It’s okay to ask : development and pilot testing of a question prompt list for patients with brain tumours

Background: Previous research identified that primary brain tumour patients have significant psychological morbidity and unmet needs, particularly the need for more information and support. However, the utility of strategies to improve information provision in this setting is unknown. This study involved the development and piloting of a brain tumour specific question prompt list (QPL). A QPL is a list of questions patients may find useful to ask their health professionals, and is designed to facilitate communication and information exchange. Methods: Thematic analysis of QPLs developed for other chronic diseases and brain tumour specific patient resources informed a draft QPL. Subsequent refinement of the QPL involved an iterative process of interviews and review with 12 recently diagnosed patients and six caregivers. Final revisions were made following readability analyses and review by health professionals. Piloting of the QPL is underway using a non-randomised control group trial with patients undergoing treatment for a primary brain tumour in Brisbane, Queensland. Following baseline interviews, consenting participants are provided with the QPL or standard information materials. Follow-up interviews four to 6 weeks later allow assessment of the acceptability of the QPL, how it is used by patients, impact on information needs, and feasibility of recruitment, implementation and outcome assessment. Results: The final QPL was determined to be readable at the sixth grade level. It contains seven sections: diagnosis, prognosis, symptoms and changes, the health professional team, support, treatment and management, and post-treatment concerns. At this time, fourteen participants have been recruited for the pilot, and data collection completed for eleven. Data collection and preliminary analysis are expected to be completed by and presented at the conference. Conclusions: If acceptable to participants, the QPL may encourage patients, doctors and nurses to communicate more effectively, reducing unmet information needs and ultimately improving psychological wellbeing.

Alternative primary sources for studying Australian television history : an annotated list of online private collections

It is possible to write many different histories of Australian television, and these different histories draw on different primary sources. The ABC of Drama, for example, draws on the ABC Document Archives (Jacka 1991). Most of the information for Images and Industry: television drama production in Australia is taken from original interviews with television production staff (Moran 1985). Ending the Affair, as well as archival work, draws on ‘over ten years of watching … Australian television current affairs’ (Turner 2005, xiii). Moran’s Guide to Australian TV Series draws exhaustively on extant archives: the ABC Document Archives, material sourced through the ABC Drama department, the Australian Film Commission, the library of the Australian Film, Television and Radio School, and the Australian Film Institute (Moran 1993, xi)...

VAMP3 regulates podosome organisation in macrophages and together with Stx4/SNAP23 mediates adhesion, cell spreading and persistent migration

The ability of cells to adhere, spread and migrate is essential to many physiological processes, particularly in the immune system where cells must traffic to sites of inflammation and injury. By altering the levels of individual components of the VAMP3/Stx4/SNAP23 complex we show here that this SNARE complex regulates efficient macrophage adhesion, spreading and migration on fibronectin. During cell spreading this complex mediates the polarised exocytosis of VAMP3- positive recycling endosome membrane into areas of membrane expansion, where VAMP3's surface partner Q-SNARE complex Stx4/SNAP23 was found to accumulate. Lowering the levels of VAMP3 in spreading cells resulted in a more rounded cell morphology and most cells were found to be devoid of the typical ring-like podosome superstructures seen normally in spreading cells. In migrating cells lowering VAMP3 levels disrupted the polarised localisation of podosome clusters. The reduced trafficking of recycling endosome membrane to sites of cell spreading and the disorganised podosome localisation in migrating macrophages greatly reduced their ability to persistently migrate on fibronectin. Thus, this important SNARE complex facilitates macrophage adhesion, spreading, and persistent macrophage migration on fibronectin through the delivery of VAMP3-positive membrane with its cargo to expand the plasma membrane and to participate in organising adhesive podosome structures.

Models of collective cell behaviour with crowding effects : comparing lattice-based and lattice-free approaches

Individual-based models describing the migration and proliferation of a population of cells frequently restrict the cells to a predefined lattice. An implicit assumption of this type of lattice based model is that a proliferative population will always eventually fill the lattice. Here we develop a new lattice-free individual-based model that incorporates cell-to-cell crowding effects. We also derive approximate mean-field descriptions for the lattice-free model in two special cases motivated by commonly used experimental setups. Lattice-free simulation results are compared to these mean-field descriptions and to a corresponding lattice-based model. Data from a proliferation experiment is used to estimate the parameters for the new model, including the cell proliferation rate, showing that the model fits the data well. An important aspect of the lattice-free model is that the confluent cell density is not predefined, as with lattice-based models, but an emergent model property. As a consequence of the more realistic, irregular configuration of cells in the lattice-free model, the population growth rate is much slower at high cell densities and the population cannot reach the same confluent density as an equivalent lattice-based model.

