Culture

Philadelphia, July 24, 2020--Researchers at Children's Hospital of Philadelphia (CHOP) have developed a new computational algorithm that has, for the first time, identified a spectrum of mutations in the noncoding portion of the human genome across five major pediatric cancers. The study, which was published today in Science Advances, used the algorithm to analyze more than 500 pediatric cancer patients' mutations and gene expression profiles to develop a comprehensive list of potentially cancer-causing mutations.

"Noncoding mutations are very important because the noncoding portion of the genome typically regulates how genes are turned on and off, much like a control switch, which has implications for the uncontrolled growth that occurs in cancer," said Kai Tan, PhD, Professor of Pediatrics at CHOP and senior author of the study. "However, these regions are also challenging to study, and our knowledge about them not as developed as that of coding regions. Our computational model has identified a set of targets in pediatric cancers that we hope to study further and eventually move to clinical practice."

The researchers developed a computation tool called PANGEA (predictive analysis of noncoding genomic enhancer/promoter alterations) to analyze noncoding mutations and their impact on gene expression in more than 500 pediatric cancer patients who had five major types of pediatric cancer: B cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML), neuroblastoma, Wilms tumor, and osteosarcoma. PANGEA identified all types of mutations that are associated with gene expression changes, including single nucleotide variants, small indels, copy number variations, and structural variants.

Previous studies on noncoding mutations have focused on single nucleotide variants and small indels, which are insertions or deletions of bases in the genome that are relatively short in length. However, structural variants are regions of DNA much larger in size - 1 kilobase or larger - a quality that makes them more difficult to identify but also more likely to contribute to changes in gene regulation that lead to cancer.

Using PANGEA, the researchers found that structural variants are indeed the most frequent cause of potentially cancer-causing mutations and identified 1,137 structural variants that affect the expression of more than 2,000 genes across the five pediatric cancer types.

In analyzing the data, the researchers found that coding and noncoding mutations affect distinct sets of genes and pathways, which is likely due to the different genomic locations of these two types of genes. The researchers found that genes involved in metabolism - the rewiring of which is a hallmark of cancer - are more frequently affected by noncoding mutations. However, it is unclear to what degree noncoding mutations facilitate metabolism rewiring in the five cancer types the researchers studied.

"Our results highlight the need for comparative analysis of both coding and noncoding mutations, which might reveal novel cancer-related genes and pathways," said Tan. "Identifying putative mutations is a starting point that will facilitate experimental work to validates these predictions."

MEDFORD/SOMERVILLE, Mass. (July 24, 2020) --Biomedical engineers at the Tufts University School of Engineering have developed tiny lipid-based nanoparticles that incorporate neurotranmitters to help carry drugs, large molecules, and even gene editing proteins across the blood-brain barrier and into the brain in mice. The innovation, published today in Science Advances, could overcome many of the current limitations encountered in delivering therapeutics into the central nervous system, and opens up the possibility of using a wide range of therapeutics that would otherwise not have access to the brain.

"The power of our method is that it is extremely versatile and relatively non-disruptive," said Qiaobing Xu, associate professor of biomedical engineering at Tufts University and corresponding author of the study. "We can deliver a wide range of molecules by packaging them into the lipid-based nanonparticles without chemically modifying the drugs themselves. We can also achieve delivery across the blood-brain barrier without disrupting the integrity of the barrier."

Xu cautioned that more studies and clinical trials are needed to determine the efficacy and safety of the delivery method in humans.

The blood-brain barrier consists of a layer of endothelial cells that line the blood vessels in the brain and allows only a highly select set of molecules to pass from the bloodstream into the fluid surrounding the neurons and other cells of the brain.The ability to safely and efficiently deliver therapeutic molecular cargos across the barrier and into the brain has been a long-standing challenge in medicine.

The treatment of neurodegenerative disorders, brain tumors, brain infections and stroke has been limited by the difficulty in safely delivering small molecule drugs and macromolecules, such as peptides and proteins, into the brain. Current approaches, such as direct injection or disruption of the barrier to make it "leaky," are fraught with risks, including infection, tissue damage and neurotoxicity. The use of carriers, such as modified viruses and monoclonal antibodies to ferry cargo into the brain, has limitations, including production cost and safety. Other carriers, such as nanoparticles, nanocapsules and polymers, have shown promise but the modifications required to ensure delivery can be complicated.

The study authors made use of the fact that certain neurotransmitters have the chemical "passport" required to gain access throughout the brain. By attaching a lipid (fat-like) molecule to the neurotransmitter, the resulting NT-lipidoid can be doped into lipid nanoparticles (LNPs) - tiny bubbles of lipid that can encapsulate other molecules within, in particular therapeutic drugs. The LNPs can be injected intravenously, and carry the drugs to the blood-brain barrier, while the NT-lipidoid helps the LNPs to carry the drugs across the barrier. The LNPs can then fuse with neurons and other cells in the brain to deliver their therapeutic payload.

