Culture

A group of Brazilian and Portuguese researchers observed a correlation between the presence of lead in the organism and a microRNA (miRNA) that could be associated with the mechanisms that regulate DNA methylation, a physiological process required to control gene expression and ensure that genes function properly.

The alterations were detected in blood cells from workers in automotive battery plants, which use lead as a raw material. Curiously, lead levels in blood samples from 85 volunteers – averaging 20 micrograms per deciliter of blood (20 µg/dl) – were lower than the acceptable ceiling defined in Brazilian law (60 µg/dl).

The study was supported by FAPESP and reported in an article published in Frontiers in Genetics. The authors are affiliated with the Federal University of São Paulo (UNIFESP), the Federal University of the ABC (UFABC), Anhembi Morumbi University, and the University of São Paulo (USP) in Brazil, and the New University of Lisbon (UNL) in Portugal. The study was part of a project funded by FAPESP.

“What all the studies conducted to date suggest, albeit incipiently, is that low-level exposure to lead isn’t necessarily associated with a lack of adverse effects but may correlate with molecular events that precede the events that are well-established in the literature as deriving from chronic lead poisoning, such as neurological and hematological problems,” said Gustavo Rafael Mazzaron Barcelos, last author of the article. Barcelos is a professor at UNIFESP’s Institute of Health and Society (ISS) in Santos, São Paulo state.

Although low doses did not correlate directly with health problems, he added, the DNA alterations should serve as a warning. “These levels cannot be considered safe. It would be great if lead exposure levels could be minimal, but a whole industrial system depends on production of lead. We need good public policy to minimize exposure, which we’ve been observing systematically in Brazil for decades,” Barcelos said.

In Brazil, any lead exposure exceeding 60 µg/dl must be reported to the SUS, the national health service, and the social security authorities. In China, research has shown that local workers have higher blood lead levels, averaging around 40 µg/dl.

“We analyzed DNA methylation, one of the epigenetic changes that occur mainly in promoter regions, which control gene functions. When methylation in these regions undergoes such changes, protein synthesis may become dysregulated, potentially causing problems. There’s evidence that lead exposure can inhibit DMNT1, the enzyme responsible for controlling DNA methylation. In the samples we analyzed, we found an abundance of miR-148a, a miRNA that targets the gene for DMNT1,” said Marilia Ladeira de Araújo, first author of the article. The study was part of her PhD research at ISS-UNIFESP. She performed part of the analysis while working as a research intern at UNL’s Medical School with a scholarship from FAPESP.

Detection

In a previous study, the group had detected an overall decrease in DNA methylation in the same worker cohort, using samples taken at plants in the state of Paraná. Reported in the Journal of Toxicology and Environmental Health, Part A, the study was part of the master’s research of Paula Pícoli Devóz at the University of São Paulo’s Ribeirão Preto School of Pharmaceutical Sciences (FCFRP-USP). Devóz is also a co-author of the latest published study.

The researchers then decided to look for biomarkers of reduced DNA methylation, identifying several miRNAs that could be associated with this event. They observed a significant increase in miR-148a, noted in the literature as being associated with DNA damage, inflammatory processes, and oxidative stress, all of which may correlate with the development of multifactor pathologies such as neurodegenerative diseases and cancer, for example.

“The advantage of using miR-148a as a biomarker of epigenetic disturbances induced by lead exposure is that these alterations in its expression may precede various cellular disorders, such as oxidative stress and cell death,” Barcelos said. “We don’t yet know whether a decrease in DNA methylation has adverse effects. We analyzed the overall status of this parameter in DNA as a whole, but we now know it’s a potential biomarker of this condition.”

As soon as the pandemic is over, he plans to continue the research by collecting more samples from the same cohort over a relatively long period to see if the effects of low-level exposure persist and how the organism can adapt to it.

The article “Association between miR-148a and DNA methylation profile in individuals exposed to lead (Pb)” is at: www.frontiersin.org/articles/10.3389/fgene.2021.620744/.

Journal

Frontiers in Genetics

DOI

10.3389/fgene.2021.620744

Researchers at the University of California, Davis, have found a link between traffic-related air pollution and an increased risk for age-related dementia, including Alzheimer's disease. Their study, based on rodent models, corroborates previous epidemiological evidence showing this association.

Alzheimer's disease is the most common cause of age-related dementia and the sixth leading cause of death in the United States. More than 5 million Americans currently live with Alzheimer's disease -- a number that is expected to triple by 2050 as the population ages. Health care costs for those patients are predicted to grow from $305 billion in 2020 to $1.1 trillion by 2050.

UC Davis toxicologist Pamela Lein, senior author of the study recently published in Environmental Health Perspectives, said their findings underscore the urgent need to identify factors that contribute to the onset and progression of Alzheimer's to develop effective preventive measures for reducing the individual and societal burden of this disease.

Lein worked with UC Davis atmospheric scientist Anthony Wexler and first author Kelley Patten, while she was a doctoral student in the UC Davis graduate group for pharmacology and toxicology, to develop a novel approach to study the impacts of traffic-related air pollution in real time. Researchers set up a rodent vivarium near a traffic tunnel in Northern California so they could mimic, as closely as possible, what humans might experience from traffic-related air pollution.

"This approach was a creative way to get at the question of what impacts air pollution has on the brain in the absence of confounding factors such as socioeconomic influences, diet, etc.," Lein said. "It's important to know if living close to these roadways poses a significant risk to the human brain as it ages."

