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Scientists Create the most Accurate Epigenetic Clock Yet

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If you are curious about how you age and whether you are naturally prone to develop certain diseases, then you probably want to pay more attention to the Epigenetic clock.

Scientists have developed the epigenetic clock which reveals information on the connection between a rapidly ageing brain and Dementia, including Alzheimer’s disease.

The epigenetic clock is to ageing what the circadian clock is to sleeping and waking cycles.

The scientists who are based at the University of Exeter analyzed brain tissue samples taken from human brains to come up with the epigenetic clock. The epigenetic clock is more accurate than others created using other tissue samples or blood samples.

According to lead researcher Professor Jonathan Mill, more research into Epigenetic clocks could unlock more understanding of the aging process.

“Our new clock will help us explore accelerated aging in the human brain. As we’re using brain samples, this isn’t a model that can be used in living people to tell how fast they’ll age. However, we can apply it to donated brain tissue to help us learn more about the factors involved in brain diseases such as dementia” says Mill.

Researchers studied the epigenetic markers responsible for DNA methylation within the human cortex. These epigenetic markers signal genes to switch on or go off.

The result is the most accurate epigenetic clock so far – one that predicts the biological age of the brain more accurately than ever before, according to Gemma Shireby of the University of Exeter.

The scientists eventually found 347 DNA methylation sites and it through these sites that they were able to make their accurate predictions within the cortex.

Their model held up when it was tested against 1,221 brain tissue samples collected by the Brains for Dementia Research cohort. The BRD cohort gets is funding from the Alzheimer’s Research UK and the Alzheimer’s Society on 1,175 blood samples.

The methylation data was instrumental in the creation of biomarkers for aging. These biomarkers for ageing are epigenetic clocks.

These clocks help scientists to understand how biological age and chronological change differ in terms of managing diseases like neurodegeneration as well as dementia among other brain types.

Researchers are excited because the new epigenetic body clock beats all its predecessors in its predictions of the biological age of the human brain.

They conclude that the reason why this new epigenetic clock is so accurate is that they used brain tissue samples relevant to the study of brain health. Because they were working with brain tissue, they were able to come up with a more accurately calibrated epigenetic clock to enable them to investigate dementia.

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IVF gets Better with AI

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An Israeli startup has found a way to make fertility treatments more successful using Artificial Intelligence.

Embryonics has already seen no less than 6 full term pregnancies as a result of their novel system.

Doctors will often inseminate a female egg in a laboratory – a process known as In Vitro Fertilization. During first few days after the fertilization, the embryos will be housed in special incubators and watched continuously by an embryologist.

This embryologist will then return some of the embryos for in-human incubation. This is where it gets interesting because they have to choose what they feel are the most valuable embryos.

“The decision making is subjective, and is dependent on experience and intuition – a factor that changes between doctors and medical centers. Embryonics wide range of smart solutions simplifies complex processes with data-backed insight, aiming at optimizing quality and fertilizations rate success,” says Embryonics founder and CEO Yael Gold-Zamir.

The company says that the success rate of traditional methods of IVF carries a 30% success rate within the US, and that the success rate is even lower outside the US.

The company developed AI algorithms that help predict the likely success rate of fertility and IVF treatments. This takes a lot of the guesswork out of the selection process.

To train the model, scientists watched embryos developing during IVF treatment. As a result, the embryo-pregnancy success rate shot up by 20% and the model allowed doctors to predict the embryos that would not yield a successful pregnancy.

This difference is significant because it saves IVF patients a significant amount of money by making the process more efficient. By increasing the chances of success, it also saves patients from the emotional toll of unsuccessful IVF attempts.

Test Tube Babies become AI Babies

According to Dr. Gold-Zamir, Embryonics has come up with Ubar, the first commercially viable product that more accurately pinpoints healthy embryos.

It won’t be long before Embryonics’ product is in the market: The product could be CE cleared in a matter of weeks, and FDA approved within the year.

