Scientists crack insulin mystery, may see end of needles

January 11, 2013

Melbourne, Jan 11: In a major breakthrough that could help millions of diabetics, Australian researchers have solved a 20-year mystery that could which could spell the end of daily injections.

The new knowledge on how insulin works at a molecular level could be exploited to develop improved insulin medications to treat both type 1 and type 2 diabetes, they said.

Researchers from the Walter and Eliza Hall Institute of Medical Research have captured the first three-dimensional images of insulin "docking" to its receptor, a mystery scientists have been trying to solve for two decades.

Previously, scientists remained unsure as to how insulin binds to the receptor on the surface of cells to allow them to take up sugar from the blood and transform it into energy.

The international research team was led by scientists from the Walter and Eliza Hall Institute (WEHI) in Melbourne, with collaborators from La Trobe University, the University of Melbourne, Case Western Reserve University, the University of Chicago, the University of York and the Institute of Organic Chemistry and Biochemistry in Prague.

Lead researcher Mike Lawrence, an Associate Professor at the institute's Structural Biology division said: "This discovery could conceivably lead to new types of insulin that could be given in ways other than injection, or an insulin that has improved properties or longer activity so that it doesn't need to be taken as often. It may also have ramifications for diabetes treatment in developing nations, by creating insulin that is more stable and less likely to degrade when not kept cold, an angle being pursued by our collaborators. Our findings are a new platform for developing these kinds of medications,"

Lawrence said the insulin is a key treatment for diabetics, but there are many ways that its properties could potentially be improved, the Gizmag website reported.

"Understanding how insulin interacts with the insulin receptor is fundamental to the development of novel insulins for the treatment of diabetes. Until now we have not been able to see how these molecules interact with cells. We can now exploit this knowledge to design new insulin medications with improved properties, which is very exciting," he said.

The Assoc professor said the team was excited to reveal for the first time a three-dimensional view of insulin bound to its receptor.

The study was published in the journal Nature on January 9.

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Agencies
June 17,2020

Leading physicians are celebrating a small dose of good news that arrived Tuesday about dexamethasone, a cheap and widely used steroid shown to be able to save lives among COVID-19 patients, but also cautioning against releasing study results by press release during a global health emergency, like in the case of the latest dexamethasone study by University of Oxford.

"It will be great news if dexamethasone, a cheap steroid, really does cut deaths by one-third in ventilated patients with COVID19, but after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper", Atul Gawande, surgeon and CEO of Haven Healthcare, tweeted.

"Bottom line is, good news," Dr. Fauci, America's foremost infectious diseases expert told a US newswire on Tuesday, soon after the dexamethasone results were announced in the UK.

Fauci, who has long championed the therapeutics-first view said that dexamethasone is a "significant improvement" in the available therapeutic options currently available.

On Medical Twitter and Facebook, doctors broadly agree that dexamethasone use aligns well with the way COVID19 attacks the body's immune system. Fauci said the results in the Oxford study make "perfect sense" in that context.

"We should see the number of people who actually survive go up, if the study holds up," virologist and epidemiologist Dr. Joseph Fair told a television network.

Global coronavirus cases crossed 8 million on Tuesday. In the US, Texas and Florida are facing a new wave of cases after lifting lockdown orders earlier than medical experts recommended. Amidst the relentless graph upwards, the dexamethasone study results injected hope for better survival rates among those most seriously ill.

World Health Organization chief scientist Soumya Swaminathan welcomed the results from the randomised control trial.

Dr Eugene Gu, Founder and CEO of CoolQuit tweeted that he is "genuinely impressed" with the UK dexamethasone trial. This may be a "game changer", he wrote.

"There's no conflict of interest as dexamethasone is a generic steroid. The mechanism of action makes sense because steroids can reduce cytokine storms and overactive immune systems that makes COVID-19 so deadly. The number needed to treat is 8 ventilated patients which is great."

The Oxford study found that dexamethasone reduced deaths by 35 percent in patients who needed treatment with breathing machines and by 20 percent in those only needing supplemental oxygen. Dexamethasone was one of 5 drugs studied in a large clinical trial in the United Kingdom named RECOVERY, short for Randomised Evaluation of COVID-19 Therapy.

Peter Horby, chief investigator of the University of Oxford clinical trial, said dexamethasone is the first drug to be shown to improve survival in COVID-19. Details of the study have not been released. The trial organisers said they made their announcement via a news release because of "the public health importance of these results." According to Horby's public comments, there was a lot of initial resistance to studying steroids.

