The new Diploma of Rural Generalist Anaesthesia: Supporting Australian rural and remote communities.

In 2023, a Diploma of Rural Generalist Anaesthesia (DipRGA) was implemented across Australia. Developed collaboratively by the Australian and New Zealand College of Anaesthetists (ANZCA), the Australian College of Rural and Remote Medicine (ACRRM) and the Royal Australian College of General Practitioners (RACGP), the 12-month qualification is completed during or following ACRRM or RACGP Rural Generalist Fellowship training. Focused on the needs of rural and remote communities for elective and emergency surgery, maternity care, resuscitative care for medical illness or injury, and stabilisation for retrieval, the DipRGA supports rural generalist anaesthetists working within collaborative teams in geographically isolated settings.

Proteome-wide structural changes measured with limited proteolysis-mass spectrometry: an advanced protocol for high-throughput applications.

Proteins regulate biological processes by changing their structure or abundance to accomplish a specific function. In response to a perturbation, protein structure may be altered by various molecular events, such as post-translational modifications, protein-protein interactions, aggregation, allostery or binding to other molecules. The ability to probe these structural changes in thousands of proteins simultaneously in cells or tissues can provide valuable information about the functional state of biological processes and pathways.

Compounds activating VCP D1 ATPase enhance both autophagic and proteasomal neurotoxic protein clearance.

Enhancing the removal of aggregate-prone toxic proteins is a rational therapeutic strategy for a number of neurodegenerative diseases, especially Huntington's disease and various spinocerebellar ataxias. Ideally, such approaches should preferentially clear the mutant/misfolded species, while having minimal impact on the stability of wild-type/normally-folded proteins. Furthermore, activation of both ubiquitin-proteasome and autophagy-lysosome routes may be advantageous, as this would allow effective clearance of both monomeric and oligomeric species, the latter which are inaccessible to the proteasome.

Mechanistic Insights into a CDK9 Inhibitor Via Orthogonal Proteomics Methods.

Cyclin-dependent-kinases (CDKs) are members of the serine/threonine kinase family and are highly regulated by cyclins, a family of regulatory subunits that bind to CDKs. CDK9 represents one of the most studied examples of these transcriptional CDKs. CDK9 forms a heterodimeric complex with its regulatory subunit cyclins T1, T2 and K to form the positive transcription elongation factor b (P-TEFb).

The Lipopolysaccharide-Sensing Caspase(s)-4/11 Are Activated in Cirrhosis and Are Causally Associated With Progression to Multi-Organ Injury.

Background And Aims: The development of multi-organ injury in cirrhosis is associated with increased intestinal permeability, translocation of gut-derived bacterial products [e.g., lipopolysaccharide (LPS)] into the circulation, and increased non-apoptotic hepatocyte cell death.

A machine learning-based chemoproteomic approach to identify drug targets and binding sites in complex proteomes.

Chemoproteomics is a key technology to characterize the mode of action of drugs, as it directly identifies the protein targets of bioactive compounds and aids in the development of optimized small-molecule compounds. Current approaches cannot identify the protein targets of a compound and also detect the interaction surfaces between ligands and protein targets without prior labeling or modification. To address this limitation, we here develop LiP-Quant, a drug target deconvolution pipeline based on limited proteolysis coupled with mass spectrometry that works across species, including in human cells.

Identifying breast cancer patients who gain the most dosimetric benefit from deep inspiration breath hold radiotherapy.

Introduction: Deep inspiration breath hold (DIBH) has been proven to reduce cardiac dose for women receiving left breast and chest wall radiation therapy. However, it utilises extra departmental resources and patient exertion. The aim of this exploratory study was to investigate if any factors existed that could identify breast cancer patients who may benefit most from DIBH, to facilitate appropriate utilisation of departmental resources.

Deep inspiration breath hold in breast cancer: Development and analysis of a patient experience questionnaire.

Introduction: Evidence that Deep Inspiration Breath Hold (DIBH) can reduce cardiac dose during left-sided breast radiation therapy (RT) has led to widespread uptake of this technology. There is a paucity of published information documenting the impact of this technique on the patient's treatment experience. The aim of this study was to develop a tool to assess the patient's experience with the introduction of DIBH using the Elekta Active Breathing Coordinator (ABC) in a single institution.

Characterising knotting properties of polymers in nanochannels.

Using a lattice model of polymers in a tube, we define one way to characterise different configurations of a given knot as either "local" or "non-local", based on a standard approach for measuring the "size" of a knot within a knotted polymer chain. The method involves associating knot-types to subarcs of the chain, and then identifying a knotted subarc with minimal arclength; this arclength is then the knot-size. If the resulting knot-size is small relative to the whole length of the chain, then the knot is considered to be localised or "local"; otherwise, it is "non-local".

Bioinspired detoxification of blood: The efficient removal of anthrax toxin protective antigen using an extracorporeal macroporous adsorbent device.

Whilst various remedial human monoclonal antibodies have been developed to treat the potentially life-threatening systemic complications associated with anthrax infection, an optimal and universally effective administration route has yet to be established. In the later stages of infection when antibody administration by injection is more likely to fail one possible route to improve outcome is via the use of an antibody-bound, adsorbent haemoperfusion device. We report here the development of an adsorbent macroporous polymer column containing immobilised B.

Hepatocellular differentiation status is characterized by distinct subnuclear localization and form of the chanzyme TRPM7.