Using the LNPs with NT-lipidoid, the researchers successfully delivered into the brain of a mouse:

a small molecule antifungal drug, amphotericin B;

macromolecules including a Tau antisense oligonucleotide, which inhibits the production of tau protein connected to Alzheimer's disease; and

the gene editing protein GFP-Cre.

The researchers observed the effect of diminished tau protein, as well as direct evidence of the gene editing protein entering neurons. In fact, the latter was the first demonstration of genome editing within neurons delivered via intravenous injection, according to the researchers.

While more studies and clinical trials are needed, the delivery method could be a significant advance in convenience and a general application for central nervous system drug delivery. The Tufts researchers found that the addition of the NT-lipidoid to many varieties of LNPs can render them permeable to the blood-brain barrier. That means that LNPs can be optimized for lipid length and ratios to package drugs of different types, from small molecules to DNA to large enzyme complexes, and then provided the same blood-brain barrier permeability by addition of the NT-lipidoid.

"It's simple, effective, and potentially broadly applicable - we can modify the container for the drug, and by adding the NT-lipidoid, it's like attaching an address label for delivery into the brain," said Feihe Ma, post-doctoral scholar in the Xu lab at Tufts. "We envision that a wide range of neurological therapeutics could eventually be tried that were previously thought to be impractical due to limitations in delivery," said Liu Yang, graduate student in the Xu lab. Ma and Yang are co-first authors of the study.

What The Study Did: The use of medical leave among emergency medical service responders and firefighters in New York during the COVID-19 pandemic is compared with earlier periods.

Authors: David J. Prezant, M.D., of the Bureau of Health Services and the FDNY World Trade Center Health Program of the Fire Department of the City of New York, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.16094)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

Most meteorites that have landed on Earth are fragments of planetesimals, the very earliest protoplanetary bodies in the solar system. Scientists have thought that these primordial bodies either completely melted early in their history or remained as piles of unmelted rubble.

But a family of meteorites has befuddled researchers since its discovery in the 1960s. The diverse fragments, found all over the world, seem to have broken off from the same primordial body, and yet the makeup of these meteorites indicates that their parent must have been a puzzling chimera that was both melted and unmelted.

Now researchers at MIT and elsewhere have determined that the parent body of these rare meteorites was indeed a multilayered, differentiated object that likely had a liquid metallic core. This core was substantial enough to generate a magnetic field that may have been as strong as Earth's magnetic field is today.

Their results, published in the journal Science Advances, suggest that the diversity of the earliest objects in the solar system may have been more complex than scientists had assumed.

"This is one example of a planetesimal that must have had melted and unmelted layers. It encourages searches for more evidence of composite planetary structures," says lead author Clara Maurel, a graduate student in MIT's Department of Earth, Atmospheric, and Planetary Sciences (EAPS). "Understanding the full spectrum of structures, from nonmelted to fully melted, is key to deciphering how planetesimals formed in the early solar system."

Maurel's co-authors include EAPS professor Benjamin Weiss, along with collaborators at Oxford University, Cambridge University, the University of Chicago, Lawrence Berkeley National Laboratory, and the Southwest Research Institute.

Oddball irons

The solar system formed around 4.5 billion years ago as a swirl of super-hot gas and dust. As this disk gradually cooled, bits of matter collided and merged to form progressively larger bodies, such as planetesimals.

The majority of meteorites that have fallen to Earth have compositions that suggest they came from such early planetesimals that were either of two types: melted, and unmelted. Both types of objects, scientists believe, would have formed relatively quickly, in less than a few million years, early in the solar system's evolution.

If a planetesimal formed in the first 1.5 million years of the solar system, short-lived radiogenic elements could have melted the body entirely due to the heat released by their decay. Unmelted planetesimals could have formed later, when their material had lower quantities of radiogenic elements, insufficient for melting.

There has been little evidence in the meteorite record of intermediate objects with both melted and unmelted compositions, except for a rare family of meteorites called IIE irons.

"These IIE irons are oddball meteorites," Weiss says. "They show both evidence of being from primordial objects that never melted, and also evidence for coming from a body that's completely or at least substantially melted. We haven't known where to put them, and that's what made us zero in on them."

Magnetic pockets

Scientists have previously found that both melted and unmelted IIE meteorites originated from the same ancient planetesimal, which likely had a solid crust overlying a liquid mantle, like Earth. Maurel and her colleagues wondered whether the planetesimal also may have harbored a metallic, melted core.

"Did this object melt enough that material sank to the center and formed a metallic core like that of the Earth?" Maurel says. "That was the missing piece to the story of these meteorites."

The team reasoned that if the planetesimal did host a metallic core, it could very well have generated a magnetic field, similar to the way Earth's churning liquid core produces a magnetic field. Such an ancient field could have caused minerals in the planetesimal to point in the direction of the field, like a needle in a compass. Certain minerals could have kept this alignment over billions of years.

Maurel and her colleagues wondered whether they might find such minerals in samples of IIE meteorites that had crashed to Earth. They obtained two meteorites, which they analyzed for a type of iron-nickel mineral known for its exceptional magnetism-recording properties.

