Monthly Archives: September 2021

Scientists have also studied the nighttime rituals of another autism model: zebrafish (Danio rerio). Gene-editing techniques enable scientists to create zebrafish with autism-linked mutations, and then they can easily assess how the mutations effect behavior. We can take our fish larvae at 5 days old they have this complex range of behaviors we can easily pipette them into the wells of a 96-well plate, and then track different aspects of their locomotor activity, Hoffman says. The design offers the high throughput and easy replicability of a cell culture study, with the ability to gauge effects on animal behavior.

As a postdoctoral researcher, Hoffman tracked the behavior of 5-day-old zebrafish larvae lacking the autism-linked gene CNTNAP2 and found that they are hyperactive at night. The fish also have fewer-than-usual inhibitory neurons, which dampen neural activity, in the forebrain, replicating findings in mice lacking the same gene and adding heft to the relevance of the fish as an autism model.

Zebrafish are a useful tool for screening potential drugs for autism because chemical compounds can be added directly to the water the fish swim in. In their CNTNAP2 study, published in 2016, Hoffman and her colleagues tested the effects of 14 drugs on the larvae and showed that certain forms of the hormone estrogen can reverse the larvaes hyperactive behavior.

The animals are small and relatively inexpensive, so the team can use them to study the effects of many autism-linked genes in parallel. Hoffmans team is looking at brain activity, movement and sleep-wake cycles across multiple lines of zebrafish with mutations in the fish equivalents of 10 autism-linked genes, including CHD8, CNTNAP2, DYRK1A, GRIN2B and SCN2A. The researchers aim to identify shared characteristics across strains and to identify drugs that could reverse alterations in their behavior.

The CNTNAP2 zebrafish developed in Hoffmans lab are slated to appear on a list of validated zebrafish models curated by the Simons Foundation Autism Research Initiative (SFARI). (Spectrum is an editorially independent publication funded by SFARI.) The goal of that list is to make zebrafish research more reliable by steering researchers toward models that pass a test of genetic quality, says SFARI senior scientist Brigitta Gundersen.

Its all a matter of matching your question to the advantages and disadvantages of your model system. Ethan Scott

Zebrafish larvae have another advantage: They are transparent for the first several days of life. As a result, researchers can see the larvaes internal organs, including the gut, enabling them to visualize the effects of autism mutations on gut function, which is often disrupted in autism. In the larvae, researchers can observe the rhythmic movements of the gut muscles, and food moving through the digestive system. Things play out right in front of you, says Julia Dallman, associate professor of biology at the University of Miami in Coral Gables, Florida.

In studies published in 2019 and 2020, Dallmans team showed that the gut muscles contract, and food moves through the gut, unusually slowly in zebrafish with mutations in SYNGAP1 or SHANK3. In people, mutations in these genes are linked to both autism and gastrointestinal distress, including constipation and acid reflux. When we initially set out to look at gut function in these models, my expectation was that [alterations] would be subtle, Dallman says. Its not subtle at all. Her teams studies suggest that slightly different mechanisms underlie gut problems in the two fish strains, so treatment of constipation in autism may not be one size fits all. Dallman plans to test the effects of drugs on both gut function and behavior in the fish, to aid in the search for autism medications that dont worsen constipation, she says.

The transparency of zebrafish larvae also puts early brain development on display. Using specialized microscopes, researchers can visualize the activity of individual neurons and, because the fish are small, simultaneously track the activity of every neuron in the brain. Youre just observing the brain in an intact, alert, behaving, perceiving animal, says Ethan Scott, who studies sensory processing in zebrafish at the University of Queensland in Brisbane, Australia.

Zebrafish have a more similar brain structure to humans than do invertebrate models, Scott says. And although the fish lack a cerebral cortex, the structure at the surface of the human brain, they are useful for studying circuits in other parts of the brain. Its all a matter of matching your question to the advantages and disadvantages of your model system, Scott says.