During the study, 2,104 patients were randomly selected to be given 6 milligrams of dexamethasone once a day (either by mouth or by intravenous injection) for 10 days. That group was compared with 4,321 patients who received the usual care alone.

Researchers estimated that dexamethasone would prevent one death for every eight patients treated while on ventilators and one for every 25 patients on extra oxygen alone.

UK experts have called the study results a breakthrough in the fight against the virus. The researchers have promised they would publish the results soon.

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Agencies
July 7,2020

The World Health Organization (WHO) is reviewing a report that suggested its advice on the novel coronavirus needs updating after some scientists told the New York Times there was evidence the virus could be spread by tiny particles in the air.

The WHO says the Covid-19 disease spreads primarily through small droplets, which are expelled from the nose and mouth when an infected person breaths them out in coughs, sneezes, speech or laughter and quickly sink to the ground.

In an open letter to the Geneva-based agency, 239 scientists in 32 countries outlined the evidence they say shows that smaller exhaled particles can infect people who inhale them, the newspaper said on Saturday.

Because those smaller particles can linger in the air longer, the scientists - who plan to publish their findings in a scientific journal this week - are urging WHO to update its guidance, the Times said.

"We are aware of the article and are reviewing its contents with our technical experts," WHO spokesman Tarik Jasarevic said in an email reply on Monday to a Reuters request for comment.

The extent to which the coronavirus can be spread by the so-called airborne or aerosol route - as opposed to by larger droplets in coughs and sneezes - remains disputed.

Any change in the WHO's assessment of the risk of transmission could affect its current advice on keeping one-metre physical distancing. Governments, which also rely on the agency for guidance policy, may also have to adjust public health measures aimed at curbing the spread of the virus.

"Especially in the last couple of months, we have been stating several times that we consider airborne transmission as possible but certainly not supported by solid or even clear evidence," Benedetta Allegranzi, the WHO's technical lead for infection prevention and control, was quoted as saying in the New York Times.

WHO guidance to health workers, dated June 29, says that SARS-CoV-2, the virus that causes Covid-19, is primarily transmitted between people through respiratory droplets and on surfaces.

But airborne transmission via smaller particles is possible in some circumstances, such as when performing intubation and aerosol-generating procedures, it says.

Medical workers performing such procedures should wear heavy-duty N95 respiratory masks and other protective equipment in an adequately ventilated room, the WHO says.

Officials at South Korea's Centers for Disease Control said on Monday they were continuing to discuss various issues about Covid-19, including the possible airborne transmission. They said more investigations and evidence were needed.

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Agencies
February 10,2020

Washington D.C, Feb 10: Children's vulnerability towards depression, anxiety, impulsive behaviour, and poor cognitive performance could be determined by considering the hours of sleep they manage to get.

Sleep states are active processes that support the reorganisation of brain circuitry. This makes sleep especially important for children, whose brains are developing and reorganising rapidly.

In a study by researchers from the University of Warwick -- recently published in the journal Molecular Psychiatry -- cases of 11,000 children aged between 9 and 11 years from the Adolescent Brain Cognitive Development dataset were analyzed to find out the relationship between sleep duration and brain structure.

The study was carried out by researchers Professor Jianfeng Feng, Professor Edmund Rolls, Dr. Wei Cheng and colleagues from the University of Warwick's Department of Computer Science and Fudan University.

Measures of depression, anxiety, impulsive behaviour and poor cognitive performance in the children were associated with shorter sleep duration. Moreover, the depressive problems were associated with short sleep duration one year later.

The reduced brain volume of areas such as orbitofrontal cortex, prefrontal, and temporal cortex, precuneus, and supramarginal gyrus was found to be associated with the shorter sleep duration.

Professor Jianfeng Feng, from the University of Warwick's Department of Computer Science, comments: "The recommended amount of sleep for children 6 to 12 years of age is 9-12 hours. However, sleep disturbances are common among children and adolescents around the world due to the increasing demand on their time from school, increased screen time use, and sports and social activities."

A previous study showed that about 60 per cent of adolescents in the United States receive less than eight hours of sleep on school nights.

Professor Jianfeng Feng further added: "Our findings showed that the total score for behavior problems in children with less than 7 hours sleep was 53 per cent higher on average and the cognitive total score was 7.8 per cent lower on average than for children with 9-11 hours of sleep. It highlights the importance of enough sleep in both cognition and mental health in children."

Professor Edmund Rolls from the University of Warwick's Department of Computer Science also commented: "These are important associations that have been identified between sleep duration in children, brain structure, and cognitive and mental health measures, but further research is needed to discover the underlying reasons for these relationships."

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