Culture

SPOKANE, Wash. - Touching patients while providing care is an important and unavoidable aspect of the nursing profession. Nurses can also transform touch into a useful therapeutic tool to improve patients'-- and their own--wellbeing.

That is the topic of a study, "'Permission to Touch': Nurses' Perspectives of Interpersonal Contact during Patient Care," published in the Western Journal of Nursing Research.The authors include two Washington State University College of Nursing faculty, Associate Professor Marian Wilson and Assistant Professor Tullamora Landis, former faculty member Michele Shaw, and lead author Enrico DeLuca, of Sapienza University of Rome, Italy, who visited WSU in 2018 to work with Wilson on the study.

Nurses touch patients frequently for tasks and to provide comfort and emotional support. Studies have looked at physical contact occurring during nursing care, offering several definitions. "Expressive" touch, for example, is spontaneous and used to establish contact, reassure or give comfort, such as laying a hand on a patient's shoulder.

Most previous studies have looked at the effect of such touch on patients; this study looks at how interpersonal contact is perceived by nurses. Nurses were also asked about their view of massage as a form of intentional touch in a clinical setting.

Through focus groups and interviews, participants said they found touch and massage helpful when providing patient care and saw them as especially important resources in providing emotional care.

Said one participant, "... there are also times when your patient needs extra emotional support and putting a hand on a shoulder, holding a hand, that can be really, really effective and that's something I use quite often."

Participants, however, also expressed concerns about boundaries and discussed how they assessed whether a patient was open to interpersonal touch.

The study noted that touch and massage techniques are useful tools that are already being employed by many nurses, but that it would be helpful to clarify the types of interpersonal contact used by nurses and possibly include touch as a competency in nursing education.

Creating the best conditions for cells to make energy and survive critical illness is a challenge little understood in modern medicine. Now a new study led by scientists at the University of Plymouth, in collaboration with University College London and the Universities of Cambridge and Southampton, shows early signs that cells in some critically ill patients actually adapt to their conditions by producing energy more efficiently.

The research, published in the journal Redox Biology, took muscle and blood samples over seven days from 21 critically ill patients (ie those with two or more organs failing) in intensive care, and 12 healthy people, comparing cells' behaviour.

The study showed that all of the critically ill patients produced energy more efficiently than healthy people, in a pattern of changes that has previously been identified in cells adapting to low oxygen levels. There were also differences in the ways cells produced energy in the patients who survived, compared to those who died.

So how was this measured? In mitochondria (the powerhouses of our cells), structures known as 'complexes' transport electrons, which, facilitated by oxygen inhalation, effectively becomes the fuel driving our cells. The study showed that the capacity of one of these complexes was 27% lower in survivors than in non-survivors after 48 hours of illness, but tended to increase in seven days, with no such recovery observed in non-survivors. This means that, despite this complex appearing to work at a lower rate, the cells were adapting to the adverse conditions of the critical illness, and coming out the other side.

The work was funded by the Intensive Care Society, and forms part of the University of Plymouth's expertise in intensive care medicine, which explores oxygen deprivation and the body's ability to cope in hostile conditions.

It also builds on principles of Nobel prize-winning research from 2019, by William Kaelin, Sir Peter Ratcliffe and Gregg Semenza, which uncovered how cells respond to changes in oxygen levels.

Lead author Dr Helen McKenna, National Institute for Health Research Academic Clinical Fellow at the University of Plymouth, explains why the new work is important.

"When a body is going through trauma, there's the temptation to think we need to give more oxygen or stimulate cells to survive," she said. "However, this research suggests that some cells can actually adapt to the conditions they're in.

"Of course the next question to answer is why some people's cells behave in this way while others' don't. It could be genetics, age or previous exposure to trauma - we don't yet know. But uncovering this cell behaviour in the first place is a really important step. If we can unravel the cellular and molecular foundation of human resilience, we can enable the development of more effective life-support strategies."

Few sites in the world preserve a continuous archaeological record spanning millions of years. Wonderwerk Cave, located in South Africa's Kalahari Desert, is one of those rare sites. Meaning "miracle" in Afrikaans, Wonderwerk Cave has been identified as potentially the earliest cave occupation in the world and the site of some of the earliest indications of fire use and tool making among prehistoric humans.

New research, published in Quaternary Science Reviews, led by a team of geologists and archaeologists from the Hebrew University of Jerusalem (HU) and the University of Toronto, confirms the record-breaking date of this spectacular site. "We can now say with confidence that our human ancestors were making simple Oldowan stone tools inside the Wonderwerk Cave 1.8 million years ago. Wonderwerk is unique among ancient Oldowan sites, a tool-type first found 2.6 million years ago in East Africa, precisely because it is a cave and not an open-air occurrence," explained lead author Professor Ron Shaar at HU's Institute of Earth Sciences.