Exposure outcomes on the aging brain

The researchers exposed male and female rats for up to 14 months to filtered air or polluted air drawn from the tunnel and delivered it to animals unchanged in real time. The subjects were divided into two groups: wild type rats and those that express Alzheimer's disease risk genes that are relevant to humans.

Testing was conducted in 3-, 6-, 10- and 15-month-old animals using hyperspectral imaging, behavioral testing and neuropathologic measures to quantify the expression of Alzheimer's disease characteristics.

"We saw that traffic-related air pollution accelerated Alzheimer's disease characteristics not only in the animals who express the risk gene (which we anticipated) but also in the wild type rats," Lein said. "We didn't anticipate that. The big, exciting discovery is that traffic-related air pollution is a risk factor for late-onset Alzheimer's disease. This is important because this pollution is everywhere and could explain the increased number of people impacted by Alzheimer's disease across the world."

What remains unclear is which component of that pollution is predominately responsible for the effects on the brain. There are gases, particulate matter, road dust, tire wear, vibration and noise involved in traffic-related air pollution.

"The next set of studies is to try and tease apart specific components of traffic-related air pollution that drive these Alzheimer's disease traits," Lein said. "Or is it the collective mix that causes the damage?"

Fine particles (PM 2.5) in the polluted air at the study site were below federal regulatory limits, but ultrafine particles, which are not regulated, were detected in the brains of exposed animals.

"The Environmental Protection Agency only regulates down to the PM 2.5 level, but the bulk of this traffic-related air pollution is ultrafine particulate matter," Lein said. "These studies provide incentive to re-evaluate the current regulatory standards and suggest that current ones are not protective of the aging brain."

The study shows traffic-related air pollution can deliver a double whammy, decreasing the time of onset of Alzheimer's disease characteristics and accelerating disease progression. While personal factors can change an individual's risk for Alzheimer's disease (exercise, smoking, diet), people are often poor about sticking to a plan to decrease their risk factors.

"There's a lot of data that shows if you can regulate risk factors through policy at a population level, you have a more significant public health impact than if you try to regulate them at the individual level," Lein said. "If we could make some progress in identifying which component in traffic-related air pollution is causing these effects, then scientists can approach legislators to develop scientifically based regulations. Even if we can delay onset of Alzheimer's disease by five years, we could potentially save our health care system an enormous amount of money."

This study is one of four published papers to come out of the research site to date. A prior study, published in Translational Psychiatry focused on the developing brain and found a link between traffic-related air pollution and an increased risk for changes in brain development relevant to neurodevelopmental disorders such as autism.

In patients receiving therapeutic hypothermia after suffering out-of-hospital cardiac arrest, those who were cooled below 31 degrees Celsius (about 88 degrees Fahrenheit) for 24 hours showed no difference in terms of death or poor neurological outcomes at six months compared with patients receiving guideline-recommended cooling of 34 C (about 93 F). These findings are part of a study presented at the American College of Cardiology's 70th Annual Scientific Session.

Therapeutic hypothermia is a procedure in which a person's body is cooled far below normal body temperature. It has been shown to improve survival and reduce brain damage in people who have been resuscitated but remain comatose after suffering cardiac arrest (when the heart stops pumping effectively). Current guidelines for therapeutic hypothermia recommend cooling the body to 32-36 C for 24 hours. The new study found no benefit from a deeper cooling to 31 C.

"The results of our trial do not support the use of moderate therapeutic hypothermia of 31 C to improve neurological outcomes in comatose survivors of out-of-hospital cardiac arrest," said Michel R. Le May, MD, interventional cardiologist at the University of Ottawa Heart Institute and the study's lead author. "These findings do not support changing the current guidelines; we need to look for other strategies that can improve outcomes for these patients who currently have a poor prognosis."

The trial enrolled 367 patients treated for out-of-hospital cardiac arrest at the University of Ottawa Heart Institute between 2013-2020. All patients had been successfully resuscitated, as indicated by a return of blood pressure, but remained comatose. Participants were cooled with an endovascular device that uses temperature-controlled saline-filled balloons inserted near the heart via a vein to alter a patient's body temperature. For half of the patients, the endovascular device was set to cool the body to 31 C and for the other half the device was set to 34 C. Once the target temperature was achieved, the temperature was maintained for 24 hours before the patient was warmed up to normal body temperature at a rate of 0.25 degrees per hour.

The trial is the first to use a randomized, double-blind approach for testing different target temperatures for therapeutic hypothermia. Physicians overseeing the treatment were prevented from seeing the temperature setting by a shield placed over the temperature display on the endovascular machine. Nurses were aware of the temperatures but maintained separate charts to maintain blinding among the treating physicians.

The study's primary endpoint, a composite of death or poor neurological outcome at six months, occurred in 48% of those cooled to 31 C and 45% of those cooled to 34 C, a difference that was not statistically significant. There was also no significant difference between groups in terms of the rate of death or the rate of poor neurological outcome when these outcomes were assessed individually. The researchers examined outcomes by sex, age and other variables but found no significant differences in any subgroups analyzed.

Patients cooled to 31 C on average had a longer stay in the cardiac intensive care unit, which Le May said may reflect the fact that both the cool-down and warm-up periods lasted longer for these patients due to the lower target temperature.

Other researchers have assessed whether different temperatures or durations of therapeutic hypothermia can improve outcomes, but these previous studies have similarly demonstrated no improvement over current guidelines. Moving forward, Le May suggested brain monitoring approaches could be used to inform which strategies may be best suited for each patient's particular situation.

