Making therapeutic insulin more effective

An international collaboration co-led by researchers at the Walter and Eliza Hall Institute has made a discovery that could make therapeutic insulins more effective by better mimicking the way insulin works in the body. Published in Nature Communications, the study reveals the first definitive three-dimensional (3D) image of how insulin successfully interacts with its receptor in a process that is crucial for instructing cells to lower blood sugar levels in the body. Understanding exactly what this process looks like could inform the design of faster-acting and longer-lasting insulin therapies. It is well established that insulin instructs cells to lower blood sugar levels in the body by binding to a receptor that is located on the cell surface, but nobody knew precisely what was occurring during the interaction. “We have produced the first definitive 3D image of the way in which insulin binds to the surface of cells in order to successfully transmit the vital instructions needed for taking up sugar from the blood,” said the researchers. The detailed image was the outcome of a collaboration between structural and cell biology experts from the Institute, working together with both cryo-electron microscopy specialists at the European Molecular Biology Laboratory in Heidelberg, Germany, and an insulin receptor specialist from the University of Chicago in the US. The findings mean it may now be possible to design insulin therapies that more closely mimic the body’s own insulin.

Brain cooling after traumatic head injury does not improve outcomes

Researchers from Monash University have found that cooling patients’ brains after traumatic head injury does not improve outcomes, compared with patients who did not undergo brain cooling. There has long been controversy around the benefits of brain cooling in the intensive care unit after a traumatic brain injury (TBI), in the belief that cooling, or hypothermia, reduces brain inflammation and consequent brain damage. Many laboratory studies support brain cooling after head injury, and the majority of clinical studies and the clinical TBI guidelines all report benefit for patients. However, many doctors remain skeptical about cooling because almost all clinical studies to date were not high quality, the better studies had limitations, and hypothermia requires special expensive equipment and has known complications. The researchers looked at 511 patients with TBI in six countries – France, Switzerland, Qatar, Saudi Arabia, Australia and New Zealand – and found that the percentage of patients with favourable neurological outcomes 6 months after brain trauma treated using cooling was almost exactly the same as in patients who had their temperature controlled to normal instead (48.8% v 49.1%). Favourable neurological outcome was defined as Glasgow Outcome Scale – Extended (GOS-E) of 5–8 (a GOS-E score of 1 indicates death, 2 indicates vegetative state, 3–4 indicates severe disability, 5–6 indicates moderate disability, and 7–8 indicates good recovery). Mortality at 6 months was 21.4% in patients with hypothermia, and 18.4% in those with a normal temperature target. Adjusting the data for the severity of the TBI and analysis of specific patient subgroups made no difference to the results. The POLAR trial was presented at the annual meeting of the European Society of Intensive Care Medicine and published simultaneously in JAMA.

Infant gut flora gives insights into disease

US-led research has tested over 20 000 stool samples to look at how the microbiome changes over time, and to investigate associations between the microbiome, infant development and the potential impact of type 1 diabetes. The Environmental Determinants of Diabetes in the Young (TEDDY) study is investigating this relationship and has generated one of the largest datasets on the infant microbiome to date, spanning samples from six clinical centres in the US, Sweden, Germany and Finland. In the first of two articles published in Nature, the researchers used gene sequencing to analyse 12 500 stool samples from 903 children, collected monthly from children aged 3–46 months. Microbiome composition and diversity changed over time in three distinct phases: the developmental phase (3–14 months), transitional phase (15–30 months) and stable phase (31 months onward). During the developmental stage, breastfeeding was associated with higher levels of Bifidobacterium, whereas microbiome diversity increased after weaning, as the infants consumed a greater variety of foods. Vaginal birth was associated with a temporary increase in Bacteroides, which in turn was associated with increased gut diversity and maturation (regardless of birth mode). Siblings, exposure to pets, and geographical location were also factors in differences between microbiome profiles. In the second article, researchers analysed nearly 11 000 stool samples from 783 infants in the TEDDY study to characterise the early gut microbiome in children progressing to type 1 diabetes. They report that the microbiomes of infants without type 1 diabetes harbour more genes related to fermentation and short-chain fatty-acid synthesis that, in combination with previous evidence, are associated with a protective effect. The authors highlight that the infants sampled (mostly non-Hispanic white and at high risk of type 1 diabetes) may not represent other populations.

Hallucinations associated with brain hyperactivity in people with macular degeneration

New research from the University of Queensland has shown for the first time that visual hallucinations in people with macular degeneration (MD) are associated with abnormally heightened activity in the visual cortex of the brain. The findings, published in Current Biology, could improve diagnosis of such hallucinations. Many people who develop MD go on to develop a condition known as Charles Bonnet Syndrome, in which they experience hallucinations as the brain adjusts to significant vision loss. The hallucinations can be simple geometric patterns, or much more complex scenes involving animals, people and places. Researchers stimulated the peripheral visual fields of study participants and found that individuals with hallucinations do indeed show significantly heightened activity in particular parts of their visual system. “The main finding is that when we drive activity in the visual system of people with macular degeneration who report experiencing hallucinations, there is a huge visual response compared with participants who have the same visual loss but don’t have the hallucinations,” the researchers said. “What our results say is that the brains of those reporting hallucinations are more excitable, but it still remains unclear how that excitability is then translated into hallucinations – that’s a question for future research.” The findings could help reduce misdiagnosis of hallucinations in people with MD.

HIV research boosted by $500 000 grant

The Kirby Institute, in partnership with ViiV Healthcare, have announced a new grant to support HIV research capacity building in the Asia-Pacific region. The 3-year program will award over half a million dollars to support healthcare professionals to address national HIV priorities. The unconditional education grant makes possible a research and training program initially proposed by the late Professor David Cooper, foundation Director of the Kirby Institute and one of the world’s most distinguished HIV clinicians and academic leaders. The Cooper HIV/AIDS Research Training (CHART) Program will increase the number of skilled and experienced HIV researchers in the Asia-Pacifc and identify ways to address local HIV priorities. The Kirby Institute will implement the CHART Program in partnership with the World Health Organization’s Special Programme for Research and Training in Tropical Disease (TDR). The Kirby Institute’s training model closely aligns with TDR’s Structured Operational Research and Training Initiative (SORT IT), and the CHART Program will include support from facilitators from the TDR’s global network of accredited mentors in the region. Nine healthcare professionals involved in HIV management will be selected annually from a range of countries in the region. All participants will work on HIV research questions that fit with national HIV priorities. The grant is expected to support three consecutive 12-month training courses to be conducted across 2019–2021.

What’s new online at the MJA

29 October Guideline summary: Revised Australian national guidelines for colorectal cancer screening: family history
Jenkins et al; doi: 10.5694/mja18.00142
The revised colorectal cancer screening guidelines recommend screening modality based on risk according to age and family history … FREE ACCESS for 1 week

29 October Perspective: Ensuring safety in public playgrounds: everybody’s business
Barker et al; doi: 10.5694/mja18.00549
Children need outdoor play but safety standards alone will never prevent all injuries; robust data are required to guide risk minimisation strategies … FREE ACCESS for 1 week

29 October Podcast with Dr Lisa Sharwood, injury epidemiologist  … FREE ACCESS permanently

29 October Podcast with Professor Annemarie Hennessy, AM, Dean of the School of Medicine at Western Sydney University, and an obstetrics and renal physician, talking about preeclampsia … FREE ACCESS permanently


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