initially respond to platinum-based combination therapy but most return with recurrence and ultimate demise. To better understand such chemoresistance we have assessed the potential role of EMT in tumor cells collected from advanced-stage ovarian cancer patients and the ovarian cancer cell line OVCA 433 in response to cisplatin in vitro. We demonstrate that cisplatin-induced transition from epithelial to mesenchymal morphology in residual cancer cells correlated with reduced E-cadherin, and increased N-cadherin and vimentin expression. The mRNA expression of Snail, Slug, Twist, and MMP-2 were significantly enhanced in response to cisplatin and correlated with increased migration. This coincided with increased cell surface expression of CSC-like markers such as CD44, α2 integrin subunit, CD117, CD133, EpCAM, and the expression of stem cell factors Nanog and Oct-4. EMT and CSC-like changes in response to cisplatin correlated with enhanced activation of extracellular signal-regulated kinase (ERK)1/2. The selective MEK inhibitor U0126 inhibited ERK2 activation and partially suppressed cisplatin-induced EMT and CSC markers. In vivo xenotransplantation of cisplatin-treated OVCA 433 cells in zebrafish embryos demonstrated significantly enhanced migration of cells compared to control untreated cells. U0126 inhibited cisplatin-induced migration of cells in vivo, suggesting that ERK2 signaling is critical to cisplatin-induced EMT and CSC phenotypes, and that targeting ERK2 in the presence of cisplatin may reduce the burden of residual tumor, the ultimate cause of recurrence in ovarian cancer patients.

Conceptualising, evaluating and reporting social resilience in vulnerable regional and remote communities facing climate change in tropical Queensland : marine and tropical sciences research facility transition project final report

Regional and remote communities in tropical Queensland are among Australia’s most vulnerable in the face of climate change. At the same time, these socially and economically vulnerable regions house some of Australia’s most significant biodiversity values. Past approaches to terrestrial biodiversity management have focused on tackling biophysical interventions through the use of biophysical knowledge. An equally important focus should be placed on building regional-scale community resilience if some of the worst biodiversity impacts of climate change are to be avoided or mitigated. Despite its critical need, more systemic or holistic approaches to natural resource management have been rarely trialed and tested in a structured way. Currently, most strategic interventions in improving regional community resilience are ad hoc, not theory-based and short term. Past planning approaches have not been durable, nor have they been well informed by clear indicators. Research into indicators for community resilience has been poorly integrated within adaptive planning and management cycles. This project has aimed to resolve this problem by: * Reviewing the community and social resilience and adaptive planning literature to reconceptualise an improved framework for applying community resilience concepts; * Harvesting and extending work undertaken in MTSRF Phase 1 to identifying the learnings emerging from past MTSRF research; * Distilling these findings to identify new theoretical and practical approaches to the application of community resilience in natural resource use and management; * Reconsidering the potential interplay between a region’s biophysical and social planning processes, with a focus on exploring spatial tools to communicate climate change risk and its consequent environmental, economic and social impacts, and; * Trialling new approaches to indicator development and adaptive planning to improve community resilience, using a sub-regional pilot in the Wet Tropics. In doing so, we also looked at ways to improve the use and application of relevant spatial information. Our theoretical review drew upon the community development, psychology and emergency management literature to better frame the concept of community resilience relative to aligned concepts of social resilience, vulnerability and adaptive capacity. Firstly, we consider community resilience as a concept that can be considered at a range of scales (e.g. regional, locality, communities of interest, etc.). We also consider that overall resilience at higher scales will be influenced by resilience levels at lesser scales (inclusive of the resilience of constituent institutions, families and individuals). We illustrate that, at any scale, resilience and vulnerability are not necessarily polar opposites, and that some understanding of vulnerability is important in determining resilience. We position social resilience (a concept focused on the social characteristics of communities and individuals) as an important attribute of community resilience, but one that needs to be considered alongside economic, natural resource, capacity-based and governance attributes. The findings from the review of theory and MTSRF Phase 1 projects were synthesized and refined by the wider project team. Five predominant themes were distilled from this literature, research review and an expert analysis. They include the findings that: 1. Indicators have most value within an integrated and adaptive planning context, requiring an active co-research relationship between community resilience planners, managers and researchers if real change is to be secured; 2. Indicators of community resilience form the basis for planning for social assets and the resilience of social assets is directly related the longer term resilience of natural assets. This encourages and indeed requires the explicit development and integration of social planning within a broader natural resource planning and management framework; 3. Past indicator research and application has not provided a broad picture of the key attributes of community resilience and there have been many attempts to elicit lists of “perfect” indicators that may never be useful within the time and resource limitations of real world regional planning and management. We consider that modeling resilience for proactive planning and prediction purposes requires the consideration of simple but integrated clusters of attributes; 4. Depending on time and resources available for planning and management, the combined use of well suited indicators and/or other lesser “lines of evidence” is more flexible than the pursuit of perfect indicators, and that; 5. Index-based, collaborative and participatory approaches need to be applied to the development, refinement and reporting of indicators over longer time frames. We trialed the practical application of these concepts via the establishment of a collaborative regional alliance of planners and managers involved in the development of climate change adaptation strategies across tropical Queensland (the Gulf, Wet Tropics, Cape York and Torres Strait sub-regions). A focus on the Wet Tropics as a pilot sub-region enabled other Far North Queensland sub-region’s to participate and explore the potential extension of this approach. The pilot activities included: * Further exploring ways to innovatively communicate the region’s likely climate change scenarios and possible environmental, economic and social impacts. We particularly looked at using spatial tools to overlay climate change risks to geographic communities and social vulnerabilities within those communities; * Developing a cohesive first pass of a State of the Region-style approach to reporting community resilience, inclusive of regional economic viability, community vitality, capacitybased and governance attributes. This framework integrated a literature review, expert (academic and community) and alliance-based contributions; and * Early consideration of critical strategies that need to be included in unfolding regional planning activities with Far North Queensland. The pilot assessment finds that rural, indigenous and some urban populations in the Wet Tropics are highly vulnerable and sensitive to climate change and may require substantial support to adapt and become more resilient. This assessment finds that under current conditions (i.e. if significant adaptation actions are not taken) the Wet Tropics as a whole may be seriously impacted by the most significant features of climate change and extreme climatic events. Without early and substantive action, this could result in declining social and economic wellbeing and natural resource health. Of the four attributes we consider important to understanding community resilience, the Wet Tropics region is particularly vulnerable in two areas; specifically its economic vitality and knowledge, aspirations and capacity. The third and fourth attributes, community vitality and institutional governance are relatively resilient but are vulnerable in some key respects. In regard to all four of these attributes, however, there is some emerging capacity to manage the possible shocks that may be associated with the impacts of climate change and extreme climatic events. This capacity needs to be carefully fostered and further developed to achieve broader community resilience outcomes. There is an immediate need to build individual, household, community and sectoral resilience across all four attribute groups to enable populations and communities in the Wet Tropics region to adapt in the face of climate change. Preliminary strategies of importance to improve regional community resilience have been identified. These emerging strategies also have been integrated into the emerging Regional Development Australia Roadmap, and this will ensure that effective implementation will be progressed and coordinated. They will also inform emerging strategy development to secure implementation of the FNQ 2031 Regional Plan. Of most significance in our view, this project has taken a co-research approach from the outset with explicit and direct importance and influence within the region’s formal planning and management arrangements. As such, the research: * Now forms the foundations of the first attempt at “Social Asset” planning within the Wet Tropics Regional NRM Plan review; * Is assisting Local government at regional scale to consider aspects of climate change adaptation in emerging planning scheme/community planning processes; * Has partnered the State government (via the Department of Infrastructure and Planning and Regional Managers Coordination Network Chair) in progressing the Climate Change adaptation agenda set down within the FNQ 2031 Regional Plan; * Is informing new approaches to report on community resilience within the GBRMPA Outlook reporting framework; and * Now forms the foundation for the region’s wider climate change adaptation priorities in the Regional Roadmap developed by Regional Development Australia. Through the auspices of Regional Development Australia, the outcomes of the research will now inform emerging negotiations concerning a wider package of climate change adaptation priorities with State and Federal governments. Next stage research priorities are also being developed to enable an ongoing alliance between researchers and the region’s climate change response.

Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden

Background Current treatment of ovarian cancer patients with chemotherapy leaves behind a residual tumor which results in recurrent ovarian cancer within a short time frame. We have previously demonstrated that a single short-term treatment of ovarian cancer cells with chemotherapy in vitro resulted in a cancer stem cell (CSC)-like enriched residual population which generated significantly greater tumor burden compared to the tumor burden generated by control untreated cells. In this report we looked at the mechanisms of the enrichment of CSC-like residual cells in response to paclitaxel treatment. Methods The mechanism of survival of paclitaxel-treated residual cells at a growth inhibitory concentration of 50% (GI50) was determined on isolated tumor cells from the ascites of recurrent ovarian cancer patients and HEY ovarian cancer cell line by in vitro assays and in a mouse xenograft model. Results Treatment of isolated tumor cells from the ascites of ovarian cancer patients and HEY ovarian cancer cell line with paclitaxel resulted in a CSC-like residual population which coincided with the activation of Janus activated kinase 2 (JAK2) and signal transducer and activation of transcription 3 (STAT3) pathway in paclitaxel surviving cells. Both paclitaxel-induced JAK2/STAT3 activation and CSC-like characteristics were inhibited by a low dose JAK2-specific small molecule inhibitor CYT387 (1 μM) in vitro. Subsequent, in vivo transplantation of paclitaxel and CYT387-treated HEY cells in mice resulted in a significantly reduced tumor burden compared to that seen with paclitaxel only-treated transplanted cells. In vitro analysis of tumor xenografts at protein and mRNA levels demonstrated a loss of CSC-like markers and CA125 expression in paclitaxel and CYT387-treated cell-derived xenografts, compared to paclitaxel only-treated cell-derived xenografts. These results were consistent with significantly reduced activation of JAK2 and STAT3 in paclitaxel and CYT387-treated cell-derived xenografts compared to paclitaxel only-treated cell derived xenografts. Conclusions This proof of principle study demonstrates that inhibition of the JAK2/STAT3 pathway by the addition of CYT387 suppresses the ‘stemness’ profile in chemotherapy-treated residual cells in vitro, which is replicated in vivo, leading to a reduced tumor burden. These findings have important implications for ovarian cancer patients who are treated with taxane and/or platinum-based therapies. Keywords: Ovarian carcinoma, Cancer stem cell, Metastasis, Ascites, Chemoresistance, Recurrence, JAK2/STAT3 pathway