Scott is using zebrafish larvae with mutations in autism-linked genes to investigate alterations in sensory processing in autism. He and his colleagues are monitoring their brain activity in response to images shown on a computer screen, and to sounds of varying loudness. In a 2020 study, his team showed that zebrafish lacking FMR1, the gene mutated in fragile X syndrome, are hypersensitive to sound. And in four regions of the brain, their neurons react to sound with more frequent or stronger bursts of activity than those in typical fish. The work may help explain sensory hypersensitivity in autism, Scott says.

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What studying worms, flies and fish says about autism - Spectrum

(Precision Vaccinations)

Severe COVID-19 patients tend to have one thing in common: insufficient or defective proteins that help regulate the immune system, known as type I interferons (IFNs), stated researchers with Rockefeller University.

Jean-Laurent Casanova, M.D., Ph.D., previously demonstrated that at least 10% of severe cases could be chalked up to either a genetic condition that cripples IFN production or misguided antibodies that attack those crucial proteins.

Two new studies published in Science Immunology on August 19, 2021, explain how another 10% of severe cases are linked to IFN.

These autoantibodies are found even in uninfected individuals, which suggests that they are a cause, rather than an effect, of severe COVID-19.

We can neatly explain much of severe COVID-19 as a net defect in type I IFN, Casanova stated in a press release.

To an extent never seen for any other acute infectious disease, these four studies collectively provide a molecular and immunological explanation for about 20 percent of critical cases.

The new papers highlight additional IFN-related defects unique to severe and fatal COVID-19 cases.

In the first study, Casanova and colleagues found that 1 to 2% of men under the age of 60 who experience severe COVID-19 have deleterious mutations in TLR7, a gene within the X chromosome involved in the production of type I IFN.

In the second study, the scientists demonstrated that confused antibodies were attacking type I IFNs instead of the virus account for a more significant number of severe cases than previously thought 20% of people who died from COVID-19 had high levels of autoantibodies that specifically target and destroy IFNs.

While they are in only about 0.5% of people under age 60, that number rises to 4% at age 70 and up to 7% by age 85.

These findings, resulting from the collaboration of the COVID Human Genetic Effort, a global international consortium co-led by Casanova, have immediate clinical implications.

First, it is quick and easy to test for auto-Abs against type I IFNs in patients infected with SARS-CoV-2. Screening for these antibodies is even possible in the general population before infection.

Second, patients with auto-Abs against type I IFN should be vaccinated against COVID-19 as a priority.

Third, live attenuated vaccines, including YFV-17D and vaccines using the YFV-17D backbone against SARS-CoV-2, should not be given to patients with auto-Abs.

Fourth, these patients appeared healthy before SARS-CoV-2 infection, but they should also be carefully followed for other viral illnesses, as exemplified by adverse reactions to YFV-17D.

Fifth, in cases of SARS-CoV-2 infection in unvaccinated individuals with auto-Abs against type I IFNs, the patients should be hospitalized for prompt management.

Early treatment with monoclonal antibodies can be administered in patients without symptoms of severe COVID-19 pneumonia, and IFN- can be administered in the absence of both pneumonia and auto-Abs against IFN-. Rescue treatment by plasma exchange is another therapeutic option in patients who already have pneumonia.

Sixth, blood products, especially plasma, should be screened for anti-IFN auto-Abs, and any products containing such antibodies should be excluded from donation. And plasma from donors convalescing from COVID-19 should be tested for such auto-Abs.

Seventh, given the documented innocuity and potential efficacy of a single injection, early therapy with IFN- may be considered for the contacts of contagious subjects or during the first week after infection, even in the absence of, or before the documentation of auto-Abs against type I IFNs, in elderly patients, who have a higher risk of critical pneumonia and auto-Abs against IFN-2 and IFN-, but not IFN-.

Another possibility would be the administration of monoclonal antibodies that can neutralize SARS-CoV-2.

Finally, it will be essential to decipher the mechanism underlying the development of these auto-Abs, which may differ in patients over and under 65 years of age.

Overall, our findings show that auto-Abs neutralizing concentrations of type I IFN lower than previously reported but still higher than physiological concentrations typical in the elderly population.

Notes: The COVID Human Genetic Effort is an international consortium aiming to discover the human genetic and immunological bases of the various clinical forms of SARS-CoV-2 infection.

