What you need to know about Pfizer’s anti COVID-19 drug Paxlovid

The FDA has authorized Pfizer’s Paxlovid for emergency use* to treat COVID-19 patients at high risk of hospitalization or death. Paxlovid can slow the replication of the virus that causes COVID, but it has the potential for dangerous interactions with drugs commonly prescribed for diabetes, heart disease, and many other conditions.

High risk patients are often those who have not been vaccinated, and/or have a number of comorbidities (additional, chronic health problems) such as hypertension, diabetes, hyperlipidemia, depression, and cancer.

Patients already taking multiple drugs to control chronic diseases, could be effected by harmful drug interactions between the their current drugs and Paxlovid. Awareness of potential drug-drug interactions may help to avoid severe adverse drug reactions and improve efficacy of Paxlovid’s anti-COVID-19 activity.

Paxloid contains two medicines in two separate tablets, nirmatrelvir and ritonavir. The drug’s anti-COVID-19 activity relies on the inhibition of SARS-CoV-2 Mpro enzyme activity by nirmatrelvir, which results in inhibition of virus replication. Nirmatrelvir is a substrate of cytochrome P450 CYP3A4 for metabolism.

Ritonavir is an HIV drug that inhibits CYP3A4 and slows the metabolism of Nirmatrelvir, therefore enhancing efficacy of anti-virus activity of Nirmatrelvir.

Spleen function discovery could lead to better treatments for infectious diseases

An advanced fluorescent microscopy image of the complex networks of stromal cells that construct the spleen and support immune responses.
Image: Professor Scott Mueller

Researchers at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) have discovered a new gene that plays an important role in the way the spleen functions, potentially leading to new treatments for infectious diseases.

The study, published in Science Immunology, also uncovered multiple new spleen cells and revealed the distinct way they respond in order to fight off different infections.

The spleen plays a key role in the immune responses that protect the body against various diseases and infections such as virus infections, malaria and sepsis, and also plays a key role in the immune response to vaccines. However, it has not been known how the spleen functions to support this response.

University of Melbourne Professor Scott Mueller, a Laboratory Head at the Doherty Institute and lead author on the paper, explained that while it is known the spleen is made up of various networks of cells called fibroblasts, a clear picture of how these cells are constructed and function, was lacking.

“Using novel biological tools and next generation sequencing, we were able to examine precisely how specialized types of fibroblast cells dictate how the spleen works to protect against infections,” Professor Mueller explained.

Common clay materials may help curb methane emissions

A team of researchers at MIT has come up with a promising approach to controlling methane emissions and removing it from the air, using an inexpensive and abundant type of clay called zeolite. In this image, the zeolite, depicted as the complex structure in the middle, absorbs the methane that passes through it.
Credits:Image: Darius Siwek

Methane is a far more potent greenhouse gas than carbon dioxide, and it has a pronounced effect within first two decades of its presence in the atmosphere. In the recent international climate negotiations in Glasgow, abatement of methane emissions was identified as a major priority in attempts to curb global climate change quickly.

Now, a team of researchers at MIT has come up with a promising approach to controlling methane emissions and removing it from the air, using an inexpensive and abundant type of clay called zeolite. The findings are described in the journal ACS Environment Au, in a paper by doctoral student Rebecca Brenneis, Associate Professor Desiree Plata, and two others.

Although many people associate atmospheric methane with drilling and fracking for oil and natural gas, those sources only account for about 18 percent of global methane emissions, Plata says. The vast majority of emitted methane comes from such sources as slash-and-burn agriculture, dairy farming, coal and ore mining, wetlands, and melting permafrost. “A lot of the methane that comes into the atmosphere is from distributed and diffuse sources, so we started to think about how you could take that out of the atmosphere,” she says.

T cells from common colds cross-protect against infection with SARS-CoV-2

People with higher levels of T cells from common cold coronaviruses are less likely to become infected with SARS-CoV-2.