"It may be useful to pool all these studies together and try to figure out if there is a particular temperature that's more suitable in particular cases," Le May said. "We also have to find better, noninvasive tools to assess the brain and perhaps turn our attention toward a more personalized way of treating these patients. This would allow us to select the protocol that optimizes the benefit for a particular patient."

Le May said that many key elements influencing survival after out-of-hospital cardiac arrest come into play before the patient reaches the hospital, including whether bystanders administer basic CPR, how quickly paramedics arrive on the scene and how quickly patients are transferred to specialized cardiac centers. Focusing on these factors could offer opportunities to further improve survival, he said.

The study was conducted at a single center, which may limit its generalizability but was helpful in ensuring consistent treatment protocols, Le May said.

Patients with chronic kidney disease and Type 2 diabetes who took the experimental drug finerenone were about 30% less likely to develop the heart rhythm disorder atrial fibrillation (AFib) than those taking a placebo, according to data presented at the American College of Cardiology's 70th Annual Scientific Session.

Last year, researchers reported that the trial, called FIDELIO-DKD, met its primary endpoint showing a significant benefit of finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, in terms of a composite of sustained decrease in kidney function, kidney failure and renal death. The new analysis reveals that patients derived these benefits regardless of their history with AFib and suggests that taking finerenone also reduced the rate of new-onset AFib.

"Finerenone can lower the risk of development of atrial fibrillation in patients with chronic kidney disease and diabetes and can be used as a therapeutic strategy to delay its onset," said Gerasimos Filippatos, MD, from the National and Kapodistrian University of Athens, School of Medicine, Attikon University Hospital in Athens, Greece, and the study's lead author. "It can also protect the heart and the kidney from further damage caused by chronic kidney disease and diabetes in these patients with or without pre-existing atrial fibrillation."

Chronic kidney disease, diabetes and AFib are major public health concerns worldwide. Patients with chronic kidney disease and diabetes face an increased risk of developing AFib because these conditions can cause changes in the heart's structure and electric signaling, leading to fast and erratic heart rhythms. During preclinical studies, finerenone was reported to slow these structural changes.

FIDELIO-DKD randomly assigned 5,674 patients with chronic kidney disease and diabetes to take finerenone or a placebo and tracked outcomes for a median of 2.6 years. The primary endpoint was a composite of kidney failure, renal death or sustained decrease in estimated glomerular filtration rate (a measure of kidney function) of 40% or more from baseline. The key secondary outcome included death by loss of heart function, nonfatal heart attack, nonfatal stroke or hospitalization for heart failure.

As previously reported, finerenone significantly lowered the risk of kidney events by 18% and the risk of cardiovascular events by 14% compared with placebo. For the new analysis, researchers assessed outcomes among patients with and without a history of AFib or atrial flutter (about 8% of participants had AFib or atrial flutter at the start of the trial) and the risk of patients developing AFib or atrial flutter during the study.

The results found the primary and secondary endpoints were significantly lower in patients taking finerenone regardless of their AFib status at the start of the study.

"The previously-reported kidney and heart protection with finerenone applied equally to patients with and without pre-existing atrial fibrillation," Filippatos said.

In addition, new-onset AFib or atrial flutter was reported in 3.2% of patients taking finerenone and 4.5% of those taking a placebo, a significant difference in favor of finerenone.

Researchers said that previous findings from preclinical studies have suggested that finerenone may help reduce scarring and thickening of the heart tissue, possibly through its action of blocking mineralocorticoid receptors, a type of protein molecule present on many cell types in the heart and kidney that has been shown to be especially abundant in patients with AFib.

"Preventing or delaying the onset of atrial fibrillation in patients with chronic kidney disease and diabetes is particularly important since having atrial fibrillation can worsen chronic kidney disease and having diabetes can worsen atrial fibrillation symptoms," Filippatos said. "Treatment in these patients can also be challenging because they are prone to developing blood clots [which can lead to stroke] and bleeding. Finerenone has the potential to reduce the burden of atrial fibrillation in these patients."

Filippatos said that larger studies focused specifically on new-onset AFib would be needed to confirm the findings. Because participants underwent heart rhythm tests only once per year in FIDELIO-DKD, Filippatos said it is possible that researchers missed asymptomatic AFib or cases that were not apparent from tests. A separate trial is currently underway to examine finerenone's effects in patients with less severe chronic kidney disease and diabetes.

A subgroup of patients who experienced an out-of-hospital cardiac arrest (OHCA) that did not respond to standard advanced cardiac life support (ACLS), were immediately transported to a cardiac care center, and placed on a device similar to a heart-lung bypass machine were more likely to have survived with good brain function six months later than similar patients who received standard care at the site where the OHCA occurred. The study was presented at the American College of Cardiology's 70th Annual Scientific Session.

"This study--the largest randomized clinical trial that has been conducted to address this question--shows that a hyperinvasive approach is a feasible and effective treatment strategy for OHCA," said Jan Blohlávek, MD, PhD, professor of medicine at Charles University in Prague, Czech Republic, and lead author of the study.

Although the primary endpoint (six-month survival with good brain function as assessed by a validated scale for measuring cerebral performance after a cardiac arrest) was not met, the trial was stopped prematurely because the hyperinvasive approach showed efficacy in subgroups of patients.

Cardiac arrest occurs when a sudden malfunction of the heart's electrical system causes the heart to begin beating very erratically, which interrupts blood flow to the heart and brain. According to the Centers for Disease Control and Prevention, about 375,000 people have an OHCA every year in the U.S. The survival rate after an OHCA is about 12%. To survive, the patient must receive immediate cardiopulmonary resuscitation (CPR) to increase blood flow to the heart and brain and an electrical shock from a defibrillator to stop the abnormal heart rhythm.