The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the US NIH, and others. These researchers did not disclose relevant industry conflicts of interest.

PrecisionVaccinations publishes fact-checked research-based vaccine news.

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Seeking the Common Thread in Severe COVID-19 - Precision Vaccinations

Two-day event featured 10% growth in registrations and a wide array of expert stakeholders

INDIANAPOLIS, Sept. 9, 2021 /PRNewswire/ -- hc1, the leader in critical insight, analytics, and solutions for precision health, announced today the successful completion of its 2nd annual Precision Health Virtual Summit. Registrations for this year's event grew by 10%, evidencing a growing interest in the innovations and collaborations ushering in a new era of precision health.

(PRNewsfoto/hc1)

The second Precision Health Virtual Summit saw a 10% increase in registrations, showcasing interest in precision health.

The two-day event held in partnership with Becker's Healthcare featured leading experts including keynote presentations from Katherine Capps, president of Health2 Resources and co-founder and executive director of GTMRx (Get the Medications Right) Institute, and David Nash, MD, MBA, founding dean emeritus of Jefferson College of Population Health at Thomas Jefferson University.

In "Precision Health and Population Health: Friends or Foes," Nash discussed how two of healthcare's priority initiatives can work in tandem to achieve cost, access and clinical outcomes goals. Nash explained how eliminating waste in population health is a driver for precision health and ties into addressing cost and access concerns in delivering individualized care for all patients.

"It's amazing how much is changing and how quickly it is changing. Precision medicine harnessing the human genome and being able to deliver precision, personalized careit's a kissing cousin of population health; it's a subset; it's a pillar. One thing is clear: they are not on a collision course. Quite frankly, they are incredibly complementary," Nash said.

"The field of precision health is moving at light speedthe fastest in history," Jeffrey Kuhlman, MD, General Manager, Healthcare Analytics Solution, AdventHealth, told "Precision Health and Genomics: Unlocking Individuality" session moderator Mackenzie Bean, Writer/Reporter, Becker's Hospital Review. "Think about where we were in 1985 with personal computers and IT. Well, that's actually where we are today with omics and with precision health. Not just the next 25 years we're gonna see those truly amazing changes, but even within the next few years we're gonna see light speed changes. What's needed for that is we've got to develop the clinical decision support tools that allow physicians to easily access what's presented to them, in an easy to understand way, in their workflow, that's actionable that more importantly puts patients at the center of the program."

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In her presentation, "The Future of Precision Health," Capps discussed how personalized medicine and gene therapies are laying the groundwork for better care today and in the future. After providing a real-life account of the medication struggles of a patient with multiple complex conditions, she provided an overview of a new solution called Comprehensive Medication Management (CMM)a method that differs from traditional medication therapy management (MTM) and takes a systematic, integrated and collaborative approach to medications built on an understanding of how genetics influence efficacy through pharmacogenomics.

"The ultimate goal is precision preventative medicine. We believe at the institute that we can move from precise to personalized medicine through the expansion of CMM in the delivery setting through application of knowledge, access to clinical pharmacists, leveraging pharmacogenomics testing. It'll reduce burnout, increase physician, patient satisfaction. It'll lead to better outcomes at a lower cost and it'll ensure that we achieve the quadruple aim," Capps said.

Brad Bostic, Founder, chairman and CEO of hc1, opened the virtual summit with an address that focused on the challenges of healthcare's current one-size-fits-all care delivery model and how data silos create barriers to holistically addressing the needs of individual patients. He also discussed how high-impact technology partnerships are changing this dynamic through a new class of solutions called Precision Health Insight Networks (PHINS).

"I really found it an energizing, exciting opportunity to bring together people from all different parts of the healthcare value chain to talk about how we can solve this challenge of one size fits all trial-and-error care and move to more of a model that's focused on the end outcome of the patient and bringing the most precise possible approach to healthcare," Bostic noted in his closing remarks. "Today we've got about 30% of all healthcare dollars being wasted. In the future, we really need to fix that, and together we can do it. We also see about 128,000 people per year in the U.S. dying from taking medications as prescribed, and with new precision medicine techniques, with better precision approaches to managing health across populations, we can do much, much better and eliminate those unnecessary dollars and unnecessary deaths."