A new study, published in Nature Communications and led by Imperial College London researchers, provides the first evidence of a protective role for these T cells. While previous studies have shown that T cells induced by other coronaviruses can recognize SARS-CoV-2, the new study examines for the first time how the presence of these T cells at the time of SARS-CoV-2 exposure influences whether someone becomes infected.

The researchers also say their findings provide a blueprint for a second-generation, universal vaccine that could prevent infection from current and future SARS-CoV-2 variants, including Omicron.

Dr Rhia Kundu, first author of the study, from Imperial’s National Heart & Lung Institute, says: “Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why. We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection.

"Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why." Dr Rhia Kundu National Heart & Lung Institute

"While this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone. Instead, the best way to protect yourself against COVID-19 is to be fully vaccinated, including getting your booster dose.”

The study began in September 2020 when most people in the UK had neither been infected nor vaccinated against SARS-CoV-2. It included 52 people who lived with someone with PCR-confirmed SARS-CoV-2 infection and who had therefore been exposed to the virus. The participants did PCR tests at the outset and 4 and 7 days later, to determine if they developed an infection.

80 percent of the skin replaced

After his treatment, the boy was able to do normal work again.
Credit: Catholic Clinic Bochum

New skin from genetically modified stem cells had never been used on such a large area. The patient is stable five years later.

The case is considered unique worldwide: in 2015, a German-Italian team replaced 80 percent of its skin with its genetically modified stem cells for a boy who was then seven years old. He suffered from the life-threatening butterfly disease Epidermolysis bullosa. Those affected have extremely thin skin, which blows, tears and dissolves even with minimal external influences. Around five years later, the skin is stable and has the same sensory qualities as healthy skin. The treatments from the Center for Regenerative Medicine at the University of Módena (Italy) and the Fire Injury Center of the Ruhr University Bochum (RUB) report in the magazine New England Journal of Medicine from 9. December 2021.

The skin is stable, the immune system intact

After all conservative and surgical therapy attempts were unsuccessful at the time, the international team, the small patient, succeeded Remove skin, process it genetically and then transplant it to the wound surfaces This method had never been used on such a large skin area.

Childhood vaccination: the benefits spread beyond children

Professor Michael Good from the Institute for Glycomics, Griffith University

An Australian and Canadian study has found while childhood COVID vaccination leads to high relative reductions in child disease and mortality, it is more beneficial to adults, particularly the unvaccinated.

Accepted into mBio, but available currently on MedRxiv, the research uses a mathematical epidemiological model to forecast the effect of childhood vaccination on the number of COVID-19 cases, hospitalizations, deaths, complications, and vaccine adverse effects in both children and in adults.

“Our model showed that childhood vaccination carries minimal risk, yet can result in large relative reductions in the disease” said Professor Michael Good from the Institute for Glycomics, Griffith University.

Professor Michael Good from the Institute for Glycomics, Griffith University

“For children between 5-11 years of age while we will see a high percent reduction in hospitalizations and deaths, there will not be a huge reduction in the actual number of children being hospitalized or dying because these events were so rare in the first place, even in unvaccinated children.”

The study showed that the biggest benefit of childhood vaccination will, perhaps surprisingly, be seen in adult populations.

“A critical point is that for children aged 5-11 cases of vaccine-associated myocarditis and anaphylaxis are predicted to be very rare, so childhood vaccination can be used altruistically to work for the greater population,” said Professor Michael Hawkes, School of Public Health, University of Alberta.

Circumbinary Planet Discovered by TESS Validates New Detection Technique

The newly discovered planet, TIC 172900988b, is roughly the radius of Jupiter, and several times more massive, but it orbits its two stars in less than one year. This world is hot and unlike anything in our Solar System. 
Credit: PSI/Pamela L. Gay.

A new technique developed in part by Planetary Science Institute Senior Scientist Nader Haghighipour has allowed astronomers to quickly detect a transiting circumbinary planet orbiting around two suns, according to a new Astronomical Journal paper on which Haghighipour is an author.