The team were able to successfully establish the shift from Oldowan tools (mainly sharp flakes and chopping tools) to early handaxes over 1 million years ago, and to date the deliberate use of fire by our prehistoric ancestors to 1 million years ago, in a layer deep inside the cave. The latter is a particularly significant because other examples of early fire use come from open-air sites where the possible role of wildfires cannot be excluded. Moreover, Wonderwerk contained a full array of fire remnants: burnt bone, sediment and tools as well as the presence of ash.

Dating cave deposits is one of the greatest challenges in paleo-anthropology, aka the study of human evolution. To overcome this challenge, the team analyzed a 2.5-meter thick sedimentary layer that contained stone tools, animal remains and fire remnants using two methods: paleomagnetism and burial dating. "We carefully removed hundreds of tiny sediment samples from the cave walls and measured their magnetic signal," described Shaar.

Magnetization occurred when clay particles, that entered the cave from outside, settled on the prehistoric cave floor, thereby preserving the direction of the earth's magnetic field at that time. "Our lab analysis showed that some of the samples were magnetized to the south instead of the north, which is the direction of today's magnetic field. Since the exact timing of these magnetic "reversals" is globally recognized, it gave us clues to the antiquity of the entire sequence of layers in the cave," added Shaar.

Prof. Ari Matmon, Director of HU's the Institute of Earth Sciences, relied on a secondary dating method to further confirm when the earliest "humans" may have occupied the site. "Quartz particles in sand have a built-in geological clock that starts ticking when they enter a cave. In our lab, we are able to measure the concentrations of specific isotopes in those particles and deduce how much time had passed since those grains of sand entered the cave," he explained.

The dating of prehistoric human activity at Wonderwerk Cave has far-reaching implications. The co-directors of the Wonderwerk Cave project, Prof. Michael Chazan at the University of Toronto and Liora Kolska Horwitz at HU's National Natural History Collections, explained that the findings at Wonderwerk "are an important step towards understanding the tempo of human evolution across the African continent. With a timescale firmly established for Wonderwerk Cave, we can continue studying the connection between human evolution and climate change, and the evolution of our early human ancestors' way of life."

On the southern edge of the Kalahari Desert, Wonderwerk Cave is also a place of great spiritual significance to local communities, attesting to the cave's cultural importance for both past and present peoples. The Wonderwerk Cave Research Project is committed to protecting the site and to working with neighboring towns to develop the educational and cultural potential of this unique place.

Photos, Credits and Article available at https://drive.google.com/drive/folders/103a60qIZCOi9zzRFUUzP376ZG4KHWvP_?usp=sharing

Australian researchers have identified neutralising nanobodies that block the SARS-CoV-2 virus from entering cells in preclinical models.

The discovery paves the way for further investigations into nanobody-based treatments for COVID-19.

Published in PNAS, the research is part of a consortium-led effort, bringing together the expertise of Australian academic leaders in infectious diseases and antibody therapeutics at WEHI, the Doherty Institute and the Kirby Institute.

At a glance

Researchers have identified nanobodies that effectively blocked the SARS-CoV-2 virus from entering cells in pre-clinical models of COVID-19 infection.

Nanobodies - which are tiny immune proteins - could provide an alternative to conventional antibody treatments for COVID-19.

By mapping nanobodies, the research team was able to identify a nanobody that recognised the SARS-CoV-2 virus, including emerging global variants of concern. The nanobody also recognised the original SARS-CoV virus (which causes SARS), indicating it may provide cross-protection against these two human coronaviruses.

Using alpaca 'nanobodies' to block COVID-19 infection

Antibodies are key infection-fighting proteins in our immune system. An important aspect of antibodies is that they bind tightly and specifically to another protein.

Antibody-based therapies, or 'biologics', harness this property of antibodies, enabling them to bind to a protein involved in disease.

Nanobodies are unique antibodies - tiny immune proteins - produced naturally by alpacas in response to infection.

As part of the research, a group of alpacas in regional Victoria were immunised with a synthetic, non-infectious part of the SARS-CoV-2 'spike' protein to enable them to generate nanobodies against the SARS-CoV-2 virus.

WEHI Associate Professor Wai-Hong Tham, who led the research, said the establishment of a nanobody platform at WEHI allowed an agile response for the development of antibody-based therapies against COVID-19.

"The synthetic spike protein is not infectious and does not cause the alpacas to develop disease - but it allows the alpacas to develop nanobodies," she said.

"We can then extract the gene sequences encoding the nanobodies and use this to produce millions of types of nanobodies in the laboratory, and then select the ones that best bind to the spike protein."

Associate Professor Tham said the leading nanobodies that block virus entry were then combined into a 'nanobody cocktail'.

"By combining the two leading nanobodies into this nanobody cocktail, we were able to test its effectiveness at blocking SARS-CoV-2 from entering cells and reducing viral loads in preclinical models," she said.