The study involved 256 patients who experienced a witnessed OHCA. The patients' median age was 57 years and 92% were men. About 45% had high blood pressure and 20% had a history of coronary artery disease. They were randomly assigned to receive either standard advanced cardiac life support or hyperinvasive support.

Patients in the standard-care group (the S group) were treated at the site where the OHCA occurred with manual CPR, defibrillation, medications to reverse the cardiac arrest and other elements of usual care for a cardiac arrest. Patients in the hyperinvasive group (the H group) received mechanical CPR using a device that provided automatic chest compression and were transported immediately to a cardiac center where--if their heartbeat was not restarted en route--they were placed on an extracorporeal membrane oxygenation (ECMO) machine. This machine temporarily takes over the work of the heart and lungs by infusing fresh oxygen into the blood and pumping blood to the body's organs and tissues.

After six months, 31.5% of patients in the H group and 22% of those in the S group had survived with good brain function, a difference that was not statistically significant. As secondary outcomes, Blohlávek and his colleagues looked at the proportion of patients in each group who had recovered neurological and cardiac function at 30 days after the OHCA. In the H group, 34.7% had good neurological function at 30 days, compared with 22.7% in the S group, a statistically significant difference. Recovery of cardiac function was similar in the two groups.

The main benefit of the hyperinvasive approach was evident in a subgroup of patients who were resuscitated for more than 45 minutes; 20 patients in the H group survived, compared with six in the S group. Moreover, four of the six survivors in the S group had been crossed over to the H group and had therefore received hyperinvasive rather than standard treatment.

The study design allowed emergency medical staff at the scene and at the hospital to switch (or "crossover") patients randomly assigned to the S group to the H group or vice versa. Patients assigned to the H group could be switched to the S group if hyperinvasive intervention would likely be futile. The overall crossover was low; of the 256 patients enrolled in the study, 11 (8.3%) randomly assigned to the S group were switched to the H group, while nine (7.2%) randomly assigned to the H group were switched to the S group. However, because the study used a rigorous form of analysis known as "intention to treat," patients who crossed over were still counted as part of the group they had been randomly assigned. According to Blohlávek, in patients who crossed over from the S group to the H group, 40% survived with normal neurological outcomes, while none of the patients survived in a switch from the H group to the S group.

The study's data safety and monitoring board--an independent group of experts whose job was to review the study data at prespecified intervals--decided to stop the study after 256 subjects had been enrolled, when it became clear that survival and neurological recovery were superior in the H group, Blohlávek said. For this reason, the study did not reach its prespecified enrollment target of 570 patients.

Patient survival in the S group, at 22%, was more than twice as high as the researchers had expected. "A byproduct of training the emergency medical teams to conduct the hyperinvasive protocol is that they also achieved extraordinarily good results among patients who received standard [advanced cardiac life support]," Blohlávek said.

The study has implications for practice, based on the findings that the hyperinvasive approach was most beneficial for patients who were resuscitated for more than 45 minutes and that, among patients who were resuscitated for a shorter time, the number of neurologically intact survivors was similar in both groups, Blohlávek said.

"Timely transport to a hospital and treatment with ECMO should be considered for patients whose hearts do not regain spontaneous activity with standard advanced cardiac life support," Blohlávek said. "However, this may be viable only in circumstances where there is absolutely optimal prehospital care, including the ability to have a bystander perform chest compressions at the scene of the arrest with direction via telephone from the emergency dispatch center, and the ability to quickly transport the patient to a dedicated cardiac center where highly trained specialists are available."

The ocean is a big place with many deep, dark mysteries. Humans have mapped no more than 20% of the sea, and explored less. Even the kelp forests of Southern California -- among the best studied patches of ocean on the planet -- hide species not yet described by science.

Now, UC Santa Barbara's Thomas Turner has published a paper in the journal Zootaxa describing four new species of sponges. These novel specimens weren't dredged from the murky depths or found on some distant seamount, but collected locally from popular dive spots. The study brings Turner's new species count to five, and the scientist believes there may be dozens yet to discover and describe along the West Coast.

Turner, an associate professor in the Department of Ecology, Evolution, and Marine Biology, collected hundreds of samples by hand from dives he conducted all around Southern California. He made sure to photograph each sponge in its natural habitat, documentation that will provide a wealth of information not otherwise available once a specimen goes into a collection. Back in the lab, he got to work analyzing their anatomy and sequencing their genes.

In 2020, Turner described his first new species of sponge using these molecular techniques: Galaxia gaviotensis, which he found just west of Santa Barbara. He suggested the common name Gaviota galaxy sponge. "Like a galaxy, the type species of the genus is packed with a diversity of stars," he wrote, referring to the shape of its spicules, microscopic objects that provide structural support to many sponges.

The four species in the new paper appear to a layperson as nondescript beige patches on kelp forest rocks. At first, Turner couldn't even tell what order they belonged to. But while the simple creatures can be hard to distinguish visually, their genomes can reveal their differences. So this is where Turner focused his efforts.

"When I got the DNA, and I was shocked to learn that they were in Scopolinida, which is almost entirely tropical," he said. Species in this order were unknown from the west coast. In fact, no one had documented Scopolinid sponges anywhere in the eastern Pacific.

