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
June 11,2020

The World Health Organisation (WHO) Director-General Tedros Adhanom Ghebreyesus said that more research needs to be done to better understand the extent to which COVID-19 is being spread by people who don't show symptoms.

"Since early February, we have said that asymptomatic people can transmit COVID-19, but that we need more research to establish the extent of asymptomatic transmission," the WHO chief said at a virtual press conference from Geneva on Wednesday, Xinhua news agency reported.

"That research is ongoing, and we're seeing more and more research being done," he added.

Saying that the world has been achieving a lot in knowing the new virus, the WHO chief told reporters that "there's still a lot we don't

"WHO's advice will continue to evolve as new information becomes available," he said.

Tedros stressed that the most critical way to stop transmission is to find, isolate and test people with symptoms, and trace and quarantine their contacts.

"Many countries have succeeded in suppressing transmission and controlling the virus doing exactly this," Tedros said.

Meanwhile, Michael Ryan, executive director of WHO Health Emergencies Program, said Wednesday that the COVID-19 pandemic is still evolving.

"If we look at the numbers... this pandemic is still evolving. It is growing in many parts of the world," he said. "We have deep concerns that health systems of some countries are struggling, under a huge strain and require our support, our help and our solidarity."

He said "each and every country has a different combination of risks and opportunities, and it's really down to national authorities to carefully consider where they are in the pandemic."

In Europe, the risk issue now are about travels and the opening of the schools, around risk management, mass gathering, surveillance and contact tracing, said the WHO official.

In Southeast Asian countries, where to a great extent transmissions have been under control, governments are more concerned about the re-emergence of clusters, while in South America, the issue of PPE for health workers has not gone away, said Ryan.

As regards Africa, Ryan said the death rates have been very low in the past week, but the health system can be overwhelmed, as it would have to cope with other diseases such as malaria.

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Agencies
April 21,2020

The Lockdown is not a cure but a critical strategy to prevent the geographical spread of COVID-19.

While pandemics at this level involves actual life threatening situations for individual's or significant others in one's immediate circle, it envisages a marked disruption in routine life. Even after the pandemic has been contained and will come to pass; it's aftermath will leave a trailblazer which demands planning and implementation of a post pandemic reconstruction of society with potentially traumatic experiences varying in intensity, multiplicity and duration.

Degree of Trauma

It would do well for each one of us to realise that the pandemic is "potentially traumatic", since not everyone will experience COVID -19 as a traumatic event in their lives. Yet, there will be those who may develop post pandemic stress reactions, depression and related dysfunction and pathological reactions while still other exhibit healthy reactions to the same set of circumstances.

"Psychological reactions to the pandemic can be distilled into four distinct prototypical patterns, namely, Resilience, Recovery, Chronic and Delayed patterns which may vary in intensity, multiplicity, and duration. Resilient individual have an ability to bounce back from adversity and experience modest or little disruption in normal functioning and are able to maintain a relatively stable, healthy levels of psychological functioning even after enduring the pandemic. Recovery pattern is characterised by relatively rapid reduction in symptoms and return to normal functioning whereas chronic pattern is characterised by symptoms and dysfunction of a long duration," says Pune-based military psychologist Lt Col Dr Samir Rawat.

Challenges at the Individual and Community Levels

From a psychological perspective, post pandemic reconstruction would entail catering to the problems, concerns and needs of those adversely impacted by the COVID -19 with stress symptoms typically characterised by individual's experiencing an overwhelming trauma of the pandemic (for example, recurring nightmares/ breaking into a cold sweat, flashback of stressful events, increasing irritability, low frustration tolerance or emotional numbing).

It could also manifest in depressive symptoms which may result in lack of interest or diminished pleasure in activities and things which you earlier liked to do, feelings of worthlessness or even survivor guilt in case of a loss of a loved one due to COVID-19, fleeting thoughts of death and suicidal ideation. Physical symptoms, on the other hand could be a decrease in appetite, weight and sleep problems, inability to focus and lack of concentration.

Undoubtedly, the pandemic will cause a financial loss of varying magnitude to many, especially the marginalised and economically disadvantaged strata of daily wage earners; it will also lead to loss of jobs (already beginning to show), homelessness, occupational difficulties and new challenges in interpersonal relations at work and on the home front, besides physical health problems and psychological barriers with new norms of accepted social behaviour (social distancing, handshakes, an obsession for cleanliness to name a few).

Emotional battles

Many factors may influence whether individuals come out stronger and more resilient or surrender to the pandemic. Emotion Regulation is one such long term critical factor that can play an important role in contributing to varying degrees of adaptation with negative or positive outcomes. While we know that primary emotions are fear, anger, disgust, joy, anticipation, acceptance, sadness and surprise, other basic emotions include wonder, love, desire, joy, hatred, sadness, attachment, disgust, rage and even expectancy .

To be able to regulate these emotions and avoid negativity , especially on social media platforms is likely to increase efforts in emotion regulation which involves initiating, increasing or maintaining an emotional response.

This means by regulating or on the other hand by stopping, decreasing or avoiding an emotional response, that is, by down-regulating, depending on the individual's objectives and goals or his /her ability to regulate emotions in the valued and given direction.

"One of the best ways to regulate emotions is through cognitive restructuring wherein we change the way we think; after all it is not the event but the interpretation of the event which is perceived as stressful and finding meaning promotes resilience and reduces risk and vulnerability to stress," advises Dr Rawat.

Adding, "Clearly, we need to have a psychological plan to prevent, mitigate and minimise negative outcomes by post pandemic reconstruction of society at an individual and community level all over the country; this has to be integrated by all leaders across verticals in diverse domains."

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