Mapping nanobody binding

ANSTO's Australian Synchrotron and the Monash Ramaciotti Centre for Cryo-Electron Microscopy were critical resources in the project, allowing the research team to map how the nanobodies bound to the spike protein and how this impacted the virus' ability to bind to its human receptor.

Hariprasad Venugopal, Senior Microscopist from the Monash Ramaciotti Centre for Cryo-Electron Microscopy, said the study highlighted the importance of open-access to high-end Cryo-EM facilities.

"We were able to directly image and map the neutralising interaction of the nanobodies with the spike protein using Cryo-EM at near atomic resolution," Mr Venugopal said.

"Cryo-EM has been an important drug discovery tool in the global response to the COVID-19 pandemic."

By mapping the nanobodies, the research team was able to identify a nanobody that recognised the SARS-CoV-2 virus, including emerging global variants of concern. The nanobody was also effective against the original SARS virus (SARS-CoV), indicating it may provide cross-protection against these two globally significant human coronaviruses.

"In the wake of COVID-19, there is a lot of discussion about pandemic preparedness. Nanobodies that are able to bind to other human beta-coronaviruses - including SARS-CoV-2, SARS-CoV and MERS - could prove effective against future coronaviruses as well," Associate Professor Tham said.

MUNICH -- Rewilding--a hands-off approach to restoring and protecting biodiversity--is increasingly employed across the globe to combat the environmental footprint of rapid urbanization and intensive farming. The recent reintroduction of grey wolves in Yellowstone, America's first national park, is regarded as one of the most successful rewilding efforts, having reinvigorated an ecosystem that had been destabilized by the removal of large predators.

However, successful attempts to rewild the landscape hinge on more than just the reintroduction of a plant or animal species, they also require that geography and geology be taken into account, according to new research from the University of Amsterdam and the Dutch State Forestry Service.

It is the landscape that ultimately decides the outcome of rewilding efforts, says Kenneth Rijsdijk, an ecologist at the University of Amsterdam, who is presenting the team's results at the European Geosciences Union (EGU) General Assembly 2021.

One of the key challenges of rewilding is deciding where to do it, Rijsdijk says, especially given competing land-uses like infrastructure and agriculture. "Clearly, we cannot, and should not, rewild everywhere. It makes sense to pick out specific areas where rewilding is more likely to succeed, taking into account how landscape features, like ruggedness and soil nutrients, can shape ecosystems."

Ecologists gauge rewilding success using biodiversity metrics, such as an increase in the abundance and diversity of plant or bird species. But these measurements do not factor in the role of landscape: from the topography and river systems to the soil and underlying geology.

These aspects--known collectively as geodiversity--furnish all the physical support required for life on Earth. "Landscape plays a pivotal role in defining the ecosystem: determining where vegetation grows, herbivores graze, animals seek shelter, and predators hunt," Rijsdijk says.

"It's remarkable that, from a conservation standpoint, the landscape itself is significantly undervalued in the success of rewilding projects," says coauthor Harry Seijmonsbergen, an ecologist at the University of Amsterdam.

The team aims to build a more holistic index for measuring and predicting rewilding success.

Early applications of their approach--in northwestern Europe, at sites previously marked by the Dutch State Forestry Service as possible candidates for rewilding--show that more varied landscapes show greater conservation potential.

Their index draws on more than a century of geological and geographical map data, which the team have mapped out across 12 sites in northwestern Europe--combining landscape features such as elevation, forested areas, openness, and quietness in order to compute a metric for landscape quality. They also studied how geodiversity influenced rewilding over time using satellite, aerial, and field data. By tuning their new index against a previously used ecological index, they were able to independently assess the relationship between biodiversity and landscape at each site.

As an independent test of landscape ruggedness, they supplemented their workflow with previously collected data from Yellowstone. The park's mountainous and varied terrain hosts niche environments for animals to hunt and shelter.

The new research could help decision-makers select future rewilding sites with the right recipe for success. "Conservation biologists have been asking how they can pinpoint sites with the right characteristics for rewilding," Rijsdijk says. "Our research is the first to start building the required toolkit to measure landscape quality and inform that choice."

Although most oncological diseases are not infectious, some viruses can cause cancer. According to the World Health Organization, two HPV subtypes account for 70% of cervical cancer cases and pre-existing conditions. Moreover, HPV considerably increases the risks of other types of cancer. Within an infected cell, a viral protein called E6 binds with human proteins from the 14-3-3 family. 14-3-3 proteins are present in cells of all eukaryotic organisms and can interact with hundreds of other important players of intracellular processes to regulate cell division, gene activity, metabolism, cell death, and intracellular signaling. If the activity of 14-3-3 proteins is disturbed, cells can become susceptible to viruses or cancer, which is a double danger in the case of HPV.