The channel-kinase TRPM7 is important for the survival, proliferation, and differentiation, of many cell types. Both plasma membrane channel activity and kinase function are implicated in these roles. Channel activity is greater in less differentiated hepatoma cells compared with non-dividing, terminally differentiated adult hepatocytes, suggesting differences in protein expression and/or localization.

A haemocompatible and scalable nanoporous adsorbent monolith synthesised using a novel lignin binder route to augment the adsorption of poorly removed uraemic toxins in haemodialysis.

Nanoporous adsorbents are promising materials to augment the efficacy of haemodialysis for the treatment of end stage renal disease where mortality rates remain unacceptably high despite improvements in membrane technology. Complications are linked in part to inefficient removal of protein bound and high molecular weight uraemic toxins including key marker molecules albumin bound indoxyl sulphate (IS) and p-cresyl sulphate (PCS) and large inflammatory cytokines such as IL-6. The following study describes the assessment of a nanoporous activated carbon monolith produced using a novel binder synthesis route for scale up as an in line device to augment haemodialysis through adsorption of these toxins.

Regional health workforce planning through action research: lessons for commissioning health services from a case study in Far North Queensland.

Creating a stable and sustainable health workforce in regional, rural and remote Australia has long been a challenge to health workforce planners, policy makers and researchers alike. Traditional health workforce planning is often reactive and assumes continuation of current patterns of healthcare utilisation. This demonstration project in Far North Queensland exemplifies how participatory regional health workforce planning processes can accurately model current and projected local workforce requirements.

TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling.

Objective: Failure to properly dispose of glucose in response to insulin is a serious health problem, occurring during obesity and is associated with type 2 diabetes development. Insulin-stimulated glucose uptake is facilitated by the translocation and plasma membrane fusion of vesicles containing glucose transporter 4 (GLUT4), the rate-limiting step of post-prandial glucose disposal.

Methods: We analyzed the role of Tusc5 in the regulation of insulin-stimulated Glut4-mediated glucose uptake in vitro and in vivo.

Advanced rural skills training: are recently qualified GPs using their procedural skills?

Introduction: The number of GPs providing procedural services in rural areas is declining; however, few studies have investigated issues directly relevant to recently qualified doctors. Limited published data and anecdotal reports in Australia suggest that a large proportion of doctors leave rural procedural practice soon after training. This study aimed to: (1) describe where GPs practice in the 5 years after advanced rural skills training; (2) describe the proportion of doctors using their advanced skills; (3) measure doctors' ratings of the quality of support and how critical the year directly following training is in future career choices; and (4) measure the association between support and use of advanced skills.

Supporting GP advanced rural skills training.

Objective: The aim of this study was to: investigate doctors' experiences of support during GP advanced rural skills training, and identify strategies to improve support.

Design: The qualitative responses from a cross-sectional, postal survey are reported.

Setting: Rural vocational training sector.

TaqIA polymorphism in dopamine D2 receptor gene complicates weight maintenance in younger obese patients.

Objective: The A1 allele of the TaqIA polymorphism in the dopamine D2 receptor gene (rs1800497) has been associated with obesity. However, the effect of the polymorphism on the success in weight loss and/or weight maintenance during weight-loss programs has not been evaluated thus far.

Methods: The rs1800497 was genotyped in 202 (135 female, 67 male) severely obese individuals with an initial body mass index of 41.

Regulation of adipocyte formation by GLP-1/GLP-1R signaling.

Increased nutrient intake leads to excessive adipose tissue accumulation, obesity, and the development of associated metabolic disorders. How the intestine signals to adipose tissue to adapt to increased nutrient intake, however, is still not completely understood. We show here, that the gut peptide GLP-1 or its long-lasting analog liraglutide, function as intestinally derived signals to induce adipocyte formation, both in vitro and in vivo.

Adipogenesis and insulin sensitivity in obesity are regulated by retinoid-related orphan receptor gamma.

Obesity is a well-known risk factor for the development of secondary complications such as type 2 diabetes. However, only a part of the obese population develops secondary metabolic disorders. Here, we identify the transcription factor retinoid-related orphan receptor gamma (RORγ) as a negative regulator of adipocyte differentiation through expression of its newly identified target gene matrix metalloproteinase 3.

A tale of three hospitals: solving learning and workforce needs together.

Major developments in medical education in Australia include increasing the numbers of students and educating more students within the community and in regional, rural and remote settings. Rapid growth of student numbers and the rural orientation of the James Cook University medical school course has meant that northern Queensland had to deal with these issues earlier than other regions. One solution has been to transform some rural hospitals into teaching health services.

Regionalisation of rural medical training in far north Queensland: a learning experience for medical educators and managers.

The need for an appropriate, dedicated vertically-integrated training pathway for rural doctors, provided by regional consortia of educational organisations, has been clearly identified by Rural Doctors Association of Queensland (RDAQ) and The Australian College of Rural and Remote Medicine (ACRRM) as a key strategy to resolve rural medical workforce issues. The opportunity to put the ideas into action is now here with rural doctors responding to the challenge of managing more reform in general practice all over Australia. In Far North Queensland, the ongoing reform of general practice education has been challenging, with many lessons learned by both educators and managers.

Good luck and good management: the miracle escape.

This case study illustrates the importance of education and training in the early management of reverse trauma in the rural setting. It clearly demonstrates the importance of ensuring a safe approach including an outline for the appropriate management of electrocution.