The team analyzed the samples using the Lawrence Berkeley National Laboratory's
Advanced Light Source, which produces X-rays that interact with mineral grains at the nanometer scale, in a way that can reveal the minerals' magnetic direction.

Sure enough, the electrons within a number of grains were aligned in a similar direction -- evidence that the parent body generated a magnetic field, possibly up to several tens of microtesla, which is about the strength of Earth's magnetic field. After ruling out less plausible sources, the team concluded that the magnetic field was most likely produced by a liquid metallic core. To generate such a field, they estimate the core must have been at least several tens of kilometers wide.

Such complex planetesimals with mixed composition (both melted, in the form of a liquid core and mantle, and unmelted in the form of a solid crust), Maurel says, would likely have taken over several million years to form -- a formation period that is longer than what scientists had assumed until recently.

But where within the parent body did the meteorites come from? If the magnetic field was generated by the parent body's core, this would mean that the fragments that ultimately fell to Earth could not have come from the core itself. That's because a liquid core only generates a magnetic field while still churning and hot. Any minerals that would have recorded the ancient field must have done so outside the core, before the core itself completely cooled.

Working with collaborators at the University of Chicago, the team ran high-velocity simulations of various formation scenarios for these meteorites. They showed that it was possible for a body with a liquid core to collide with another object, and for that impact to dislodge material from the core. That material would then migrate to pockets close to the surface where the meteorites originated.

"As the body cools, the meteorites in these pockets will imprint this magnetic field in their minerals. At some point, the magnetic field will decay, but the imprint will remain," Maurel says. "Later on, this body is going to undergo a lot of other collisions until the ultimate collisions that will place these meteorites on Earth's trajectory."

Was such a complex planetesimal an outlier in the early solar system, or one of many such differentiated objects? The answer, Weiss says, may lie in the asteroid belt, a region populated with primordial remnants.

"Most bodies in the asteroid belt appear unmelted on their surface," Weiss says. "If we're eventually able to see inside asteroids, we might test this idea. Maybe some asteroids are melted inside, and bodies like this planetesimal are actually common."

People are very skilled with their hands, but take a very long time to learn various dexterous abilities. It takes babies generally around five months before they can purposely grip an object. Learning more complicated skills such as eating with fork and knife or tying one's shoelaces can take another five to six years. By that age, many other primate species already have offspring of their own. Why do we take so much longer than our closest relatives to learn fine motor skills?

Brain development in primates follows fixed patterns

Sandra Heldstab, an evolutionary biologist in the Department of Anthropology at the University of Zurich, and her colleagues Karin Isler, Caroline Schuppli and Carel van Schaik observed 36 different primate species over a period of more than seven years to try to answer this question. She studied 128 young animals in 13 European zoos from birth until the age at which they had reached adult-level dexterity. What surprised her was that all species learned their respective manual skills in exactly the same order. "Our results show that the neural development follows extremely rigid patterns - even in primate species that differ greatly in other respects," says Heldstab.

Large brain needed for dexterity

The researchers found, however, big differences in the specific fine motor skills of adults from different primate species. Large-brained species such as macaques, gorillas or chimpanzees can solve much more complex tasks using their hands than primates with small brains such as lemurs or marmosets. "It is no coincidence that we humans are so good at using our hands and using tools, our large brains made it possible. A big brain equals great dexterity," says Heldstab.

Humans develop fine motor skills later than primates

Dexterity comes at a cost, however: In species with large brains like humans, it takes a long time for infants to learn even the simplest hand and finger movements. "It's not just because we are learning more complex skills than lemurs or callitrichids, for example. It's mainly because we do not begin learning these skills until much later," says Heldstab. The researchers think that the reason for this may be that the larger brains of humans are less well developed at birth.

Essential to have enough time to learn

In addition, learning takes time and is inefficient, and it is the parents who pay for this until their offspring are independent. "Our study shows once again that in the course of evolution, only mammals that live a long time and have enough time to learn were able to develop a large brain and complex fine motor skills including the ability to use tools. This makes it clear why so few species could follow our path and why humans could become the most technologically accomplished organism on this planet," concludes Sandra Heldstab.

Patients with frailty, older age and urinary tract infections (UTIs) are at greatest risk of developing sepsis following infection consultations in primary care, research has found.

A research study published today in PLOS Medicine by researchers from King's College London, with funding from National Institute for Health Research (NIHR), aimed to estimate the probability of a patient developing sepsis following an infection consultation in primary care if they were or were not prescribed antibiotics.

Sepsis is a severe reaction to an infection that can lead to life threatening damage to organ systems. Without treatment, sepsis can lead to multiple organ failure and death. There are more than 200,000 hospital admissions for sepsis each year in England and up to 59,000 deaths.

Antibiotic therapy may reduce the risk of sepsis, however unnecessary antibiotic prescribing is a major concern in primary care which may be contributing to the development of antimicrobial resistance.