"14-3-3 proteins are abundantly present in most tissues of the human body. These proteins come in seven types (isoforms) with very similar structures and properties. For years scientists have been trying to understand why there are several practically identical substances. Understanding the mechanisms of interactions between the E6 oncoprotein and these isoforms could help develop novel antiviral therapies," said Nikolai Sluchanko, a Ph.D. in Biology, the lead researcher of the study, and the head of the group "Protein-Protein Interactions" at the Federal Research Center for Biotechnology of the Russian Academy of Sciences.

In their work, the biologists studied a complex of different human 14-3-3 isoforms with the HPV E6 protein using X-ray crystallography. Based on the obtained data, they developed an accurate model of the spatial structure of the complex that consisted of a 14-3-3 protein and the main functional fragment of a E6 protein, which is responsible for promoting oncogenic transformation. Then, the researchers used a natural compound called fusicoccin to experimentally prove that the complex stability could be significantly affected by small therapeutic molecules. In principle, this confirms the possibility to develop a drug against HPV, a virus that is carried or infected by up to 90% of the human population.

The stability of the studied complex varied greatly depending on the 14-3-3 isoform type. Having identified this pattern, the biologists ranged the isoforms by the strength of the interaction in a descending order. Importantly, the pattern in the interaction of 14-3-3 isoforms was observed not only with E6 from different HPV subtypes, but also with many other partners of 14-3-3. The team also found confirmations of their conclusions in the data of other scientific publications and in recent proteomic studies.

"We managed to identify a global pattern of interaction between the seven human 14-3-3 isoforms and their partner proteins or fragments thereof. This fundamental discovery suggests that the repertoire of 14-3-3 isoforms is cell-specific and is tightly associated with cell functions. It is likely to change when a cell adapts to external conditions or progresses through its life cycle," concluded Nikolai Sluchanko.

Researchers from Tel Aviv University have created an artificial intelligence platform that can identify the specific proteins that allow bacteria to infect the intestines - a method that paves the way for the creation of smart drugs that will neutralize the proteins and prevent disease, without the use of antibiotics. Participating in the study, which was published in the prestigious journal Science, were Ph.D. student Naama Wagner and Prof. Tal Pupko, head of the Shmunis School of Biomedicine and Cancer Research at the Faculty of Life Sciences and the new Center for Artificial Intelligence & Data Science at Tel Aviv University. The international partners in the study included researchers from Imperial College (led by Prof. Gad Frankel) and the Institute for Cancer Research in London, as well as from the Technical University and the National Center for Biotechnology in Madrid.

Intestinal diseases are caused by pathogenic bacteria that attach to our intestinal cells. Once attached, the bacteria use a kind of molecular syringe to inject intestinal cells with proteins called "effectors." These effectors work together to take over healthy cells, like hackers that take over computer servers using a combination of lines of code. However, until now scientists have not known what protein combination it is that cracks the cell's defense mechanisms. Now, the Tel Aviv University researchers' artificial intelligence platform has identified novel effectors in the bacteria, which have been experimentally tested and validated. Subsequently, laboratory experiments conducted in London successfully predicted the protein combinations that lead to the pathogenic bacteria taking over the intestines.

"In this study, we focused on a bacterium that causes intestinal disease in mice, a relative of the E. coli bacteria that cause intestinal disease in humans, so as not to work directly with the human pathogen", explains Ph.D. student Naama Wagner. "The artificial intelligence we created knows how to predict effectors in a variety of pathogenic bacteria, including bacteria that attack plants of economic importance. Our calculations were made possible by advanced machine-learning tools that use the genomic information of a large number of bacteria. Our partners in England proved experimentally that the learning was extremely accurate and that the effectors we identified are indeed the weapons used by the bacteria."

"Pathogenic bacteria are treated with antibiotics," says Prof. Tal Pupko. "But antibiotics kill a large number of species of bacteria, in the hope that the pathogenic bacteria will also be destroyed. So antibiotics are not a rifle but a cannon. Moreover, the overuse of antibiotics leads to the development of antibiotic-resistant bacteria, a worldwide problem that is getting worse. Understanding the molecular foundation of the disease is a necessary step in the development of drugs that are smarter than antibiotics, which will not harm the bacterial population in the intestines at all. This time we discovered the effectors of gut bacteria that attack rodents, but this is just the beginning. We are already working on detecting effectors in other bacteria in an attempt to better understand how they carry out their mission in the target cells they are attacking."

Management and outcomes of adults with atrial fibrillation are presented today at EHRA 2021, an online scientific congress of the European Society of Cardiology (ESC).1 The document is published in EP Europace,2 a journal of the ESC.

Atrial fibrillation is the most common heart rhythm disorder, affecting more than 40 million people globally.3 Those with the disorder have increased risks of complications including stroke, heart failure and dementia, and are twice as likely to be admitted to hospital as their peers without the condition. The economic burden of atrial fibrillation is rising, mainly due to complications and hospitalisations.4 Effective therapies exist (e.g. to prevent stroke) but are not consistently used.5

Lead author Dr. Elena Arbelo of the University of Barcelona, Spain said: "We hope the quality indicators will help institutions to assess and monitor adherence to clinical practice guidelines. Ultimately this should lead to improved quality of care for patients with atrial fibrillation."