Circumbinary planets are planetary bodies that rotate around two stars. Although for years, they were merely a matter of science fiction, thanks to the successful operation of NASA’s Kepler and Transiting Exoplanet Survey Satellite (TESS) telescopes, an all-sky survey mission designed to discover thousands of exoplanets around nearby bright stars, a team of astronomers, including Haghighipour, have detected 14 such bodies.

“Detecting circumbinary planets is much more complicated than detecting planets orbiting single stars. The most promising technique for detecting circumbinary planets is transit photometry, which measures drops in starlight caused by those planets whose orbits are oriented in space such that they periodically pass between their stars and the telescope. In this technique, the measurements of the decrease in the intensity of the light of a star is used to infer the existence of a planet,” Haghighipour said. “To determine the orbit of the planet, precisely, at least three transit events are required. This becomes complicated when a planet orbits a double-star system because transits will not happen with the same interval over the same star. The planet may transit one star and then transit the other before transiting the first star again, and so on.”

Anxiety and PTSD linked to increased myelin in brain

A series of fMRI scans of the brain of a military veteran with PTSD, showing gray matter regions with increased myelin. 
Credit: UCSF image by Linda Chao

A recent study links anxiety behavior in rats, as well as post traumatic stress disorder (PTSD) in military veterans, to increased myelin — a substance that expedites communication between neurons — in areas of the brain associated with emotions and memory.

The results, reported by scientists at the University of California, Berkeley, and UC San Francisco (UCSF), provide a possible explanation for why some people are resilient and others vulnerable to traumatic stress, and for the varied symptoms — avoidance behavior, anxiety and fear, for example — triggered by the memory of such stress.

If, as the researchers suspect, extreme trauma causes the increased myelination, the findings could lead to treatments — drugs or behavioral interventions — that prevent or reverse the myelin production and lessen the aftereffects of extreme trauma.

Myelin is a layer of fatty substances and proteins that wraps around the axons of neurons — essentially, the insulation around the brain’s wiring — to facilitate long-distance transmission of signals and, thus, communication between distant areas of the brain. The inner regions of the brain look white — in fact, they are referred to as “white matter” — because of the myelin encasing the many large bundles of axons there.

Dog brains can distinguish between languages

Credit: Photo: Eniko Kubinyi

"Some years ago I moved from Mexico to Hungary to join the Neuroethology of Communication Lab at the Department of Ethology, Eötvös Loránd University for my postdoctoral research. My dog, Kun-kun, came with me. Before, I had only talked to him in Spanish. So I was wondering whether Kun-kun noticed that people in Budapest spoke a different language, Hungarian.” — says Laura V. Cuaya, first author of the study. “We know that people, even preverbal human infants, notice the difference. But maybe dogs do not bother. After all, we never draw our dogs' attention to how a specific language sounds. We designed a brain imaging study to find this out.

Kun-kun and 17 other dogs were trained to lay motionless in a brain scanner, where we played them speech excerpts of The Little Prince in Spanish and Hungarian. All dogs had heard only one of the two languages from their owners, so this way we could compare a highly familiar language to a completely unfamiliar one. We also played dogs scrambled versions of these excerpts, which sound completely unnatural, to test whether they detect the difference between speech and non-speech at all.”

When comparing brain responses to speech and non-speech, researchers found distinct activity patterns in dogs’ primary auditory cortex. This distinction was there independently from whether the stimuli originated from the familiar or the unfamiliar language. There was, however, no evidence that dog brains would have a neural preference for speech over non-speech.

"Dog brains, like human brains, can distinguish between speech and non-speech.

New way to alter DNA, affect health circumvents gut bacteria

John Denu

Our gut microbiome helps us out every day by processing the fiber we can’t digest. The bacteria ferment the fiber into key chemicals known as short-chain fatty acids, or SCFAs, that are essential for human health. SCFAs fight inflammation, help kill dangerous bacteria, protect the lining of the gut, and can even help prevent cancer.