Researchers analysed all registered patients at 706 general practices in the UK, with 66.2million person years of follow-up from 2002 to 2017. The cohort included 35,244 first episodes of sepsis, of which 51% were female, with a median age of 71 years.

The study aimed to estimate the probability of a patient developing sepsis following an infection consultation in primary care, if antibiotics are or are not prescribed, and to estimate the number of antibiotic prescriptions required to prevent one episode of sepsis.

The risk of sepsis following an infection consultation in primary care increased with age, and the number of antibiotic prescriptions required to prevent one sepsis event decreased with age.

Frailty level was also associated with greater risk of sepsis. Patients at age 55 years with severe frailty have similar probability of sepsis as a non-frail 85-year-old.
At all ages, the probability of sepsis was greatest for urinary tract infection, followed by skin infection, and then by respiratory tract infection.

The authors concluded antibiotic prescriptions may be safely more reduced in groups with lower probability of sepsis.
Professor Martin Gulliford from King's College London said: "This research helps to identify groups of patients in which antibiotic prescribing may be more safely reduced. Risks of sepsis, and benefits of antibiotics, are more substantial among older adults, patients with more advanced frailty or following UTIs."

Jo Rycroft-Malone, NIHR Programme Director and Chair of the Health Services and Delivery Research (HS&DR) Programme said: "Reducing the use of antibiotics and tackling antimicrobial resistance remain research priorities for the NIHR. The results of this study are valuable for the practice of antibiotic prescribing looking forward as they indicate where practitioners may be able to safely reduce their use."

BATON ROUGE, Louisiana - A hormone that connects the body's metabolism and immune response system may explain why COVID-19 is so dangerous for people with obesity.

"The problem for people with obesity is that their leptin levels are always high, and that can affect the response to a COVID-19 infection," said Candida Rebello, PhD, RD, lead author of a new paper that traces the link between obesity and the virus.

The hormone leptin regulates appetite and metabolism. Leptin also regulates the cells that fight infection. Leptin is produced by fat cells, and to a lesser extent by tissues in the lungs. The more fat a person has, the more leptin circulates in their body.

Elevated leptin levels hamper the body's ability to fight off infections, in the lungs and elsewhere, Dr. Rebello said. High leptin levels promote a low-grade systemic inflammatory state.

"If you have obesity, there are a number of underlying health issues that make it more difficult for you to fight off a COVID-19 infection," said John Kirwan, PhD, Pennington Biomedical Executive Director and a co-author of the review. "Your entire body, including your lungs, may be inflamed. Your immune response is likely compromised, and your lung capacity reduced.

"Add in a virus that further weakens the body's ability to fight infection, that can limit the body's ability to control lung inflammation, and you have the recipe for disaster."

COVID-19 vaccine developers should take the immunocompromised state resulting from obesity into consideration, in much the same way they would advancing age.

The researchers say the role of leptin in COVID-19's development bears investigation along with the viral proteins that alter the immune systems of people with obesity. One potential avenue of treatment may be a drug that prevents inflammatory responses to the virus.

Another potential avenue of investigation includes examining how proinflammatory fat tissue in people with obesity might contribute to activating fewer infection-fighting cells and why those cells die more quickly.

COLUMBUS, Ohio - Research conducted at The Ohio State University Wexner Medical Center and The Ohio State University College of Medicine found that spinal cord injuries in mice cause an acquired bone marrow failure syndrome that may contribute to chronic immune dysfunction.

"We also found that it's possible to overcome certain aspects of spinal cord injury-induced bone marrow failure. This could have an immediate impact on people affected by spinal cord injury," said lead author Phillip Popovich, chair of the Ohio State Department of Neuroscience and executive director of Ohio State's Belford Center for Spinal Cord Injury and Center for Brain and Spinal Cord Repair.

Findings are published online in the journal Nature Communications.

Spinal cord injury (SCI) is known to cause immune system dysfunction, which increases the risk of infections. This, in turn, increases hospitalizations and premature death.

Immune cells are made in the bone marrow. Healthy bone marrow requires proper communication with the nervous system, notably the spinal cord.

"Our research shows that spinal cord injury causes stem cells in the bone marrow - those required to make new immune cells - to rapidly divide. But after cell division, these cells become trapped in the bone marrow. We discovered one possible explanation for this," said Randall S. Carpenter, first author and recently graduated PhD student from Ohio State's Neuroscience Graduate program.

Notably, in bone marrow of mice with spinal cord injuries, there's an increase in chemical signaling between stem progenitor cells and support cells in the bone marrow. This enhanced signaling locks the cells down so they can't move away from the "niches" in which they are born and develop.

This lockdown can be reversed by post-injury injections of the FDA-approved drug Plerixafor, a small molecule inhibitor of CXCR4, a chemokine receptor. Even though Plerixafor frees blood stem cells and mature immune cells from bone marrow, other techniques showed that the intrinsic long-term functional capacity of bone marrow stem/progenitor cells is still impaired for several months post-injury.