The expert group, which included patients with atrial fibrillation, used the ESC methodology for developing quality indicators.6 Briefly, this involved: 1) identifying domains of care for the diagnosis and management of atrial fibrillation; 2) reviewing the literature and constructing candidate quality indicators for each domain; 3) selecting the final set of quality indicators through a series of votes.

Six domains of care were identified: patient assessment at baseline and follow-up, anticoagulation therapy, rate control strategy, rhythm control strategy, risk factor management, and outcomes.

Quality indicators were chosen for each domain. For example, a quality indicator in the patient assessment domain was the proportion of patients assessed for stroke risk. In the anticoagulation domain, one quality indicator was the proportion of patients appropriately prescribed this stroke prevention therapy. For risk factor management, the indicator was the proportion of patients with these factors identified (e.g. obesity, smoking, high blood pressure, obstructive sleep apnoea, alcohol excess, lack of exercise, and poor glycaemic control).

The outcomes domain describes quality indicators for the consequences of the disease (e.g. stroke, hospitalisation), complications of treatment (e.g. bleeding), and patient-reported outcomes (e.g. assessment of quality of life, symptoms, emotional well-being, and cognitive function).

A summary of the quality indicators is incorporated into ESC guidelines for the diagnosis and management of atrial fibrillation.3 "This should enhance their dissemination and uptake into clinical practice," said Dr. Arbelo. "Modern healthcare demands that we evaluate the standard of care patients receive and their outcomes. It is essential that the patient's perspective is taken into account, particularly since most atrial fibrillation therapies aim to improve symptoms, well-being, and quality of life."

The statement was developed by the European Heart Rhythm Association (EHRA) of the ESC in collaboration with the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS).

Sophia Antipolis - 24 April 2021: Atrial fibrillation can be detected during annual foot assessments in patients with diabetes, according to research presented today at EHRA 2021, an online scientific congress of the European Society of Cardiology (ESC).1

"In our study, one in six patients with diabetes had previously undiagnosed atrial fibrillation," said study author Dr. Ilias Kanellos of the European University of Cyprus, Nicosia. "This presents an opportunity to provide treatment to prevent subsequent strokes."

Diabetes is an independent risk factor for atrial fibrillation.2 Prevalence of the heart rhythm disorder is at least two-fold higher in patients with diabetes compared to those without. Although people with atrial fibrillation have a five times greater risk of stroke, anticoagulation medication is an effective preventive therapy.

Annual foot checks are advised for patients with diabetes. This is because increased blood sugars cause poor circulation, nerve damage and numbness, and could ultimately lead to foot amputation if problems go undetected.

Dr. Kanellos said: "The yearly check-up includes palpating the arteries in the feet to examine whether there is healthy blood flow. During this examination we noticed that some patients had an irregular rhythm and decided to investigate its usefulness for diagnosing atrial fibrillation."

Two podiatrists and six podologists were trained to spot rhythm abnormalities during pulse palpation of the foot arteries. They were also shown how to confirm their findings using a hand-held Doppler ultrasound device.

The 12-month observational study included 300 patients with diabetes attending their annual foot screening appointments. Patients with rhythm abnormalities during pulse palpation of their foot arteries underwent a Doppler ultrasound to verify the observations.

The average age of participants was 60 years. There were 180 men and 120 women. The researchers found that 51 patients (17%) had previously undiagnosed atrial fibrillation. The heart rhythm disorder was found in a similar proportion of men and women. Patients were advised to visit a cardiologist for an electrocardiogram (ECG) to reinforce the diagnosis and discuss treatment.

Dr. Kanellos said: "The study has identified a simple, quick, and low-cost way to identify patients with diabetes who have a heart rhythm disorder they were unaware of. This intervention has the potential to avoid strokes and preserve quality of life in this patient group."

An international team of researchers led by the University of Bergen has uncovered how organisms from crops to corals may avoid deadly DNA damage during evolution.

Our cells, and those of animals, plants and fungi, contain compartments that produce chemical fuel. These compartments contain their own DNA, which stores instructions for important cellular machinery. But this so-called oDNA (organelle DNA) can become mutated, corrupting the instructions and preventing cells making enough energy.

In humans and some other animals, a process called the "bottleneck" allows some offspring to inherit less mutated oDNA. This process needs mothers' egg cells to develop early, like in humans, where a human girl is born with all her egg cells already formed. But other organisms, from plants to fungi, don't develop these cells early - their flexible body plans mean that eggs are not "set aside" early in development.

"We wanted to know how these organisms might avoid inheriting mutations without a human-like bottleneck," said Ellen Røyrvik, a geneticist on the research team, based at UiB.