A biphasic scaffold design combined with cell sheet technology for simultaneous regeneration of alveolar bone/periodontal ligament complex

This study describes the design of a biphasic scaffold composed of a Fused Deposition Modeling scaffold (bone compartment) and an electrospun membrane (periodontal compartment) for periodontal regeneration. In order to achieve simultaneous alveolar bone and periodontal ligament regeneration a cell-based strategy was carried out by combining osteoblast culture in the bone compartment and placement of multiple periodontal ligament (PDL) cell sheets on the electrospun membrane. In vitro data showed that the osteoblasts formed mineralized matrix in the bone compartment after 21 days in culture and that the PDL cell sheet harvesting did not induce significant cell death. The cell-seeded biphasic scaffolds were placed onto a dentin block and implanted for 8 weeks in an athymic rat subcutaneous model. The scaffolds were analyzed by μCT, immunohistochemistry and histology. In the bone compartment, a more intense ALP staining was obtained following seeding with osteoblasts, confirming the μCT results which showed higher mineralization density for these scaffolds. A thin mineralized cementum-like tissue was deposited on the dentin surface for the scaffolds incorporating the multiple PDL cell sheets, as observed by H&E and Azan staining. These scaffolds also demonstrated better attachment onto the dentin surface compared to no attachment when no cell sheets were used. In addition, immunohistochemistry revealed the presence of CEMP1 protein at the interface with the dentine. These results demonstrated that the combination of multiple PDL cell sheets and a biphasic scaffold allows the simultaneous delivery of the cells necessary for in vivo regeneration of alveolar bone, periodontal ligament and cementum. © 2012 Elsevier Ltd.

Effect Of changes in sodium intake on cell transport parameters

Changing sodium intake from 70-200 mmol/day elevates blood pressure in normotensive volunteers by 6/4 mmHg. Older people, people with reduced renal function on a low sodium diet and people with a family history of hypertension are more likely to show this effect. The rise in blood pressure was associated with a fall in plasma volume suggesting that plasma volume changes do not initiate hypertension. In normotensive individuals the most common abnormality in membrane sodium transport induced by an extra sodium load was an increased permeability of the red cell to sodium. Some normotensive individuals also had an increase in the level of a plasma inhibitor that inhibited Na-K ATPase. These individuals also appeared to have a rise in blood pressure. Sodium intake and blood pressure are related. The relationship differs in different people and is probably controlled by the genetically inherited capacity of systems involved in membrane sodium transport.

Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

PARP inhibition induces BAX/BAK-independent synthetic lethality of BRCA1-deficient non-small cell lung cancer

Evasion of apoptosis contributes to both tumourigenesis and drug resistance in non-small cell lung carcinoma (NSCLC). The pro-apoptotic BCL-2 family proteins BAX and BAK are critical regulators of mitochondrial apoptosis. New strategies for targeting NSCLC in a mitochondria-independent manner should bypass this common mechanism of apoptosis block. BRCA1 mutation frequency in lung cancer is low; however, decreased BRCA1 mRNA and protein expression levels have been reported in a significant proportion of lung adenocarcinomas. BRCA1 mutation/deficiency confers a defect in homologous recombination DNA repair that has been exploited by synthetic lethality through inhibition of PARP (PARPi) in breast and ovarian cells; however, it is not known whether this same synthetic lethal mechanism exists in NSCLC cells. Additionally, it is unknown whether the mitochondrial apoptotic pathway is required for BRCA1/PARPi-mediated synthetic lethality. Here we demonstrate that silencing of BRCA1 expression by RNA interference sensitizes NSCLC cells to PARP inhibition. Importantly, this sensitivity was not attenuated in cells harbouring mitochondrial apoptosis block induced by co-depletion of BAX and BAK. Furthermore, we demonstrate that BRCA1 inhibition cannot override platinum resistance, which is often mediated by loss of mitochondrial apoptosis signalling, but can still sensitize to PARP inhibition. Finally we demonstrate the existence of a BRCA1-deficient subgroup (11–19%) of NSCLC patients by analysing BRCA1 protein levels using immunohistochemistry in two independent primary NSCLC cohorts. Taken together, the existence of BRCA1-immunodeficient NSCLC suggests that this molecular subgroup could be effectively targeted by PARP inhibitors in the clinic and that PARP inhibitors could be used for the treatment of BRCA1-immunodeficient, platinum-resistant tumours.