Bone marrow failure diseases develop when the bone marrow can't produce enough healthy mature white and red blood cells. Normal aging and various diseases including diabetes, cancers and chemotherapy also trap mature and immature cells in the bone marrow.

"In spinal cord injury patients, Plerixafor could be a potentially safe and effective way to mobilize cells from the bone marrow niche to help restore immune function. In fact, Plerixafor is already used in other clinical indications to help reverse immunodeficiency in patients; it just hasn't been used after spinal cord injury," Popovich said. "While this study was done in mice, these new data help explain observations that have been made in humans with spinal cord injuries," Popovich said. "More research is needed to understand why the bone marrow failure develops, and whether it's permanent."

Curtin University researchers have unexpectedly discovered a new way to make crystalline graphite, an essential material used in the making of lithium ion batteries.

Described in a research paper published today in Nature's Communications Materials, the new technique does not require the typical metal catalysts or special raw materials to turn carbon into crystalline graphite. Interestingly it was instead discovered by a research student in a lab, using an Atomic Absorption Spectrometer (AAS) - a piece of equipment, invented in Australia in the 1950s and developed to analyse the composition of liquids.

The Master-level student behind the discovery, Mr Jason Fogg, said that while the exact science behind why this new technique works is still to be confirmed, he believes it relates to the specific way the AAS heats the samples through short fast pulses.

"We used a special furnace that can heat the sample to 3000 degrees Celsius in seconds, something most furnaces cannot achieve," Mr Fogg said.

"To put the temperature into perspective, 3000 degrees Celsius is equal to about half the surface temperature of the Sun."

Dr Irene Suarez-Martinez, from Curtin's School of Electrical Engineering, Computing and Mathematical Sciences, said that while graphite is the most stable form of carbon, most carbon materials stubbornly refuse to turn into graphite, which is why she was absolutely shocked to learn about Mr Fogg's results.

"When he told me that he created perfect crystalline graphite from a known non-graphitising carbon material, I could not believe it, I was absolutely amazed at the results. It was only when we repeated the results three times that I was convinced," Dr Suarez-Martinez said.

The most astonishing result involved the polymer polyvinylidene chloride (PVDC), which Dr Suarez-Martinez described as a 'textbook example' of a very stubborn material.

As the world's demand for lithium ion batteries increases, scientists expect the commercial demand for crystalline graphite to also increase, and this research team is now determined to work out the precise details of why this special pulse heating method was so effective.

"Our hypothesis is that atmospheric oxygen soaks into the structure between pulses, and the rapid heating on the next pulses burns away the structures that would usually prevent graphite from forming," Dr Suarez-Martinez said.

"We're also interested to see if other complex carbons will also transform. Could this method be able to convert organic carbon material, such as food waste, into crystalline graphite?

"Right now we're only able to create very small amounts of crystalline graphite, so we are far from being able to reproduce this process on a commercial-level. But we plan to explore our method and hypotheses further."

Research has shown a global increase in the emergence of infectious diseases and epidemics, an accelerated loss of biodiversity and a marked increase in the breeding of domesticated animals. This subject was brought back to the fore by the COVID-19 outbreak and a new study in parasite ecology is providing some initial answers to the ongoing question of whether these events are connected. Its goal was to trace the global patterns of biodiversity and infectious diseases both spatially and temporally.

To achieve this, the researcher cross referenced various open databases* on human and animal health, livestock expansion and biodiversity loss. An initial analysis showed that the number of epidemics identified in humans in each country increased in correlation with local biodiversity loss (16,994 epidemics caused by 254 infectious diseases between 1960-2019). The emergence of epidemics is a worrying sign for the future of species conservation as it could well signal biodiversity's march towards extinction. The relation between the number of endangered species and the number of epidemics first increases, then peaks, before finally declining. However, the risk of an epidemic does not decrease with the disappearance of a species, but on the contrary, is further relayed by the growing number of head of cattle. Data from 2006-2019 confirms this second result placing it at the heart of a potential health risk. Livestock expansion worldwide directly affects wildlife as well as the incidence of epidemics in humans and in domesticated animals.

The study brings up the question of the place of farmed animals and their increase across the world, which varies according to factors such as human demographics and diet. In order to lower the health risk and protect biodiversity we need to take into account the cultural value of animals to reflect on the place of both wild and domesticated species. Future studies will examine the role played by livestock in pandemics by looking at, on the one hand, the cultivation of vegetable protein needed for feed, which contributes to reduce the space for wild animals, and on the other, on the role of livestock as an epidemiological bridge between wildlife and humans facilitating the transmission of pathogens.

If the eyes are the mirror of the soul, then thanks to the translucent corneas, we can look deep into that soul. And thanks to the work of scientists from the IPC PAS we can look into the depths of the cornea itself. And that without touching it! All thanks to the introduction of an innovative method of holographic optical tomography.