And laypeople have certainly come across at least two of these species. "They live out in the open; divers have been swimming past them for decades," Turner said. He even found pictures of one of them on the citizen science app iNaturalist. "They're all over Southern California, super common. Just no scientist has ever picked one up and looked at it to try to figure out what it was."

When naming a new species, a scientist often try to highlight a salient characteristic of the organism. This is challenging to do for a bunch of beige splotches. So Turner named two after the locations where he found them: S. goletensis, for the town of Goleta; and S. kuyamu, for the village of Kuyamu, a community of Barbareño Chumash that once stood onshore at the site where the sponge was discovered. Based on their genomics, Turner concluded that these two are sister species, more closely related to each other than any other known sponges.

Turner coined the name S. jali for the third species after the patterns on its surface, which reminded him of a jali, a latticed screen common in Indo-Islamic architecture. He named the final species after Nausicaä, a character in the Hayao Miyazaki film "Nausicaä of the Valley of the Wind." The film is about humans and nature, he explained, and a lot of the weird organisms in the fictional world filter and clean the environment like a sponge. In fact, sponges are unique in consuming even viruses and bacteria, he added; many other filter feeders forgo these minute morsels in favor of much larger plankton.

Sponges diverged from all other animals over 600 million years ago, with the major subgroups parting ways not long after that. "So, the amount of independent evolution within sponges is comparable to that within all other animals," explained Turner. Because they diverged from other animals so long ago, they can potentially tell scientists a lot about our origins.

The animals have also caught the attention of biomedical researchers. Given how porous they are, sponges are much more intertwined with their external environment than any other animal. As a result, they have to actively manage their bacterial and viral loads. This has led sponges and their microbiota to produce a lot of antimicrobial and even anti-cancer compounds, Turner said.

Despite their long evolutionary history, most sponges have retained similarities like a simple body plan and filter-feeding lifestyle. Sponges' simplicity and similarity has long vexed scientists, who used to classify life based on morphology: the form and function of organisms. "For basically 200 years, taxonomists have struggled to figure out how to classify the sponges because they offer so few morphological characteristics," Turner remarked.

Only in the past few decades have researchers straightened out the different orders of sponges. "A taxonomic order is a pretty big group of animals," Turner continued. "For example, cats, dogs and walruses are all in the same order: Carnivora."

Taxonomy is never carried out just for taxonomists. It's done to lay a foundation for researchers in other fields to build upon. "Trying to conduct research without taxonomy is kind of like if you went to the Library of Congress and there weren't any librarians, and all the books were just in a big pile," Turner said. "There's plenty of information there, but you can't do anything with it. The taxonomist's job is the librarian's job: to organize all that information so that everyone else can study it."

Ecologists are often at a loss when it comes to sponges, Turner explained, simply because the taxonomy and systematics haven't been done to figure out what's what. That's the situation that greeted Turner when sponges first caught his interest a few years ago.

"I was diving recreationally in the kelp forest here, and I was seeing all these sponges," he recalled. "I couldn't tell what they were; I didn't know what was important to them; I couldn't tell what was different from one to another; and I was getting really frustrated." Finally, he decided that someone needed to straighten this out, and it might as well be him.

Turner's experience as a scientific diver combined with his background in genomics made him perfectly suited to begin sorting out the taxonomy and systematics of West Coast sponges. Since 2018 he has collected about 800 specimens. The four species in this paper, plus the one from 2020, are just the beginning of his work describing perhaps 100 new species and adding critical information to hundreds of others.

DNA sequencing offers a path forward to understanding these animals, but there's still a lot of painstaking morphological analysis in Turner's future. That's because, by combining these two methodologies, he can bridge the gap between modern molecular biology and our historical reliance on physiology. "That is the only way out of this morass that we're in regarding sponge taxonomy," Turner said, "combining the morphology with the genetics."

Unfortunately, many sponge specimens were preserved in ways that did not safeguard the animals' DNA. This will make it a challenge to bring old collections into the era of molecular biology. In that light, Turner is applying for funding to investigate how to extract DNA from old sponge samples.

As perhaps the only sponge taxonomist on the U.S. Pacific coast, Turner also intends to continue his research on the region's sponges. He plans to start sequencing the whole genomes of sponges he's collected, looking for patterns of molecular evolution to try and sort out what makes one different from another, and what that can tell us about their ecology and evolution. His research is supported by The Southern California Bight Marine Biodiversity Observation Network (SCB MBON), a long-term collaboration led by UC Santa Barbara's Robert Miller. The results should elucidate the roles these animals play in their ecosystems.

"It's all about building a foundation that lots of other people can hopefully build upon," he said, "and establishing a new direction for marine study in California wherein people can use sponges in their research."

Alcohol appears to have an immediate--or near-immediate--effect on heart rhythm, significantly increasing the chance that an episode of atrial fibrillation (AFib) will occur, according to new data presented at the American College of Cardiology's 70th Annual Scientific Session.

The data revealed that just one glass of wine, beer or other alcoholic beverage was associated with twofold greater odds of an episode of AFib occurring within the next four hours. Among people having two or more drinks in one sitting, there was a more than threefold higher chance of experiencing AFib. Using an alcohol sensor placed on participants' ankles, which passively monitored alcohol intake, the investigators found that every 0.1% increase in inferred blood alcohol concentration over the previous 12 hours was associated with an approximate 40% higher odds of an AFib episode. Evidence from those sensors also demonstrated that the total alcohol concentration over time also predicted the chance AFib would occur.