Sponsors of the Precision Health Virtual Summit include AWS, Snowflake and leader sponsor Quest Diagnostics. The event was offered free of charge and can be accessed on-demand at hc1.com/summit.

About hc1hc1 is the leader in critical insight, analytics, and solutions for precision health. The hc1 Precision Health Cloud organizes volumes of live data, including lab results, genomics, and medications, to deliver solutions that ensure that the right patient gets the right test and the right prescription. Today, the hc1 Platform powers solutions that optimize diagnostic testing and prescribing for millions of patients nationally. To learn more about hc1's proven approach to personalizing care while eliminating waste for thousands of health systems, diagnostic laboratories, and health plans, visit http://www.hc1.com and follow us on Twitter, Facebook, and LinkedIn.

Media Contact Liz Goar email: liz@npccs.com phone: 813-333-2844

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2nd Precision Health Virtual Summit Provides Look at Innovation Advancing the Promise of Personalized Medicine - Yahoo Finance

THOUSAND OAKS, Calif., Sept. 9, 2021 /PRNewswire/ --Amgen (NASDAQ: AMGN) will present at Morgan Stanley's 19th Annual Global Healthcare Conference at 2:45 p.m. ET on Tuesday, Sept. 14, 2021. Robert A. Bradway, chairman and chief executive officer at Amgen will present at the conference. Live audio of the conference call will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.

The webcast, as with other selected presentations regarding developments in Amgen's business given at certain investor and medical conferences, can be accessed on Amgen's website, http://www.amgen.com, under Investors. Information regarding presentation times, webcast availability and webcast links are noted on Amgen's Investor Relations Events Calendar. The webcast will be archived and available for replay for at least 90 days after the event.

About AmgenAmgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to beone ofthe world'sleadingindependent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visitwww.amgen.comand follow us onwww.twitter.com/amgen.

CONTACT: Amgen, Thousand OaksMegan Fox, 805-447-1423 (media)Trish Rowland, 805-447-5631 (media)Arvind Sood, 805-447-1060 (investors)

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Amgen to Present at the 19th Annual Morgan Stanley Global Healthcare Conference - StreetInsider.com

Indias genetic diversity is tied to language and social systems rather than geography, says study.  |  Photo Credit: iStock Images

India and its diversity have always been a subject of intrigue to the rest of the world, and a matter of pride for the Indians.

Genetic diversity varies substantially among Indian populations. So much so that at the continental level, the Indian continental group has significantly higher DNA diversity than European and East Asian groups put together.The study of the subcontinents population is of great interest to anthropologists purely because of the sheer size of the Indian population, the complex demographic history, and our unique social structures.

While research in the past has unravelled human genetic variation to a great extent, India's vast reservoir of genetic diversity still has a lot of scope to be explored.

The past genetic analysis of the Indian population had revealed that the diverse groups that we see today in India come from two major ancient populations the Ancestral North Indians (ANI) and the Ancestral South Indians (ASI). Basically establishing that geography is the biggest driver behind the genetic diversity of a population.

However, that is not quite the case, says research from Purdue University. The new study has now indicated that while the geography influencing genetic diversity'theory might stand true for European countries, it is not the case with India.

The study involved a unique model of interdisciplinary research bringing together genetics and computer science to consider jointly many different factors that may have shaped heredities. Using the model the Peristera Paschou, a population geneticist and associate professor of biological sciences at Purdue and Aritra Bose, a doctorate in both data science and genetics analysed a comprehensive dataset that represents the diversity of the Indian subcontinent.

The results opened a range of possibilities that were hitherto unknown. It revealed that in places like India, language and social systems like castes strongly affect how and where people live, implying that our genetic diversity is influenced more than just geography.

To put in perspective, if you know someones genetics among the European population, you can guess where they are from, to within a few kilometres in some cases, and if you know where someones ancestors came from, you have a close approximation of their genetic makeup.

However, in the Indian context, spoken language was seen as a major force in bringing people together in India besides the socio-demographic factors. Simply put, the results threw light on how the Indian people moved into India, and how various groups of people commingled. People who speak the same language (or even similar languages) here tended to be much more closely related, even if they lived far apart geographically.