"Our idea was to spoil the coherent laser beam illuminating the cornea, so we could significantly extend the exposure time without endangering the delicate retina. At the same time, it allows us to maintain a high value of light power, which allows us to see even a very weak light backscattered from the cornea," explains professor Wojtkowski. Additionally, the volumetric nature of the collected data allowed for the optical "flattening" of the cornea curvature and obtaining exceptionally sharp images of all its layers across the entire section. This is not an easy task, because the transparency of the cornea, although it allows to look inside the eye, does not facilitate the examination of the cornea itself.

The old methods required contact of the measuring device with the eye, and thus anaesthesia of the eyeball was mandatory, and the measurement itself - long-lasting. However, even the newer ones, using the OCT (optical coherence tomography), have limitations due to not fast enough image collection, which, when examining an unanaesthetized eye, makes the obtained image blurry due to micro-movement of the eyeball.

The breakthrough came with super-fast cameras recording tens of thousands of frames per second, which made it possible to record images at lightning speed. The problem in standard OCT was the resolution and artifacts resulting from the fact that the cornea is curved and scanning it, the laser beam is arranged slightly differently in each part. This is where the scientists from the IPC PAS come in. Their method, known as holographic OCT tomography, allows them to capture the cornea in a fraction of a second and to record its entire depth in an extremely high, unprecedented resolution. The patient will not even have time to blink, and his cornea is already imaged, with the accuracy so high that even single cells can be viewed. And if she or he even blinks (well, let's say moves the eye), the computer will compensate for this movement, still giving a sharp image.

- Moreover our new device has no moving parts, and thanks to the phase modulation of the laser beam we can use more power without harming deeper tissues of the eye," explains professor Wojtkowski.

The method developed by scientists from the International Centre for Translational Eye Research at the IPC PAS has a chance to revolutionize the diagnosis of eye diseases, not only corneas, giving doctors a tool to examine patients quickly and painlessly. Thanks to the fact that it also makes visible what is invisible in an ordinary slit lamp and is equally non-invasive, patients will gain comfort and ophthalmologists will gain incomparably more information.

According to a study published in Nature Biotechnology, the sVNT is capable of detecting the functional neutralising antibodies (NAbs) that can block the binding of the coronavirus spike protein to the angiotensin-converting enzyme 2 (ACE2) host receptor, which mimics the virus-host interaction.

The sVNT was developed by scientists from Duke-NUS Medical School, in close collaboration with National Centre for Infectious Diseases (NCID), Agency for Science, Technology and Research (A*STAR)'s Institute of Molecular and Cell Biology (IMCB) Singapore, and GenScript Biotech. The scientists in Singapore and China validated the test across two patient cohorts, with a sample size of 250 from China and 375 from Singapore, achieving 99-100 per cent specificity and 95-100 per cent sensitivity.

"The sVNT kit can detect functional NAbs in an hour and differentiate them with binding antibodies (BAbs), without the need for live virus or a biocontainment facility. It also has the ability to detect total receptor binding domain (RBD)-targeting neutralising antibodies in patient samples, in contrast to most SARS-CoV-2 antibody tests published or marketed, which are isotype-specific. This makes the sVNT accessible to the broader community for both research and clinical applications," said Professor Wang Linfa, Director of Duke-NUS' Emerging Infectious Diseases programme. Prof Wang is considered among the most recognised international experts on emerging zoonotic viruses and is currently serving on multiple WHO committees on COVID-19.

Infection or immunity to the virus is diagnosed by the presence of NAbs in a patient's blood sample, which would block the RBD-ACE2 interaction. At this critical moment of the international response to the COVID-19 outbreak, there is an urgent need for a robust serological test that detects NAbs, for accurate assessment of infection prevalence and protective immunity at the individual and population level. Antibody tests, such as the conventional virus neutralization test (cVNT) and the pseudovirus-based virus neutralization test (pVNT), remain the only platforms for detecting NAbs. However, both require live viruses and cells, highly skilled operators, and days to obtain results. Other assays, such as the enzyme-linked immunosorbent assay (ELISA) detect Babs but are unable to differentiate between BAbs and NAbs.

The sVNT can also measure NAbs from different animals in a species-independent manner. It can therefore be a powerful tool to investigate the role of animals in the transmission of COVID-19 from natural reservoirs to intermediate hosts.

"It is an increasingly critical clinical question about what proportion of patients with COVID-19 develop antibodies to COVID-19, how long it lasts, and whether antibodies protect patients from reinfection. Neutralising antibody is the gold-standard serological platform to determine this. Unfortunately, the conventional virus neutralisation assay is laborious, time-consuming and requires Biosafety Level 3 for COVID-19. The sVNT developed by Prof Wang, in collaboration with the national COVID-19 PROTECT study, makes it accessible to all hospital laboratories, and is a great advance in COVID-19 serological assays," said Associate Professor David Lye, Director, Infectious Disease Research and Training Office (IDRTO), and Senior Consultant, NCID.