In a new study, the John Denu lab at the University of Wisconsin–Madison’s Wisconsin Institute for Discovery has learned that the fatty acids butyrate and propionate also activate p300, a crucial human enzyme that promotes the unspooling of DNA. This unwound DNA allows more genes to become active and expressed, which ultimately affects human health.

Previous research had suggested that SCFAs might instead contribute to this process by inhibiting a different set of enzymes.

This new understanding opens the possibility of activating p300 in a diet-dependent way or even independently of the microbiome. Knowing how to target p300 is vital because it is implicated in a wide variety of physiological processes and diseases, such as propionic acidemia, autism spectrum disorder, and Alzheimer’s disease.

Sydney Thomas

“Knowing that butyrate and propionate directly interact with this protein opens up a lot of new areas of research that we didn’t even think to look at before, because we thought that it was happening the opposite way than it actually is,” says Sydney Thomas, a Denu lab graduate student and co-author on the paper.

Thomas and Denu, a professor of biomolecular chemistry, published their findings in the journal eLife.

Earlier work in mice had shown that SCFAs are a crucial link between the microbiome and epigenetic states — the modifications to DNA that affect how active any given gene is. These epigenetic modifications allow different cells to use the same DNA instructions to perform different tasks and can affect health.

Cystic Fibrosis Drugs Can Be ‘Life-Changing’ For Patients

Small molecule drugs (outlined in green) nestle in a cavity in the protein that malfunctions in cystic fibrosis, stabilizing the protein and correcting its flaws.
Credit: K. Fiedorczuk et al./ Cell 2022

Just over a decade ago, in one of the great advances in modern medicine, researchers at Aurora Biosciences and then Vertex Pharmaceuticals found what they described at the time as needles in a haystack – small molecule drugs that can treat cystic fibrosis, the lung-damaging genetic disease.

Vertex’s first drug, ivacaftor, was approved in 2012, and others followed, dramatically increasing survival age and quality of life for cystic fibrosis patients. The drugs improve lung function, allowing patients to breathe better. Scientists knew that the drugs somehow adjusted or corrected the faulty protein responsible for the disease, but how they work has remained unknown.

Now, in new work that reveals the structure of the mutated protein and how so-called corrector drugs interact with it, Howard Hughes Medical Institute Investigator Jue Chen’s team at the Rockefeller University has discovered how the molecules operate. They bind to and stabilize the defective protein during its biogenesis, giving it a better chance to successfully reach the cell surface, her team reports January 6, 2022, in the journal Cell.

Why people deceive themselves

A team of philosophy from the Ruhr University Bochum (RUB) and the University of Antwerp analyzed the role of self-deception in everyday life and the strategies people use to fool themselves. In the journal Philosophical Psychology, Dr. Francesco Marchi and Prof. Dr. Albert Newen's four strategies to stabilize and shield the positive self-image. According to their theory, self-deception helps people to maintain motivation in difficult situations. The article is on 6. January 2022.

Four strategies of self-deception

“All people are deceiving themselves, and not so rare ”, says Albert Newen of the RUB Institute for Philosophy II. “For example, if a father is convinced, that his son is a good student and then brings bad grades home, maybe he'll say first, that the subject is not so important or that the teacher has not explained the material well. “The researchers describe this strategy of self-deception as a reorganization of beliefs. In their article, they describe three other strategies that people often use and that start earlier so as not to allow unpleasant facts to be applied to one.

This includes selecting facts through targeted action: people avoid places or people who could bring problematic facts to them, such as the parents' day. Another strategy is to reject facts by expressing doubts about the credibility of the source. As long as the father only indirectly hears about his son's school problems and does not see the grades, he can ignore the problems. Newen and Marchi describe the last strategy as the generation of facts from an ambiguous situation: “If, for example, the friendly math teacher makes it easy to understand, that the son cannot cope and the father would have expected a clear announcement in the event of difficulties, he may interpret the great friendliness and cautious description as a positive assessment of his son's abilities ”, Francesco Marchi explains the example.

