A multicenter randomized controlled trial comparing three-times-a-day intermittent enteral postural feeding to continuous enteral feeding among mechanically ventilated patients in intensive care.

Background And Aims: Previous randomized controlled trials (RCTs) comparing intermittent feeding versus continuous feeding used different methods, employed shorter fasting intervals, ignored patients' posture in bed during feeds, and showed mixed results. Prolonged fasting intervals are hypothesized to have several benefits. Additionally, there is evidence for more efficient gastric emptying in the right lateral position.

The Future of Disability Research in Australia: Protocol for a Multiphase Research Agenda-Setting Study.

Background: For people with disabilities to live a good life, it is essential that funded research in health and social care addresses their interests, meets their needs, and fills gaps in our understanding of the impact that services, systems, and policies may have on them. Decisions about research funding should be based on an understanding of the research priorities of people with disabilities, their supporters and allies, disability researchers, service providers, and policy makers working in the field.

Objective: The aim of this protocol is to describe the research design and methods of a large-scale, disability research agenda-setting exercise conducted in 2021 in Australia.

Transcending the Professional-Client Divide: Supporting Young People with Complex Support Needs Through Transitions.

Young people with complex support needs frequently experience multiple intersecting forms of disadvantage including experiences of violence, abuse and neglect, housing instability and homelessness, problematic substance use, exclusion from education, and contact with the criminal justice system. Many of these young people have mental health, cognitive disability and/or other health issues that also impact on their lives. These young people need to navigate multiple, diverse, and often difficult transitions between services, adding to the existing chaos in their lives.

Intensive care unit outcomes in patients with hematological malignancy.

Unlabelled: Hematological malignancies are usually life-limiting conditions. Limitations of care need to be decided early, based on acceptability to the patient, family, physician, and community. Inappropriate intensive care unit (ICU) admission is likely to result in significant physical, psychological, and economic burden.

Choosing the harder road: Naming the challenges for families in person-centred planning.

Person-centred planning (PCP) has underpinned disability service provision in many Western countries for the past 30 years. For many people with an intellectual disability, family members are central to this process and are important allies in facilitating positive change. This article presents findings from an evaluation of a family resourcing and capacity building project in New South Wales (NSW), Australia.

Crafting and retelling everyday lives--disabled people's contribution to bioethical concerns.

This commentary draws out themes from the narrative symposium on "living with the label "disability"" from the perspective of auto/biography and critical disability studies in the humanities. It notes the disconnect between the experiences discussed in the stories and the preoccupations of bioethicists. Referencing Rosemarie Garland-Thompson's recent work, it suggests that life stories by people usually described as "disabled" offer narrative, epistemic and ethical resources for bioethics.

Increased activity of cell surface peptidases in HeLa cells undergoing UV-induced apoptosis is not mediated by caspase 3.

We have previously shown that in HeLa cells treated with a variety of agents there is an increase in cell surface peptidase (CSP) activity in those cells undergoing apoptosis. The increase in CSP activity observed in UVB-irradiated cells undergoing apoptosis was unaffected when the cultures were treated with the aminopeptidase inhibitor bestatin, and matrix metalloprotease inhibitor BB3103, but greatly enhanced when treated with the caspase 3 inhibitor-DEVD, and reduced in the presence of the poly(ADP-ribose) polymerase (PARP) inhibitor-3-aminobenzamide (3AB). Neither 3AB nor DEVD had an effect on the gross morphology of the apoptotic cells observed under electron microscopy, nor did they have an effect on phosphatidylserine eversion on the cell membrane, or that of PARP cleavage.

Dendritic cell immunotherapy for stage IV melanoma.

Active boosting of the antitumour immune response of patients with solid malignancies has been tested in a large number of trials. Isolated complete clinical responses have been reported, however, they have not been replicated in subsequent studies. We recently reported objective clinical responses to a dendritic cell/irradiated autologous tumour cell 'vaccine' in patients with distant metastatic (stage IV) melanoma.

Facultative or obligate anaerobic bacteria have the potential for multimodality therapy of solid tumours.

Recent understanding of the unique pathology of solid tumours has shed light on the difficult and disappointing nature of their clinical treatment. All solid tumours undergo angiogenesis that results in biological changes and adaptive metabolisms, i.e.

The development and characterization of an HEK293-derived cell line for use in an intratumoral cytokine delivery system.

As part of ongoing work to develop a method of cytokine delivery for use as an intratumoral depot, we noted that HEK293 cells, encapsulated in alginate, died within 24-48 h after in vivo, intratumoral implantation. We hypothesized that the highly hypoxic and acidic conditions found inside the tumor was the cause of the cells' premature demise. Therefore, we set out to develop a cell line, derived from HEK293, that would survive these hostile conditions.

An extraordinarily high level of IL-15 expression by a cell line transduced with a modified BMGneo vector displays hypoxic upregulation.

Interleukin (IL)-15 expression level is tightly controlled in mammalian cells by various mechanisms. In order to achieve higher expression levels of IL-15, many attempts have been made, but the highest expression rate among those reported is still only 13.3 ng/106 cells/24 h.

Immunological characteristics correlating with clinical response to immunotherapy in patients with advanced metastatic melanoma.

Current treatment options for advanced metastatic melanoma are limited to experimental regimen that provide poor survival outcomes. Immunotherapy is a promising alternative and we recently reported a clinical trial in which 6 out of 19 patients enrolled had objective clinical responses to a fully autologous melanoma/dendritic cell vaccine. The mechanism of the vaccine is not well understood, but we hypothesized that general immunocompetence may be a determinant of clinical response.

The Development and Characterization of an HEK293-Derived Cell Line for Use in an Intratumoral Cytokine Delivery System.