Now, this model developed to analyse Indias population genetics is significant. Based on this, anthropologists will now be able to study other populations where genetics are not as closely tied to where one lives or hails from. Essentially the non-European populations with rich histories of diversity and migrations.

And this, in turn, will help us understand the history of human movement and cultures. You never know, it might even pave the way to understanding human health and susceptibility to disease, and pave way for advanced medical research where diagnosis and the treatment model will vary with each genetic group.

So, if you are an Indian or an Indian-origin person, dont go about trying to find your ancestors on the internet-based genetic and ancestry services. Those rely on the geography of ones forebears to determine our roots. India is more than just that.

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Indian genetic diversity is more about languages and social systems than just geography, says research - Times Now

Dame Sarah is already on the record as not being a fan of jabbing children for the sake of it. She has pointed out that countries should consider vaccinating the small number most at risk, but otherwise is not convinced of the benefits.

If you cant prevent transmission by vaccination and the children are not at risk of severe disease and hospitalisation and death, which the vast majority of children are not, you have to ask yourself: What would be the benefits of vaccinating children?, she told Italian newspaper La Repubblica in July.

We are not going to eradicate Sars-Cov-2. Its going to continue to circulate. And at some point, schools will remain open when there are infected children because, ultimately, we have to move to the point where we are living with the virus.

Dame Sarah first read about a novel virus spreading through the Chinese city of Wuhan on New Years Day 2020. She had designed a vaccine for it within two weeks, which was granted approval for use just 351 days later, one day before the year was out. Her own triplets, all studying biochemistry at university now, took part in the human trial.

A few stuttering months of confusion prior to the European Medicines Agency (EMA) declaring the overall benefits of Dame Sarah's vaccine outweighed the risks of one particular complication (developing a rare blood clot), with the risk of the rare clot from the vaccine eight times less than the risk of a clot caused by Covid-19, according to an Oxford University study Boris Johnson, Sir Keir Starmer, the Duke and Duchess of Cambridge and Dame Joan Collins included.

How frustrating it has been, then, for Dame Sarah who has since been lauded around the world, showered in medals and awards, had a Scientist Barbie designed after her, and even invited to sashay on to certain celebrity shows, of which more later to have been forced to spend the past year making clear that the vaccine is definitely safe, not having been chucked together in a lab at top speed like a cake made the night before the village fte.

Indeed, she and Dr Cath Green, associate professor in chromosome dynamics at the Wellcome Centre for Human Genetics at the University of Oxford and part of Dame Sarahs vaccine development team, have also taken the time to write Vaxxers (Hodder & Stoughton, 20), which explains clearly and in a very readable way how carefully and precisely the vaccine was developed.

We wanted to explain how we did this so fast, Dame Sarah explains. We appreciate it is natural for people to be hesitant.

But, in a nutshell, the vaccine came down to two things: advances in technology and development, combined with the reality of working in a pandemic: there was none of the normal hold-ups to slow down the team.

We were able to overlap processes that you would normally do sequentially, she says. We had less waiting to do between elements of work. But we still followed the normal regulatory pathway. Yes, we did it quickly, but we didnt miss any steps out. It is frustrating when people say development was too fast without saying why that would be.

Key to this was some unlikely help that came early on. At the start of January 2020, before the pandemic had been declared, Chinese scientists from Fudan University in Shanghai posted the fully sequenced genetic code for the new virus to enable the worlds scientists to move fast.

Vaccinologists, she says, are a close community. Weve always known that beating Covid was not winner takes all. There was no competition to come first. We need vaccines for everyone in the world.

This business-like approach is connected to Dame Sarahs biotech company Vaccitech, which she set up in 2016. Im a scientist to my core, she says, but Ive always wanted my science to make things better for people. Products can be developed better by a company than a university.

Vaccitech is already moving on, looking at way its vaccines could work in other conditions such as hepatitis B and prostate cancer. Thats the dream to have a targeted cancer treatment.

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Dame Sarah Gilbert: 'We don't need to give vaccine boosters to everybody. Immunity is lasting well' - Telegraph.co.uk