"Alcohol is the most commonly consumed drug in the world, and there is still a lot we don't understand about what it does to our bodies and, in particular, our hearts," said Gregory M. Marcus, MD, cardiologist and professor of medicine at the University of California, San Francisco, and the study's lead author. "Based on our data, we found that alcohol can acutely influence the likelihood that an episode of AFib will occur within a few hours, and the more alcohol consumed, the higher the risk of having an event."

AFib is the most common heart rhythm disorder. It is often characterized by a rapid, chaotic and fluttery heartbeat. Marcus said that people can experience a range of symptoms. Some may not feel anything, while others are overcome with severe shortness of breath, fatigue, fainting or near fainting spells and a disconcerting sensation that the heart is beating out of control. AFib also results in costly use of health care services, including visits to the emergency department, hospitalizations and procedures each year. Over time, AFib can lead to heart failure, stroke and dementia if untreated.

Researchers enrolled 100 patients with paroxysmal or intermittent AFib, which tends to go away within a short period of time (unlike chronic AFib). Patients in the study were 64 years old on average; the majority were white (85%) or male (80%). Past medical history, medications and lifestyle habits were assessed through chart reviews and patient interviews. Each participant was fitted with a wearable heart monitor that continuously tracked their heart rhythm and an ankle sensor to objectively detect when more than two to three drinks were consumed on a given occasion. Participants were asked to press a button on the heart monitor each time they had an alcoholic drink. Finger stick blood tests measuring alcohol consumption in the previous few weeks were also used to corroborate self-reported drinking events. Because researchers used repeated measurements from the same individual, they served as their own control over time. Overall, more than half (56) had an episode of AFib during the four-week study.

"Patients have been telling us that alcohol is a trigger for AFib for a long time, but it's been hard, if not impossible, to study because there is a critical temporal relationship that requires a real-time assessment of alcohol intake and heart rhythm," Marcus said. "This is the first study to objectively demonstrate and quantify the real-time relationship between alcohol consumption and AFib episodes. While this study was limited to people with intermittent AFib, it's reasonable to extrapolate the fact that in many people alcohol may be the main trigger for an initial episode."

Marcus said there may be other factors--such as race/ethnicity, sex, genetics or other environmental exposures--that influence alcohol's effect on the heart in various ways and need to be studied. In addition, people often pair alcohol with foods that are high in sodium, while some pour a drink because they feel stressed, so there may be other things that play a role. The findings also run counter to previous reports about the potentially protective role of alcohol on heart health when used in moderation.

"There is conventional wisdom that alcohol is 'good' or 'healthy' for the heart, based on observational studies, but that relates to coronary heart disease and heart attack. These new data present an interesting conundrum regarding the overall risks versus benefits of alcohol in moderation," Marcus said. "But the data is very clear that more is not better when it comes to alcohol; those who drink more have a higher risk of heart attack and death."

Marcus added that this situation is a perfect example where precision medicine may play a clinically relevant role to help identify which patients are at high risk for alcohol-related AFib. Those who are not at high-risk of the harmful effects of alcohol might yet benefit from moderate alcohol consumption as another way to potentially protect them from coronary blockages and disease.

The general recommendation for daily alcohol consumption is no more than one standard alcoholic beverage a day for women and two for men.

"Still, when patients ask me what they can do to avoid an AFib episode, I tell them the evidence suggests that they should minimize, if not completely eliminate, alcohol. But we have to consider quality of life as well, which is both relevant to arrhythmia symptoms and the opportunity to enjoy a glass of wine once in a while for some. So, it's not as simple as instructing everyone to avoid alcohol," Marcus said.

As far as next steps, Marcus and his team will look at how these results, which are limited to those with intermittent AFib, may apply to the general population. They also hope to identify other factors that may influence the relationship between alcohol and AFib, including genetics.

The study was funded by the National Institute on Alcohol Abuse and Alcoholism.

Marcus will be available to the media in a virtual press conference on Monday, May 17, at 12:15 p.m. ET/ 16:15 UTC.

Marcus will present the study, "Acute Alcohol Consumption and Discrete Atrial Fibrillation Events," on Monday, May 17, at 10:45 a.m. ET / 14:45 UTC, virtually.

On Sept. 9, 2018, astronomers spotted a flash from a galaxy 860 million light years away. The source was a supermassive black hole about 50 million times the mass of the sun. Normally quiet, the gravitational giant suddenly awoke to devour a passing star in a rare instance known as a tidal disruption event. As the stellar debris fell toward the black hole, it released an enormous amount of energy in the form of light.

Researchers at MIT, the European Southern Observatory, and elsewhere used multiple telescopes to keep watch on the event, labeled AT2018fyk. To their surprise, they observed that as the supermassive black hole consumed the star, it exhibited properties that were similar to that of much smaller, stellar-mass black holes.

The results, published today in the Astrophysical Journal, suggest that accretion, or the way black holes evolve as they consume material, is independent of their size.

"We've demonstrated that, if you've seen one black hole, you've seen them all, in a sense," says study author Dheeraj "DJ" Pasham, a research scientist in MIT's Kavli Institute for Astrophysics and Space Research. "When you throw a ball of gas at them, they all seem to do more or less the same thing. They're the same beast in terms of their accretion."

Pasham's co-authors include principal research scientist Ronald Remillard and former graduate student Anirudh Chiti at MIT, along with researchers at the European Southern Observatory, Cambridge University, Leiden University, New York University, the University of Maryland, Curtin University, the University of Amsterdam, and the NASA Goddard Space Flight Center.