The scientists used mathematical modelling to show that a process called gene conversion - the controlled overwriting of DNA - could in theory allow some offspring to inherit less mutant oDNA without requiring a bottleneck. Using genome data, they found machinery controlling this process in plants and fungi, but also in soft corals, sponges, and algae - all organisms without fixed body plans. They also found that this machinery was most active in the parts of plants that will end up producing the seeds of the next generation, suggesting that it is indeed used to allow some offspring to inherit fewer mutations.

"Taken together, it looks like organisms without a fixed body plan - plants, fungi, corals, sponges, algae - may have adopted gene conversion to deal with oDNA mutations," said Iain Johnston, an associate professor in the Mathematics Institute at UiB, who led the research. "Humans and other animals can develop egg cells early and use a bottleneck; other organisms can use gene conversion instead."

Going forward, the team plans to explore how this overwriting of oDNA causes other issues in the organisms that use it - including crop plants, where it can cause sterility. They are also exploring the broader question of why these compartments contain oDNA at all, given the risk of mutational damage.

The research, funded by the European Research Council, will appear in
PLOS Biology.

DURHAM, N.C. - Fruits and veggies are good for you and if you are a lemur, they may even help mitigate the effects of habitat loss.

A new study sequencing the genome of four species of sifakas, a genus of lemurs found only in Madagascar's forests, reveals that these animals' taste for leaves runs all the way to their genes, which are also more diverse than expected for an endangered species.

Sifakas are folivores, meaning that the bulk of their diet is composed of leaves. Leaves can be difficult to digest and full of toxic compounds meant to prevent them from being eaten. Unlike our carefully selected spinach, tree leaves also don't taste great, and are not very nutritious.

Because of that, leaf-eaters typically have all sorts of adaptations, such as a longer digestive tract with special pouches where bacteria help break down the food.

In a new study appearing April 23 in Science Advances, researchers sequenced genomes from Coquerel's (Propithecus coquereli), Verreaux's (P. verreauxi), golden-crowned (P. tattersalli), and diademed (P. diadema) sifakas. The individuals sequenced had been wild-born but were housed at the Duke Lemur Center, with the exception of two Verreaux's sifakas, one wild and one born in captivity.

These four species are found in different habitats in Madagascar, ranging from arid deciduous forests to rainforests, but share a similar diet.

The genomes showed molecular evidence for adaptations to neutralize and eliminate leaves' toxic compounds, optimize the absorption of nutrients, and detect bitter tastes. Their genome shows patterns of molecular evolution similar to those found in other distantly related herbivores, such as the colobus monkeys from Central Africa, and domestic cattle.

Yet despite being such fine-tuned leaf-eating machines, sifakas can eat more than just leaves. They eat lots of fruits when those are in season and will also happily munch on flowers.

"Sifakas can take advantage of foods that are higher energy and are more nutrient dense, and can fall back and subsist on leaves in times of scarcity," said Elaine Guevara, assistant research professor of Evolutionary Anthropology at Duke University and lead author of the study.

This dietary flexibility may have given them an advantage over their strictly leaves-only or fruit-only cousins in the face of threats such as forest fragmentation and disturbance.

Indeed, the analysis also showed that sifakas are genetically more diverse than would be expected for a critically endangered species on an island of shrinking habitats.

"These animals do seem to have very healthy levels of genetic diversity, which is very surprising," said Guevara

Guevara and her team gauged genome heterozygosity, which is a measure of genetic diversity and an indicator of population size. Species at high risk for extinction tend to have only small populations left, and very low heterozygosity.

Sifakas do not follow this pattern and show far higher heterozygosity than other primates or other species of critically endangered mammals. Heterozygous populations tend to be more resilient to threats such as climate change, habitat loss, and new pathogens.

However, sifakas have very long generation times, averaging 17 years, so the loss of genetic diversity may take decades to become obvious. Guevara says that the genetic diversity found in this study may actually reflect how healthy populations were 50 years ago, prior to a drastic increase in deforestation rates in Madagascar.

"Sifakas are still critically endangered, their population numbers are decreasing, and habitat loss is accelerating drastically," said Guevara.

There is still room for optimism. By not being picky eaters, sifakas may be less sensitive to deforestation and habitat fragmentation than primates with more restricted diets, allowing them to survive in areas with less-than-pristine forests.

"I've seen sifakas at the Lemur Center eat dead pine needles," said Guevara. "Their diet is really flexible."

Their greater genetic diversity may therefore mean that there is still hope for sifakas, if their habitats receive and maintain protection and strategic management.

"Sifakas still have a good chance if we act. Our results are all the more reason to do everything we can to help them," said Guevara.

Strenuous efforts to prevent and treat malaria in recent decades have brought great benefits, particularly against disease caused by Plasmodium falciparum in countries in Africa and the Americas. But malaria caused by its "stealthier and more resilient cousin", P. vivax, now needs to be confronted with high priority, say Lorenz von Seidlein and Nicholas White of the Mahidol Oxford Tropical Medicine Research Unit in Bangkok, Thailand in a Perspective. The piece introduces a Collection on the prevention and treatment of P. vivax malaria in the open access journal PLOS Medicine, published ahead of World Malaria Day on April 25th.