Dr Sidney Yee, CEO of A*STAR's Diagnostics Development Hub, said, "Due to the SARS outbreak in 2003, researchers in Singapore have gained important insights into that virus, which shares some similarities with SARS-Cov-2. A*STAR supported the clinical tests in this collaboration with Duke-NUS by sharing data drawn from our research experience in SARS. We are happy to have contributed to the validation of this innovative test, which will be instrumental in our fight against the global pandemic."

"We are very pleased that Prof Wang's work has come to fruition," said Mr David Martz, Vice President of New Product Management, Life Sciences Group, at GenScript. "This is great news for scientists researching herd immunity and vaccine efficacy as they will now have access to this innovative research tool to accurately determine the level of neutralising antibodies in a population. We believe the test will shed new light on the current plaguing mysteries of COVID-19."

The sVNT kit is commercialised by GenScript and offered worldwide under the brand cPass™ for research use only. GenScript has also filed for Emergency Use Authorisation with the US Food and Drug Administration and this filing is currently under review.

Researchers at Lund University in Sweden have discovered a new method to treat human herpes viruses. The new broad-spectrum method targets physical properties in the genome of the virus rather than viral proteins, which have previously been targeted. The treatment consists of new molecules that penetrate the protein shell of the virus and prevent genes from leaving the virus to infect the cell. It does not lead to resistance and acts independently of mutations in the genome of the virus. The results are published in the journal PLOS Pathogenes.

Herpes virus infections are lifelong, with latency periods between recurring reactivations, making treatment difficult. The major challenge lies in the fact that all existing antiviral drugs to treat herpes viruses lead to rapid development of resistance in patients with compromised immune systems where the need for herpes treatment is the greatest (e.g. newborn children, patients with HIV, cancer or who have undergone organ transplantation).
Both the molecular and physical properties of a virus determine the course of infection. However, the physical properties have so far received little attention, according to researcher Alex Evilevitch.

"We have a new and unique approach to studying viruses based on their specific physical properties. Our discovery marks a breakthrough in the development of antiviral drugs as it does not target specific viral proteins that can rapidly mutate, causing the development of drug resistance - something that remains unresolved by current antiviral drugs against herpes and other viruses. We hope that our research will contribute to the fight against viral infections that have so far been incurable", says Alex Evilevitch, Associate Professor and senior lecturer at Lund University who, together with his research team, Virus Biophysics, has published the new findings.

The virus consists of a thin protein shell, a capsid, and inside it lies its genome, the genes. Alex Evilevitch has previously discovered that the herpes virus has high internal pressure because it is tightly packed with genetic material.

"The pressure is 20 atmospheres, which is four times higher than in a champagne bottle and this allows herpes viruses to infect a cell by ejecting its genes at high speed into the cell nucleus after the virus has entered the cell. The cell is then tricked into becoming a small virus factory that produces new viruses that can infect and kill other cells in the tissue, leading to different disease states", explains Alex Evilevitch.

He, with the help of preclinical studies at the National Institutes of Health in the United States, has identified small molecules that are able to penetrate the virus and "turn off" the pressure in the genome of the virus without damaging the cell. These molecules proved to have a strong antiviral effect that was several times higher than the standard treatment against certain herpes types with the drug Aciclovir, as well as against resistant herpesvirus strains where Aciclovir does not work. The approach prevented viral infection.

Since all types of herpes viruses have similar structure and physical properties, this antiviral treatment works on all types of viruses within the herpes family.

"The drugs available today for combatting viral infections are highly specialised against the viral proteins, and if the virus mutates, which regularly occurs, the drug is rendered ineffective. However, if you succeed in developing a treatment that attacks the physical properties of a virus, such as lowering the pressure inside the herpes virus shell, it should be possible to counter many different types of viral infections within the same virus family using the same drug. In addition, it would work even if the virus mutates because the mutations do not affect the internal pressure of the herpes virus.

"The result of the present study is a first step towards the goal of developing a drug and we already have positive preliminary data showing that a herpes infection can be stopped for all types of herpes virus including the resistant strains."

A UB study published in the journal Neurotherapeutics has validated a new pharmacological target for Alzheimer's disease. The results show the inhibition of the enzyme soluble epoxide hydrolase (sEH) in murine models with the disease reduces the neuroinflammatory process, improving the endogen response of the organism and reducing the neuronal damage and death that cause this type of dementia.

These results confirm the role of this enzyme in the evolution of Alzheimer's disease and pinpoint its inhibition as a potential strategic target for this disease and for others that feature neuroinflammation.

The new study is led by the lecturers of the Faculty of Pharmacy and Food Sciences Mercè Pallàs (Institute of Neurosciences), Santiago Vázquez (Institute of Biomedicine of the UB - IBUB) Carles Galdeano (IBUB), and Christian Griñán-Ferré (Institute of Neurosciences of the University of Barcelona - UBNeuro). Other participants are the experts of the Institute of Biomedical Research of Barcelona (IIBB) -- from CSIC and IDIBAPS--, the Autonomous University of Barcelona, the University of Santiago de Compostela and the California Davis University.