A stellar wake-up

When small stellar-mass black holes with a mass about 10 times our sun emit a burst of light, it's often in response to an influx of material from a companion star. This outburst of radiation sets off a specific evolution of the region around the black hole. From quiescence, a black hole transitions into a "soft" phase dominated by an accretion disk as stellar material is pulled into the black hole. As the amount of material influx drops, it transitions again to a "hard" phase where a white-hot corona takes over. The black hole eventually settles back into a steady quiescence, and this entire accretion cycle can last a few weeks to months.

Physicists have observed this characteristic accretion cycle in multiple stellar-mass black holes for several decades. But for supermassive black holes, it was thought that this process would take too long to capture entirely, as these goliaths are normally grazers, feeding slowly on gas in the central regions of a galaxy.

"This process normally happens on timescales of thousands of years in supermassive black holes," Pasham says. "Humans cannot wait that long to capture something like this."

But this entire process speeds up when a black hole experiences a sudden, huge influx of material, such as during a tidal disruption event, when a star comes close enough that a black hole can tidally rip it to shreds.

"In a tidal disruption event, everything is abrupt," Pasham says. "You have a sudden chunk of gas being thrown at you, and the black hole is suddenly woken up, and it's like, 'whoa, there's so much food -- let me just eat, eat, eat until it's gone.' So, it experiences everything in a short timespan. That allows us to probe all these different accretion stages that people have known in stellar-mass black holes."

A supermassive cycle

In September 2018, the All-Sky Automated Survey for Supernovae (ASASSN) picked up signals of a sudden flare. Scientists subsequently determined that the flare was the result of a tidal disruption event involving a supermassive black hole, which they labeled TDE AT2018fyk. Wevers, Pasham, and their colleagues jumped at the alert and were able to steer multiple telescopes, each trained to map different bands of the ultraviolet and X-ray spectrum, toward the system.

The team collected data over two years, using X-ray space telescopes XMM-Newton and the Chandra X-Ray Observatory, as well as NICER, the X-ray-monitoring instrument aboard the International Space Station, and the Swift Observatory, along with radio telescopes in Australia.

"We caught the black hole in the soft state with an accretion disk forming, and most of the emission in ultraviolet, with very few in the X-ray," Pasham says. "Then the disk collapses, the corona gets stronger, and now it's very bright in X-rays. Eventually there's not much gas to feed on, and the overall luminosity drops and goes back to undetectable levels."

The researchers estimate that the black hole tidally disrupted a star about the size of our sun. In the process, it generated an enormous accretion disk, about 12 billion kilometers wide, and emitted gas that they estimated to be about 40,000 Kelvin, or more than 70,000 degrees Fahrenheit. As the disk became weaker and less bright, a corona of compact, high-energy X-rays took over as the dominant phase around the black hole before eventually fading away.

"People have known this cycle to happen in stellar-mass black holes, which are only about 10 solar masses. Now we are seeing this in something 5 million times bigger," Pasham says.

"The most exciting prospect for the future is that such tidal disruption events provide a window into the formation of complex structures very close to the supermassive black hole such as the accretion disk and the corona," says lead author Thomas Wevers, a fellow at the European Southern Observatory. "Studying how these structures form and interact in the extreme environment following the destruction of a star, we can hopefully start to better understand the fundamental physical laws that govern their existence."

In addition to showing that black holes experience accretion in the same way, regardless of their size, the results represent only the second time that scientists have captured the formation of a corona from beginning to end.

"A corona is a very mysterious entity, and in the case of supermassive black holes, people have studied established coronas but don't know when or how they formed," Pasham says. "We've demonstrated you can use tidal disruption events to capture corona formation. I'm excited about using these events in the future to figure out what exactly is the corona."

Indigenous peoples in Canada have higher rates of death and complications after surgery and lower rates of surgeries than other populations, found new research published in CMAJ (Canadian Medical Association Journal).

"Understanding surgical outcomes and access to surgical services is a vital step toward addressing colonialism and structural racism within health care, so we can identify the gaps and determine what needs to be improved," said Dr. Nadine Caron, a general surgeon in Prince George and co-director of the Centre for Excellence in Indigenous Health at the University of British Columbia.

Access to safe and timely surgery is essential, as surgery is responsible for 65% of cancer cure and control, can prevent death following trauma and, in the case of cesarean births, reduces newborn deaths by up to 70%.

Researchers looked at 28 studies that compared surgical outcomes across a range of procedures in Indigenous Peoples to outcomes in non-Indigenous peoples in Canada. Combined, the studies included 1.9 million patients, of whom 10.2% (202,056) identified as Indigenous, although few specifically addressed Inuit or Métis populations.

The research team found Indigenous Peoples had higher rates of complications after surgery; were less likely to undergo life-saving surgery, including cardiac surgery and cesarean deliveries; and experienced longer wait times for kidney transplants. Four studies indicated that Indigenous Peoples had a 30% increased risk of death after surgery and were less likely to undergo surgeries such as joint replacements that improve quality of life.

These findings are consistent with those for Indigenous Peoples in other high-income countries. As the Canadian data were limited and of poor quality, the research team calls for more research and consistent data collection methods.

"This study tells Canadians two things. We need better data, and the data we have tell us that we need to do better," said Dr. Jason McVicar, a Métis anesthesiologist at The Ottawa Hospital, assistant professor at the University of Ottawa and the lead author of the study. He added, "Better-quality research by Indigenous investigators and real-time outcome monitoring for Indigenous patients are essential to eliminating structural racism in the health care system."