In a Review article in the Collection, Sarah Auburn of the Menzies School of Health Research and Charles Darwin University, Darwin, Australia and colleagues discuss the epidemiology of P. vivax. The parasite is endemic in an estimated 49 countries, and the authors highlight that the main burden of resulting disease falls on young children in remote areas poorly served by health services.

Unlike P. falciparum, P. vivax has a dormant liver stage which makes the parasite more difficult to study and treat, leading to relapsing infections. As discussed by Cindy Chu of the Shoklo Malaria Research Unit, Thailand and White in a second Review article in the Collection, effective drugs are available but the 8-aminoquinolines cause hemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. This has limited the use of this class of drugs because infrastructure to support and provide G6PD testing is required prior to providing treatment.

In a further Review article, Kamala Thriemer and coauthors draw together the themes of the Collection and discuss the practicalities of the "radical cure" for P. vivax infection, aiming to eliminate all forms of the parasite in an individual and prevent malaria relapses. "The radical cure is not an optional add-on but has to be an integral part of P. vivax malaria treatment", say the authors. The Collection will also feature a range of research studies on key aspects of the prevention and treatment of P. vivax malaria and these will be published in the coming weeks.

What The Study Did: This study examines the test result positivity rate and health outcomes of maternal SARS-CoV-2 infection among perinatally exposed newborns.

Authors: Asimenia Angelidou, M.D., Ph.D., of Beth Israel Deaconess Medical Center in Boston, 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.2021.7523)

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.

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BOSTON - At the start of the COVID-19 pandemic, very little was known about SARS-CoV-2, the virus that causes COVID-19. Over the past year, more evidence has become available on how the virus is transmitted, who is at the greatest risk and best practices to prevent exposure. Yet questions still remain about how the virus impacts the health of pregnant women and newborns.

In a new study published in JAMA Network Open, physician-researchers from Beth Israel Deaconess Medical Center (BIDMC), Brigham and Women's Hospital, Boston Children's Hospital and Massachusetts General Hospital reveal that, while mother-to-newborn transmission of the virus is rare, newborns of expectant mothers with COVID-19 can suffer indirect adverse health risks as a result of worsening maternal COVID-19 illness.

"At the start of the pandemic, there was very little data to guide evidence-based newborn care practices," said corresponding author Asimenia Angelidou, MD, PhD, a neonatologist at BIDMC. "We believe ours is the first study to dive into the risk factors for mother-to-newborn SARS-CoV-2 transmission. We expected the mode of delivery and/or the degree of maternal illness to increase the risk of newborn infection, but were surprised to find that this was not the case."

Examining neonatal outcomes during the first month of life for babies born at 11 hospitals that represent approximately 50 percent of all births in Massachusetts, the team identified 255 neonates delivered between March 1 - July 31, 2020, to mothers with a recent positive SARS-CoV-2 test result. The researchers used the American Academy of Pediatrics' National Registry for Surveillance and Epidemiology of Perinatal COVID-19 Infection complemented by a Massachusetts-specific Registry. Out of the 255 neonates studied, 88.2 percent were tested for SARS-CoV-2, and only 2.2 percent had positive results. However, while infection rates among newborns were relatively low, worsening maternal illness accounted for 73.9 percent of preterm births. Premature birth can often lead to acute and chronic complications, including respiratory distress, chronic health problems and developmental disabilities.

"We found that of babies born to mothers with COVID-19, very few babies tested positive," said senior author Mandy Brown Belfort, MD, MPH, Director of Clinical Research in the Department of Pediatric Newborn Medicine at Brigham and Women's Hospital and Associate Professor of Pediatrics at Harvard Medical School. "Instead, the adverse health impact of maternal COVID-19 on the newborn was from preterm delivery, usually prompted by a mother's worsening illness. Our findings support the need for thoughtful and collaborative decision-making around delivery timing in the setting of maternal COVID-19 illness."

Other indicators of adverse infant health outcomes the researchers incorporated in their analysis included low birth weight or very low birth weight, need for delivery room resuscitation, length of hospital stay and healthcare utilization for non-routine visits within a month after discharge.

The team found that short-term adverse outcomes were most closely associated with preterm birth and its consequences, rather than infection of the newborn with the virus. However, newborns of socially vulnerable mothers, as determined using a tool created by the Centers for Disease Control and Prevention using residential zip-codes, were at an increased risk for testing positive. The specific pathways by which social vulnerability might affect mother-to-child transmission of COVID-19 include differential access to care and clinician bias. Discrimination may also be a factor in chronic stress, which can diminish antiviral immune responses.