Research suggests foliar fungicides help increase soybean yield in some regions

While previous studies have shown little economic benefit associated with using foliar fungicides in soybean as a preventive measure, new research aided by a Penn State plant pathologist suggests otherwise, especially in southern regions.

The findings will help growers in the U.S. understand how foliar fungicides — applied to leaves — fit into overall soybean production practices, noted Paul Esker, associate professor of epidemiology and field crop pathology in the College of Agricultural Sciences, who collaborated with Denis Shah, associate scientist in the Department of Plant Pathology, Kansas State University.

Soybean is one of the major crops produced in the U.S., planted on an estimated 87.6 million acres in 2020. Esker explained that success in growing soybean depends on multiple management decisions, including choice of cultivar, sowing date, seeding rate, nutrient fertilization, irrigation, drainage, crop rotation and tillage.

Foliar fungicides — used to prevent fungal plant diseases such as frogeye leaf spot and brown spot — are another management consideration. These diseases can flourish when temperatures are warm with humid conditions, such as those that occur in regions known for producing soybean. These fungal diseases have the potential to impact crop health and yield.

Previous field trials have demonstrated that when there is little or no disease present, there is no economic benefit to using foliar fungicides, Shah and Esker explained. Despite that information, the use of foliar fungicides in U.S. soybean production almost tripled from 2005 to 2015.

Tackling the Plastics Problem

Despite the society-changing improvements that plastic materials have brought to humanity, there’s no question that they also present us with new challenges regarding what to do with the large amounts of plastic waste we generate, from the oil-based chemicals used to create products to the microplastics found everywhere after plastics breakdown in the environment.

Finding a solution to plastics pollution that will work in the lab and in the real world will take a diverse team of innovative individuals with expertise that transcends the incredible talent found at the University of Delaware. That’s why researchers from UD’s College of Engineering and Biden School of Public Policy and Administration are joining forces with experts at the University of Kansas and Pittsburg State University.

“The practices by which society works now are really not sustainable,” said Raul Lobo, Claire D. LeClaire Professor of Chemical Engineering and associate department chair in UD’s Department of Chemical and Biomolecular Engineering, who is leading the research effort for UD. “We need materials that minimize our dependency on fossil fuels and that allow consumers to recycle plastic products efficiently and with ease.To this end, the UD-KU team will develop new molecules that can be used to make a new generation of environmentally friendly plastics.”

The National Science Foundation’s Experimental Program to Stimulate Competitive Research has awarded the group $4 million in funding to do just that. About $1.4 million of that funding will go to UD to support this vast research effort to develop processes to transform “biomass,” such as agricultural byproducts, into commercially viable plastics materials and to chemically deconstruct such plastics effectively and efficiently so that they can be recycled and reused.

Southern California mountain lions show first reproductive effects of inbreeding

The mountain lion known as P-81, pictured here, is among the first in the Santa Monica Mountains with a tail defect.
Credit: National Park Service

Southern California cougars often make the news with their litters of oh-so-cute kittens, but a UCLA-led study suggests that these mountain lions may soon find it much harder to reproduce due to a lack of genetic diversity.

Scientists tracking two local mountain lion populations, one in the Santa Monica Mountains and another in the Santa Anas, have identified the first reproductive signs of inbreeding among these groups, which are cut off from other cougar populations — and therefore breeding options — by busy freeways.

The animals averaged a whopping 93% abnormal sperm rate, while some also displayed physical signs of inbreeding, like deformed tails or testicular defects. Researchers have long had genetic evidence of inbreeding, but the malformed sperm is the first evidence that inbreeding is manifesting in the reproductive system.

“This is a serious problem for an animal that’s already endangered locally,” said the study’s lead author, Audra Huffmeyer, a UCLA postdoctoral researcher who studies fertility in large cat species and is a National Geographic Explorer. “It’s quite severe.”