“Once regulatory approvals are in, we will start implementing the product in a number of Israeli medical centers that showed interest.”

“It’s a revolution. Traditional fertility treatments resulted in very low success rate. We are going to replace IVF test-tube babies with AI babies – a transition that will create a process that is shorter, cheaper, and less dangerous for millions of couples around the world.” Adds Zamir.

If we go by the findings of Israeli startups like Embryonics, AIDOC, and Zebra, you may be forgiven for thinking that AI medical imaging analysis may replace specialist like radiologists and embryologists in the near future.

But Dr. Gold-Zamir differs: “Algorithms will take over some of the radiologist’s tasks, opening more time for physicians to take a deeper dice into patient care. But that’s further down the road. Currently, all the available tools aid and improve radiologist and doctors’ workflow and quality, with tools trained in millions of different sample sources – a database too large for humans to process.”

The effect of Artificial Intelligence it appears, will be to make medical experts more accurate in their diagnoses, and not to replace them.

Dr. Yael Gold-Zamir founded Embryonics in 2018 and the company has grown to its current composition of 16 people. Embryonics has raised a $4million round of funding with the Schuctermann Family Investment Office as well as the Israel Innovation Authority.

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Four-Week Memory Test that could predict the Risk of Alzheimer’s

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Scientists now believe that it may be possible to identify people who have a greater risk of developing Alzheimer’s disease by testing their memory over a four-week period.

Trials have shown that zeroing in on the ability to retain a memory over a longer period could yield potentially more accurate predictors than the traditional memory tests. Traditional memory tests assess people’s memory over a period of half an hour.

University of Bristol researchers led the study which they published in the Alzheimer’s Research and Therapy journal in which they wanted to test using a word list to test people’s memory over four weeks. People were tested for their memory of the list four weeks after hearing it initially.

Those whose memory of the list after four weeks was better off, registered less cognitive decline over the year after. This was true even for those who did not have any problems with cognitive function or memory at the start.

Forty six older people participated in the study. All of them were healthy and their average age was 70.7. The study participants had to perform three memory tasks. Researchers tested t heir delayed recall 30 minutes later and then four weeks later.

They also did the Addenbrooke’s Cognitive Examination III or ACE-III test. ACE-III test is conventionally used to detect cognitive impairments, as well as a brain MRI. One year later, the participants repeated the same ACE-III test to measure their cognitive abilities.

At the end of the study, researchers found that 15 out of 46 participants had experienced a decline in their cognitive abilities, and that the verbal memory tests conducted over the initial period of four weeks would have yielded a better prediction of this decline than the standard memory tests.

After combining the scores from the four-week memory tests together with the results of the MRI brain scan, the researchers found that it was possible to make even more accurate prediction s of cognitive decline.

The MRI brain scans showed that there was a size reduction in the section of the brain that governs memory. This is the part of the brain that gets affected by Alzheimer’s Disease.

By testing long-term memory recall, the researchers found that they could detect Alzheimer’s disease much earlier and achieve better treatment outcomes. Treatments to stop Alzheimer’s disease or slow down its progression are much more effective when given during the early stages of the disease. This is the best time because patients are yet to develop significant problems with their memory.

In the words of Dr. Alfie Wearn, a Research Associate at the Bristol Medical School: Translational Health Sciences: “Our study shows evidence for a low-cost and quick to administer screening tool that could be used to identify the very earliest signs of Alzheimer’s disease. It could also directly speed up the development of effective Alzheimer’s disease therapies, and enable earlier treatment when such therapies are available.”

Dr. Liz Coulthard who is an Associate Professor in Dementia Neurology with the University of Bristol as well as a neurologist with the North Bristol NHS Trust also said this: “It is important to note the participants were healthy older people who did not develop Alzheimer’s during the trial, but some people did show the type of change over the course of a year in memory and thinking that can precede Alzheimer’s disease. Future work will establish whether this test predicts full-blown Alzheimer’s dementia.”