A strategy focused on inflammatory processes

The drugs that are currently used to treat Alzheimer's disease have a limited efficiency and only in light phases of the disease. The therapeutic strategies of the last years have been specifically targeted at counterbalancing molecular paths such as the accumulation of amyloid beta and the formation of plaques in the brain, typical in this pathology. In the study, researchers used a new approach related to the inflammatory processes that contribute to unchain this disease and shape its pathogenesis. "It is important to expand the research on the therapy to treat Alzheimer's towards new pharmacological targets, preferably related to pathophysiological pathways of the disease. In this case, our interest lied on sEH, since its inhibition showed powerful anti-inflammatory effects and some of its inhibitors were or had been in clinical phases in the treatment for hypertension, anti-inflammatory processes and neuropathic pain", notes Mercè Pallàs.

The enzyme sEH is present in the whole organism and which is relatively abundant in the murine and human brains. This enzyme makes the epoxyeicosatrienoic acids (EETs), molecules that reduce the inflammatory response under pathological conditions such as hypertension or diabetes, lose their anti-inflammatory activity and can even cause inflammation. Given these background, researchers analysed the effects of the inhibition of she in two animal models with Alzheimer's disease, one regarded as familiar Alzheimer's and the other linked to the progress of the disease with advanced ages. The first part of the study showed that the expression of this enzyme increased in two animal models -compared to the control group- as well as in brain samples from patients with Alzheimer's. "These findings make the sEH to be linked to the progression of Alzheimer's and we can consider it to be a new pharmacological target", notes the researcher.

Drugs with neuroprotector effects

Once the sEH enzyme was considered a new therapeutic target, researchers validated it using three sEH inhibitors structurally different, one of them designed and synthetized by the group led by Santiago Vázquez. The results showed that all the used compounds, regardless of their chemical structure, were able to prevent cognitive deterioration in both animal models. "The oral treatment with different drugs allowed us to stop the cognitive damage and reduced all markers of the disease, such as the accumulation of amyloid plaques, tau phosphorylation, endoplasmic reticulum stress, and oxidative stress", notes Mercè Pallàs.

Moreover, the new therapeutic strategy can have implications in the treatment of other pathologies. "sEH leading to an increase of endogen antiinflamatory defenses in the organism means the inhibitors of the enzyme can be an appropriate, efficient and safe therapy in pathologies that feature inflammation", notes Santiago Vázquez. The researcher adds that they are assessing new inhibitors of sEH patented by the University of Barcelona not only in models for Alzheimer's disease but also in models of Niemann-Pick type C disease, neuropathic pain and acute pancreatitis, all of them with an important inflammatory element.

Dublin, Friday, 24 July 2020: The COVID-19 pandemic is a catalyst to accelerate the adoption of technology-enabled patient care for epilepsy, according to a new study published in Epilepsia.

Building on the HSE eHealth Ireland funded Epilepsy Lighthouse Project, the research was led by FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, hosted by RCSI University of Medicine and Health Sciences. Funding for the project has continued through the Health Research Board (HRB) Applied Partnership Award.

The study describes an electronic patient portal for people with epilepsy that has been developed for patients in Ireland. Named PiSCES (providing individualised services and care for people with epilepsy), the portal is linked to the Irish National Epilepsy Electronic Patient Record.

PiSCES gives people access to their medical record documenting their epilepsy care anywhere there is an internet connection using a smartphone, tablet device or desktop computer. Users of PiSCES can access their clinic visit summaries and tools to report outcomes, such as frequency of seizures. The portal also allows people to track epilepsy care goals and send secure messages directly to their healthcare provider.

"Our work on the development of PiSCES patient portal for epilepsy began before the COVID-19 crisis with the aim of facilitating better patient and family-centred epilepsy care by improving the link between people with epilepsy and their clinicians," commented Mary Fitzsimons, eHealth Lead at FutureNeuro, RCSI.

"The COVID-19 pandemic has increased the urgency to accelerate much needed health service reform to implement innovations such as electronic patient portals. PiSCES has the capability to transform out-patient care for people with epilepsy, by maximizing health service resources that may be constrained in the aftermath of the pandemic.

"In the aftermath of COVID-19, it is highly unlikely that the healthcare sector will return to a 'business as usual' way of delivering services as we knew them previously. The pandemic is has been a catalyst for change in how patient care will be conducted in the future, delivering technology-enables care that is more responsive to individual patient needs and preferences," she said.

The research was carried out in collaboration with the Health Service Executive (HSE), Beaumont Hospital, St James's Hospital, DCU and Ergo. Dr Kevin Power, Research Engineer at RCSI and Futureneuro is first author on the paper.

Brendan Dunleavy, Head of Software Development Ergo Group said, "We are delighted to be part of this group that looks to utilise cloud and web technology to help support people with epilepsy. This is another step on the path to a true patient-centric approach to delivering acute clinical care services.

We have seen that COVID-19 has been an accelerator for technology adoption across industries and healthcare has been no exception. We look forward to seeing this work being used as an exemplar of empowering people with epilepsy."