Novel mTORC1 Inhibitors Kill Glioblastoma Stem Cells.

Glioblastoma (GBM) is an aggressive tumor of the brain, with an average post-diagnosis survival of 15 months. GBM stem cells (GBMSC) resist the standard-of-care therapy, temozolomide, and are considered a major contributor to tumor resistance. Mammalian target of rapamycin Complex 1 (mTORC1) regulates cell proliferation and has been shown by others to have reduced activity in GBMSC.

Cetylpyridinium chloride is a potent AMP-activated kinase (AMPK) inducer and has therapeutic potential in cancer.

AMP-activated protein kinase (AMPK) is a eukaryotic energy sensor and protector from mitochondrial/energetic stress that is also a therapeutic target for cancer and metabolic disease. Metformin is an AMPK inducer that has been used in cancer therapeutic trials. Through screening we isolated cetylpyridinium chloride (CPC), a drug known to dose-dependently inhibit mitochondrial complex 1, as a potent and dose-dependent AMPK stimulator.

Idebenone is a cytoprotective insulin sensitizer whose mechanism is Shc inhibition.

When insulin binds insulin receptor, IRS1 signaling is stimulated to trigger the maximal insulin response. p52Shc protein competes directly with IRS1, thus damping and diverting maximal insulin response. Genetic reduction of p52Shc minimizes competition with IRS1, and improves insulin signaling and glucose control in mice, and improves pathophysiological consequences of hyperglycemia.

Small molecules bind human mTOR protein and inhibit mTORC1 specifically.

Inhibition of mTOR activity (mechanistic target of rapamycin) is an anti-cancer therapeutic strategy. mTOR participates in two functional complexes, mTORC1 and mTORC2. Since mTORC1 is specifically activated in multiple tumors, novel molecules that inhibit mTORC1 could be therapeutically important.

Nurses' experiences assessing the spirituality of terminally ill patients in acute clinical practice.

Aim: To explore and describe how nurses define spirituality and incorporate spiritual care into their clinical practice.

Method: A two-phase, mixed-methods, explanatory descriptive design was adopted. Sixteen nurses working in an acute medical ward completed a purpose-designed questionnaire.

Detection of rapidly growing mycobacteria in routine cultures of samples from patients with cystic fibrosis.

Rapidly growing mycobacteria (RGM) are respiratory pathogens in patients with cystic fibrosis (CF), but detection generally requires specialized cultures for acid-fast bacilli (AFB; AFB cultures). We determined that RGM could be recovered from routine cultures of samples from patients with CF by extending incubation of the Burkholderia cepacia selective agar (BCSA) from 5 to 14 days. To explore the impact of this modification, we compared results from routine and AFB cultures of samples from CF patients for 2 years before (4,212 samples by routine culture, 1,810 samples by AFB culture, 670 patients) and 2 years after (4,720 samples by routine culture, 2,179 samples by AFB culture, 695 patients) the change.

Gaining human ethics approval: a strategy for refining research studies.

We argue that developing a human ethics application is an effective method for refining the intent and design of research studies. Our study aimed to investigate the delivery of end-of-life and palliative care nursing to residents of an aged care unit in a Multi-purpose Service/Centre in rural Victoria. We used the ethics application process as a strategy to focus the study, and to refine the data collection and analysis techniques.

The evolution of palliative care and the relevance to residential aged care: understanding the past to inform the future.

Improving the experience of dying in residential aged care units became a significant project of the Australian Government's National Palliative Care Program in 2004. This initiative resulted in an expectation that residential aged care facilities would adopt the recommended palliative approach to underpin service delivery. Recognising palliative care as a specialist area of health care practice is a recent development which has influenced the expectations of community and government.

Examining the methods used for a critical ethnographic enquiry.

Methodology articulates the broad theoretical and philosophical framework which researchers employ when conducting an inquiry. Methods are the procedural rules by which research inquiry is conducted; giving authority to articulate and communicate information as reliable and accurate in nature. Critical ethnography delves beneath the surface to examine the power relations and influences affecting phenomena by using field methods to identify not only culture, the 'consciousness' or the 'lived experiences' of others, but also exposing the political, social and material disempowerment of individuals and disadvantaged groups in order to elicit change.

The implications of policy on delivering a palliative approach in residential aged care: rhetoric or reality?

This critical ethnographic study aimed to understand policy and documentation in relationship to guiding nursing practice in delivering a palliative approach to residents of an aged care unit of a Multi-purpose Service (MPS). A thematic analysis was undertaken that searched the text for cultural determinants of practice, and similarities and differences between the data sets. Where discrepancies occurred, key informants were revisited and questioned regarding anomalies.

The importance of language for nursing: does it convey commonality of meaning and is it important to do so.

Objective: Language is the medium by which communication is both conveyed and received. To understand and communicate meaning it is necessary to examine the theoretical basis of word conceptualisation. The determinants of understanding language however are somewhat elusive and idiosyncratic by nature.

Research an exciting journey and a career statement: a means to an end, putting rurality on the nursing research agenda.

Two issues were of importance to nurses in rural areas considering postgraduate studies. The first was the need for part-time study and what this entails. The second was a request that there be no research component within the postgraduate courses they identified.

Prevalence of vancomycin-resistant enterococcus in prenatal screening cultures.

Recommendations for the perinatal treatment of women colonized with Streptococcus agalactiae include vancomycin prophylaxis for those with severe penicillin allergies and antibiotic-resistant organisms. Because of potential postpartum infections due to vancomycin-resistant enterococci (VRE) and the possible spread of vancomycin resistance, the prevalence of VRE in prenatal screening cultures was determined.