Researchers will now be testing the ability of these tests to detect Alzheimer’s disease in comparison with other cognitive deteriorating diseases. The researchers will be drawing comparisons between long-term memory test results of people who have evidence of Alzheimer’s disease and those without. The evidence is derived from analyzing their cerebrospinal fluid. Even though this method of detecting Alzheimer’s is the most effective, it is also too invasive, and researchers are working on less invasive methods.

The study was conducted with funding from a Wellcome Trust PhD study scholarship award received by Dr. Wearn who is in the Neural Dynamics PhD Programme. It was also funded by the Alzheimer’s Research UK as well as Brace, which is a dementia charity at Southmead Hospital in Bristol.

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An ionic forcefield for nanoparticles

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Nanoparticles may have the solution to awful side effects from chemotherapy. If doctors can use nanoparticles to carry drugs directly to a specific part of the body, they can make chemotherapautics less toxic.

But it is not that simple. Because nanoparticles trigger the body’s immune system to fight against them, the vast majority of them never reach their target.

Human blood serum contains proteins that tag the nanoparticles as invadors and a paltry 1% of the nanoparticles get to where they are going.

“No one escapes the wrath of the serum proteins,” said Eden Tanner, who was a postdoctoral Bioengeneering fellow at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

A research team led by Tanner and Professor Samir Mitragotri have created an ionic forcefield that could enable nanoparticles to achieve their goal by preventing the proteins in the blood serum from tagging the nanoparticles.

In experimenting with mice, the researchers found that the could make the nanoparticles to survive longer in the human body using a coat of the ionic liquid. This coating increased the number of nanoparticles that reached their target from 1% to more than 50%.

“The fact that this coating allows the nanoparticles to slip past serum proteins and hitch a ride on red blood cells is really quite amazing because once you are able to fight the immune system effectively, lots of opportunities open up,” explained Mitragotri, who is part of the Harvard’s Wyss Institute for Biologically Inspired Engineering faculty.

Ionic liquids are liquid salts and they are capable of holding charge.

“We knew that serum proteins clear out nanoparticles in the bloodstream by attaching to the surface of the particle and we knew that certain ionic liquids can either stabilize or destabilize proteins,” said Tanner, an assistant professor of chemistry and biochemistry at the University of Mississippi. “The question was, could we leverage the properties of ionic liquids to allow nanoparticles to slip past proteins unseen.”

The great thing about ionic liquids is that every small change you make to their chemistry results in a big change in their properties,” explained Christine Hamadani, who was the first author and a former graduate student at SEAS. “By changing one carbon bond, you can change whether or not it attracts or repels proteins.”

At the moment, Hamadani is a graduate student based at Tanner’s lab in the University of Mississippi.

Researchers used choline hexenoate to coat the nanoparticles. It is an ionic liquid with a natural aversion to serum proteins. The nanoparticles coated with ionic liquid attached themselves to red-blood cells and remained in circulation until they got to the lungs.

“This hitchhiking phenomenon was a really unexpected discovery,” said Mitragotri. “Previous methods of hitchhiking required special treatment for the nanoparticles to attach to red blood cells and even then, they only stayed at a target location for about six hours. Here, we showed 50 percent of the injected dose still in the lungs after 24 hours.”

The scientists are yet to understand exactly why the nanoparticles so easily attached themselves to lung tissue, but it shows that the system can work with a fair amount of precision.

“This is such a modular technology,” said Tanner, who plans will go on with her research at University of Mississippi. “Any nanoparticle with a surface change can be coated with ionic liquids and there are millions of ionic liquids that can be tuned to have different properties. You could tune the nanoparticle and the liquid to target specific locations in the body.”

“We as a field need as many tools as we can to fight the immune system and get drugs where they need to go,” said Mitragotri. “Ionic liquids are the latest tool on that front.”

Morgan J. Goetz co-authored the research paper.

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