Transforming the future of treatment for ovarian cancer

As for many other cancers, metastasis is the leading cause of death of patients with ovarian cancer. Vigorous basic and clinical research is being performed to initiate more efficacious treatment strategies to improve the poor outcome of women with this cancer. Current treatment for ovarian cancer includes advanced cyto-reductive surgery and traditional platinum and taxane combined chemotherapy. Clinical trials using novel cytotoxic reagents and tyrosine kinase inhibitors have also been progressing. In parallel, the application of robust unbiased high throughput research platforms using transcriptomic and proteomic approaches has identified that not only individual cell signalling pathways, but a network of molecular pathways, play an important role in the biology of ovarian cancer. Furthermore, intensive genomic and epigenetic analyses have also revealed single nucleotide polymorphisms associated with risk and/or aetiology of this cancer including patient response to treatment. Taken together, these approaches, that are advancing our understanding, will have an impact on the generation of new therapeutic approaches and strategies for improving the outcome and quality of life of patients with ovarian cancer in the near future.

Dopamine transporter genotype predicts behavioural and neural measures of response inhibition

The ability to inhibit unwanted actions is a heritable executive function that may confer risk to disorders such as attention deficit hyperactivity disorder (ADHD). Converging evidence from pharmacology and cognitive neuroscience suggests that response inhibition is instantiated within frontostriatal circuits of the brain with patterns of activity that are modulated by the catecholamines dopamine and noradrenaline. A total of 405 healthy adult participants performed the stop-signal task, a paradigmatic measure of response inhibition that yields an index of the latency of inhibition, termed the stop-signal reaction time (SSRT). Using this phenotype, we tested for genetic association, performing high-density single-nucleotide polymorphism mapping across the full range of autosomal catecholamine genes. Fifty participants also underwent functional magnetic resonance imaging to establish the impact of associated alleles on brain and behaviour. Allelic variation in polymorphisms of the dopamine transporter gene (SLC6A3: rs37020; rs460000) predicted individual differences in SSRT, after corrections for multiple comparisons. Furthermore, activity in frontal regions (anterior frontal, superior frontal and superior medial gyri) and caudate varied additively with the T-allele of rs37020. The influence of genetic variation in SLC6A3 on the development of frontostriatal inhibition networks may represent a key risk mechanism for disorders of behavioural inhibition.

Engineered microenvironments provide new insights into ovarian and prostate cancer progression and drug responses

Tissue engineering technologies, which have originally been designed to reconstitute damaged tissue structure and function, can mimic not only tissue regeneration processes but also cancer development and progression. Bioengineered approaches allow cell biologists to develop sophisticated experimentally and physiologically relevant cancer models to recapitulate the complexity of the disease seen in patients. Tissue engineering tools enable three-dimensionality based on the design of biomaterials and scaffolds that re-create the geometry, chemistry, function and signalling milieu of the native tumour microenvironment. Three-dimensional (3D) microenvironments, including cell-derived matrices, biomaterial-based cell culture models and integrated co-cultures with engineered stromal components, are powerful tools to study dynamic processes like proteolytic functions associated with cancer progression, metastasis and resistance to therapeutics. In this review, we discuss how biomimetic strategies can reproduce a humanised niche for human cancer cells, such as peritoneal or bone-like microenvironments, addressing specific aspects of ovarian and prostate cancer progression and therapy response.

A biomarker panel to discriminate between systemic inflammatory response syndrome and sepsis and sepsis severity

Introduction: In this study, we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) versus sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients who survived sepsis from those who did not. Materials and Methods: Our study group consisted of 16 patients, of which 6 died and 10 survived. We daily measured 28 plasma proteins, for the whole stay of the patients in the ICU. Results: We observed that metalloproteinases and sE-selectin play a role in the distinction between SIRS and sepsis, and that IL-1, IP-10, sTNF-R2 and sFas appear to be indicative for the progression from sepsis to septic shock. A combined measurement of MMP-3, -10, IL-1, IP-10, sIL-2R, sFas, sTNF-R1, sRAGE, GM-CSF, IL-1 and Eotaxin allows for a good separation of patients that survived from those that died (mortality prediction with a sensitivity of 79% and specificity of 86%). Correlation analysis suggests a novel interaction between IL-1a and IP-10. Conclusion: The marker panel is ready to be verified in a validation study with or without therapeutic intervention.