As part of ongoing work to develop a method of cytokine delivery for use as an intratumoral depot, we noted that HEK293 cells, encapsulated in alginate, died within 24-48 h after in vivo, intratumoral implantation. We hypothesized that the highly hypoxic and acidic conditions found inside the tumor was the cause of the cells' premature demise. Therefore, we set out to develop a cell line, derived from HEK293, that would survive these hostile conditions.

Search for "weapons of mass destruction" for cancer -- immuno/ gene therapy comes of age.

The complexity of a cancer, such as cell heterogeneity, and the existence of hypoxia, stromal cells and stem cells has so far prevented successful development and treatment of patients suffering from the later stages of cancers. At present, the use of conventional therapies, such as chemo/radio therapy is limited, and only therapies that are focused on utilizing the patient's immune response to combat against the disease appear to be the most reliable and promising. Two decades ago, cytokines were discovered to be able to activate the immune systems and mount an anti-tumour response.

Gene transfer to dendritic cells induced a protective immunity against melanoma.

Lentiviral vectors have shown promises for efficient gene transfer to dividing as well as nondividing cells. In this study, we explored lentiviral vector-mediated, the entire mTRP-2 gene transfer and expression in dendritic cells (DCs). Adoptive transfer of DCs-expressing mTRP-2 (DC-HR'CmT2) into C57BL/6 mouse was also assessed.

The significance of controlled conditions in lentiviral vector titration and in the use of multiplicity of infection (MOI) for predicting gene transfer events.

BACKGROUND: Although lentiviral vectors have been widely used for in vitro and in vivo gene therapy researches, there have been few studies systematically examining various conditions that may affect the determination of the number of viable vector particles in a vector preparation and the use of Multiplicity of Infection (MOI) as a parameter for the prediction of gene transfer events. METHODS: Lentiviral vectors encoding a marker gene were packaged and supernatants concentrated. The number of viable vector particles was determined by in vitro transduction and fluorescent microscopy and FACs analyses.

Microarray expression profiling in melanoma reveals a BRAF mutation signature.

We have used microarray gene expression profiling and machine learning to predict the presence of BRAF mutations in a panel of 61 melanoma cell lines. The BRAF gene was found to be mutated in 42 samples (69%) and intragenic mutations of the NRAS gene were detected in seven samples (11%). No cell line carried mutations of both genes.

Durable complete clinical responses in a phase I/II trial using an autologous melanoma cell/dendritic cell vaccine.

Advanced metastatic melanoma is incurable by standard treatments, but occasionally responds to immunotherapy. Recent trials using dendritic cells (DC) as a cellular adjuvant have concentrated on defined peptides as the source of antigens, and rely on foreign proteins as a source of help to generate a cell-mediated immune response. This approach limits patient accrual, because currently defined, non-mutated epitopes are restricted by a small number of human leucocyte antigens.

Treatment of non-resectable hepatocellular carcinoma with autologous tumor-pulsed dendritic cells.

Background: The response of hepatocellular carcinoma (HCC) to therapy is often disappointing and new modalities of treatment are clearly needed. Active immunotherapy based on the injection of autologous dendritic cells (DC) co-cultured ex vivo with tumor antigens has been used in pilot studies in various malignancies such as melanoma and lymphoma with encouraging results.

Methods: In the present paper, the preparation and exposure of patient DC to autologous HCC antigens and re-injection in an attempt to elicit antitumor immune responses are described.

Lentiviral vector-mediated tyrosinase-related protein 2 gene transfer to dendritic cells for the therapy of melanoma.

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs), which play a vital role in primary immune responses. Introducing genes into DCs will allow constitutive expression of the encoded proteins and thus prolong the presentation of the antigens derived therefrom. In addition, multiple and unidentified epitopes encoded by the entire tumor-associated antigen (TAA) gene may enhance T cell activation.

John Kerr and apoptosis.

On 14 March 2000, John Foxton Ross Kerr, Emeritus Professor of Pathology at the University of Queensland, received the Paul Ehrlich and Ludwig Darmstaedter Prize for his description of apoptosis, a form of cell death. The prize, which he shared with Boston biologist Robert Horvitz, is considered to be one of the most prestigious European awards in science, second only to the Nobel Prize.

Development of disabled, replication-defective gene transfer vectors from the Jembrana disease virus, a new infectious agent of cattle.

Jembrana disease virus (JDV) is a newly isolated and characterised bovine lentivirus. It causes an acute disease in Bali cattle (Bos javanicus), which can be readily transmitted to susceptible cattle with 17% mortality. There is as yet no treatment or preventive vaccine.

Increased cell surface protease activity in UV-irradiated cells undergoing apoptosis.

UVB-irradiated HeLa cells undergoing apoptosis have increased cell surface protease (CSP) activity compared to viable or necrotic cells. In order to elucidate whether caspase 3 plays a role in the activation of CSP in cells undergoing apoptosis, HeLa cell cultures were pre-treated with the caspase inhibitor, DEVD, prior to being exposed to 500 Jm(-2) UVB. DEVD significantly inhibited caspase 3 activity in cells undergoing apoptosis, but did not affect the activation of CSP in these cells.

Novel bovine lentiviral vectors based on Jembrana disease virus.

Background: Safety is a concern that must be addressed prior to any clinical use of human immunodeficiency virus (HIV)-based lentiviral vectors in human patients. Unfortunately, efforts to examine the biosafety of the vectors in preclinical animal models are hampered due to the lack of animal models for HIV infection. We have developed new lentiviral vectors based on the recently characterised Jembrana Disease Virus (JDV), which infects a specific species of cattle naturally in Bali, Indonesia.