"This observation that newborns of socially vulnerable mothers were five times more likely to have COVID-19 highlights that health disparities are very complex and extend beyond race, ethnicity and language status," said Angelidou, who is also Instructor in Pediatrics at Harvard Medical School. "Social vulnerability likely affects health and immunity and our study supports further research in this area. Reallocation of resources to socially vulnerable communities could go a long way in decreasing human suffering and economic loss during disease outbreaks."

The authors suggest further research on perinatal viral transmission should include women with COVID-19 early in pregnancy in order to identify the window of highest susceptibility to the virus for mother and baby during pregnancy. Conversely, future research including pregnant women immunized against COVID-19 is important to inform the optimal window for maximal neonatal protection after maternal immunization.

"While the low rates of neonatal infection we observed are reassuring, it is important that providers remain vigilant." said Angelidou, who is also a scientist at the Precision Vaccines Program in the Division of Infectious Diseases at Boston Children's Hospital. "Even during public health emergencies like the ongoing pandemic, providers need to carefully monitor newborns for atypical signs of the illness, while also trying to avoid unnecessary premature deliveries that pose inherent risks for both mother and child."

Paper Title: Safety of Tranexamic Acid in Hip and Knee Arthroplasty in High-risk Patients

Journal: Anesthesiology

Authors: Jashvant Poeran MD, PhD, Director of the Center for Clinical and Outcomes Research, and Associate Professor of Population Health Science & Policy and Orthopedics at the Icahn School of Medicine at Mount Sinai; Calin S. Moucha, MD, Chief of Adult Reconstruction & Joint Replacement Surgery at Mount Sinai Hospital, and Associate Professor of Orthopedics at the Icahn School of Medicine at Mount Sinai; and other coauthors.

Bottom Line: The use of the drug tranexamic acid is commonplace in patients undergoing hip or knee replacement surgery to reduce blood loss. However, this drug works by promoting clotting and safety concerns exist when used in certain high-risk patients such as those with a history of heart attacks, seizures, blood clots, strokes/mini strokes, renal disease, or irregular and rapid heart rates.

Results: Using national data from more than 40,000 patients at 500 hospitals in this retrospective cohort study, Mount Sinai researchers found that approximately half of high-risk patients receive tranexamic acid, similar to non-high-risk patients. Moreover, tranexamic acid use in high-risk patients undergoing hip or knee replacement surgeries is associated with fewer blood transfusions. Most importantly, the researchers found that use of tranexamic acid is not associated with complications such as deep vein blood clots, heart attacks, seizures, or strokes/mini strokes when used in high-risk patients.

Why the Research Is Interesting: The findings address an important knowledge gap on the use of tranexamic acid, a drug that is currently used in the majority of patients undergoing hip and knee replacement surgery. It is unclear how safe this drug is when used in high-risk patients undergoing hip and knee replacement surgery. Mount Sinai's research confirms prior smaller studies that show there is no evidence suggesting the drug carries more complications in high-risk patients.

However, the Mount Sinai team asserts the importance of continued studies to track the safety of tranexamic acid since it has become increasingly used in patients undergoing hip and knee replacement surgeries. Future studies should focus on more detailed parameters on how to reduce the risk of complications in high-risk patients, such as comparing different ways of administering the drug (oral, intravenous, or topical) and dose adjustments.

Who: More than 40,000 patients at 500 U. S. hospitals who underwent hip and knee replacement surgeries.

When: Orthopedic surgeries between 2013 to 2016.

What: The study measured the number of patients who experienced complications following administration of the clotting drug tranexamic acid during hip and knee replacement surgeries.

How: Using the national Premier Healthcare claims database, Mount Sinai researchers analyzed data on patients with preexisting comorbidities who underwent hip and replacement surgeries with use of tranexamic acid. They also considered patient outcomes including a new-onset complication, need for a blood transfusion, and hospital readmission.

Study Conclusions: Tranexamic acid, a decades-old clotting drug that is on the World Health Organization's Essential Medicines list, has been used successfully in various scenarios, including hip and knee replacement surgery, to reduce blood loss and diminish the need for blood transfusions. However, concerns for potential complications persist, especially when the clotting drug is used in high-risk patients. The study did not show an increased risk for complications, and supplements previous smaller studies that confirm the safety of the drug when used in patients undergoing orthopedic surgery.

Said Mount Sinai's Dr. Jashvant Poeran of the research:
This is by no means the final 'say' on this topic, but yet another encouraging sign of the safety of this drug. With an aging population, the demand for such orthopedic surgeries is going to increase and it is, therefore, important to continue study ways to improve patient care and outcomes.

Said Mount Sinai's Dr. Calin S. Moucha of the research:
This is an important clinical conundrum that keeps on coming up as we are aware of the effectiveness of tranexamic acid, but there is not that much data out there on the safety of using tranexamic acid in high-risk patients. Our results will help anesthesiologists and surgeons in their clinical decision-making on something that is unlikely to be answered by a clinical trial.