A physiologically relevant 3D collagen-based scaffold-neuroblastoma cell system exhibits chemosensitivity similar to orthotopic xenograft models.

3D scaffold-based in vitro cell culturing is a recent technological advancement in cancer research bridging the gap between conventional 2D culture and in vivo tumours. The main challenge in treating neuroblastoma, a paediatric cancer of the sympathetic nervous system, is to combat tumour metastasis and resistance to multiple chemotherapeutic drugs. The aim of this study was to establish a physiologically relevant 3D neuroblastoma tissue-engineered system and explore its therapeutic relevance. Two neuroblastoma cell lines, chemotherapeutic sensitive Kelly and chemotherapeutic resistant KellyCis83 were cultured in a 3D in vitro model on two collagen-based scaffolds containing either glycosaminoglycan (Coll-GAG) or nanohydroxyapatite (Coll-nHA) and compared to 2D cell culture and an orthotopic murine model. Both neuroblastoma cell lines actively infiltrated the scaffolds and proliferated displaying >100-fold increased resistance to cisplatin treatment when compared to 2D cultures, exhibiting chemosensitivity similar to orthotopic xenograft in vivo models. This model demonstrated its applicability to validate miRNA-based gene delivery. The efficacy of liposomes bearing miRNA mimics uptake and gene knockdown was similar in both 2D and 3D in vitro culturing models highlighting the proof-of-principle for the applicability of 3D collagen-based scaffolds cell system for validation of miRNA function. Collectively, this data shows the successful development and characterisation of a physiologically relevant, scaffold-based 3D tissue-engineered neuroblastoma cell model, strongly supporting its value in the evaluation of chemotherapeutics, targeted therapies and investigation of neuroblastoma pathogenesis. While neuroblastoma is the specific disease being focused upon, the platform may have multi-functionality beyond this tumour type. STATEMENT OF SIGNIFICANCE: Traditional 2D cell cultures do not completely capture the 3D architecture of cells and extracellular matrix contributing to a gap in our understanding of mammalian biology at the tissue level and may explain some of the discrepancies between in vitro and in vivo results. Here, we demonstrated the successful development and characterisation of a physiologically relevant, scaffold-based 3D tissue-engineered neuroblastoma cell model, strongly supporting its value in the evaluation of chemotherapeutics, targeted therapies and investigation of neuroblastoma pathogenesis. The ability to test drugs in this reproducible and controllable tissue-engineered model system will help reduce the attrition rate of the drug development process and lead to more effective and tailored therapies. Importantly, such 3D cell models help to reduce and replace animals for pre-clinical research addressing the principles of the 3Rs.

Factors affecting jump performance in professional Australian rules footballers.

AIM: This study examined factors contributing to jump performance in professional Australian Rules Football (ARF) players. METHODS: Thirty-two ARF players performed a countermovement jump (CMJ) and were divided into groups based on jump performance: high calibre (HC) or low calibre (LC). During CMJ assessment, force, rate of force development, movement velocity and power were measured. Physical measures included mass, height, age, lower body strength, eccentric utilization ratio and leg stiffness (Kleg). HC and LC groups were compared to determine the variables contributing to jump performance and correlation and regression analyses also aided in identifying such variables. CMJ height was higher in the HC group (P<0.001). RESULTS: The HC group demonstrated a higher CMJ velocity (9.8%, P=0.004) and CMJ power (14.4%, P=0.042) when compared to the LC group. Further, the HC group demonstrated 7.5% higher Kleg than the LC group (P=0.019). Spearman's rho correlations demonstrated moderate-large relationships between jump height and strength, velocity and power, while the regression analysis revealed velocity was the sole predictive variable of jump performance. Jumping performance clearly differs within a group of professional ARF athletes. CONCLUSION: Movement velocity appears to be an important factor contributing to jump performance; however, lower body power and Kleg are also important for jump performance.

HeartBeat--improving heart attack care.

We aimed to save lives by assuring best practice in ST elevation myocardial infarction (STEMI) through initiating the Institute for Healthcare Improvement (IHI) methodology nationally. Following collection of a minimum dataset, annual change in indicators in the five initiating hospitals for the period Oct 2006 - Sept 2009 was assessed by analysing the percentage of patients receiving the eight components of evidenced based care on admission and discharge and in-hospital mortality rate. For 635 patients, performance on seven of the eight indicators of care exceeded 90% annually. Timely reperfusion therapy (thrombolysis, primary percutaneous coronary intervention (PPCI)) improved non-significantly from 68.2% (107 patients) in year 1 to 77.1% (118 patients) in year 3. In-hospital mortality declined significantly from 12.4% (24 deaths) in year 1 to 5% (9 deaths) in year 3. Evidence based STEMI care is followed to a high degree but timely reperfusion and PPCI provision remain a challenge nationally.

A gamma-ray burst at a redshift of z approximately 8.2.

Long-duration gamma-ray bursts (GRBs) are thought to result from the explosions of certain massive stars, and some are bright enough that they should be observable out to redshifts of z > 20 using current technology. Hitherto, the highest redshift measured for any object was z = 6.96, for a Lyman-alpha emitting galaxy. Here we report that GRB 090423 lies at a redshift of z approximately 8.2, implying that massive stars were being produced and dying as GRBs approximately 630 Myr after the Big Bang. The burst also pinpoints the location of its host galaxy.

Forgiveness. A concept analysis.

This article provides an operational definition of forgiveness as a first step in the systematic analysis of the concept. Using the method described by Walker and Avant (1995), the authors identify the attributes and characteristics of forgiveness and its theoretical and practical implications for nursing. Sample cases from clinical practice help illustrate the concept further. Further nursing research needs to test the theoretical relationships between forgiveness and nursing practice outcomes.