The research team has concerns about the effect of the COVID-19 pandemic on access to surgery for Indigenous Peoples. "The pandemic has exposed societal disparities and disproportionately affected vulnerable populations," says Dr. Donna May Kimmaliardjuk, a cardiac surgeon and fellow at The Cleveland Clinic. "This research illuminates the inequities built into our surgical systems. When we begin to address the backlog, those with the political agency to strongly advocate for themselves will inevitably get to the front of the line, which will again disproportionately impact First Nations, Inuit and Métis communities."

Whether it's plankton exposed to parasites or people exposed to pathogens, a host's initial immune response plays an integral role in determining whether infection occurs and to what degree it spreads within a population, new University of Colorado Boulder research suggests.

The findings, published May 13 in The American Naturalist, provide valuable insight for understanding and preventing the transmission of disease within and between animal species. From parasitic flatworms transmitted by snails into humans in developing nations, to zoonotic spillover events from mammals and insects to humans--which have caused global pandemics like COVID-19 and West Nile virus--an infected creature's immune response is a vital variable to consider in calculating what happens next.

"One of the biggest patterns that we're seeing in disease ecology and epidemiology is the fact that not all hosts are equal," said Tara Stewart Merrill, lead author of the paper and a postdoctoral fellow in ecology. "In infectious disease research, we want to build host immunity into our understanding of how disease spreads."

Invertebrates are common vectors for disease, which means they can transmit infectious pathogens between humans or from animals to humans. Vector-borne diseases, like malaria, account for almost 20% of all infectious diseases worldwide and are responsible for more than 700,000 deaths each year.

Yet epidemiological studies have rarely considered invertebrate immunity and recovery in creatures that are vectors for human disease. They assume that once exposed to a pathogen, the invertebrate host will become infected.

But what if it was possible for invertebrates to fight off these diseases, and break the link in the chain that passes them on to humans?

While observing a tiny species of zooplankton (Daphnia dentifera) throughout its lifecycle and exposure to a fungal parasite (Metschnikowia bicuspidata), the researchers saw this potential in action. Some of the plankton were good at stopping fungal spores from entering their bodies, and others cleared the infection within a limited window of time after ingesting the spores.

"Our results show that there are several defenses that invertebrates can use to reduce the likelihood of infection, and that we really need to understand those immune defenses to understand infection patterns," said Stewart Merrill.

Unexpected recovery

Stewart Merrill started this work in her first year as a doctoral student at the University of Illinois, studying this little plankton and its collection of defenses. It's a gruesome process if the plankton fails to ward off the parasite: Its fungal spores attack the plankton's gut, fill its body and grow until they are released when the host finally dies.

But she noticed something that had not been recorded before: Some of the doomed plankton recovered. Several years later, she has found that when faced with identical levels of exposure, the success or failure of these infections depends on the strength of the host's internal defenses during this early limited window of opportunity.

Based on their observations of these individual outcomes, the researchers developed a simple probabilistic model for measuring host immunity that can be applied across wildlife systems, with important applications for diseases transmitted to humans by invertebrates.

"When immune responses are good, they act as a filter that reduces transmission," said Stewart Merrill. "But any environmental change that degrades immunity can actually amplify transmission, because it will let all of that exposure go through and ultimately become infectious."

It's a model that can also apply to COVID-19, as research from CU Boulder has shown that not all hosts are the same in transmitting the coronavirus, and exposure does not directly determine infection.

COVID-19 is also believed to be the result of a zoonotic spillover, an infection that moved from animals into people, and similar probabilistic models could be advantageous in predicting the occurrence and spread of future spillover events, said Stewart Merrill.

Understanding prevention of infection

Stewart Merrill hopes that a better understanding of infections in a simple animal like plankton can be applied more broadly to invertebrates that matter for human health.

In Africa, Southeast Asia, as well as South and Central America, 200 million people suffer from infections caused by schistosomes--invertebrates more commonly known as parasitic flatworms. They cause illness and death, and significant economic and public health consequences, so much so that the World Health Organization considers them the second-most socioeconomically devastating parasitic disease after malaria.

They're just one of many neglected tropical diseases transmitted to people by invertebrate hosts such as snails, mosquitoes and biting flies. These diseases infect a large portion of a population but occur in areas with low levels of sanitation that don't have the economic resources to address those diseases, said Stewart Merrill.

Schistosomes live in freshwater environments that people use for their drinking water, laundry and bathing. So even though there are treatments, the next day a person can easily get reinfected just by accessing the water they need. By better understanding how the flatworms themselves succumb to or fight off infection, scientists like Stewart Merrill help us get closer to stopping the chain of transmission into humans.

"We really need to work on understanding prevention of infection, and what that risk is in those aquatic systems, rather than just cures for infection," she said.

The good news is we can learn from the same invertebrates which infect us. In invertebrate hosts that suffer or die from their infections, there is a good incentive to learn how to build an immune response and fight it off. Some snails have even shown the ability to retain an immunological memory: If they get infected once and survive, then they might never get infected again.

"If we can better understand how the environment shapes those defenses, we could predict into the future how environmental changes might amplify or suppress risk of transmission to people," said Stewart Merrill.

A team including Northwestern University astrophysicists has developed the most realistic, highest-resolution 3D simulation of star formation to date. The result is a visually stunning, mathematically-driven marvel that allows viewers to float around a colorful gas cloud in 3D space while watching twinkling stars emerge.

Called STARFORGE (Star Formation in Gaseous Environments), the computational framework is the first to simulate an entire gas cloud -- 100 times more massive than previously possible and full of vibrant colors -- where stars are born.

It also is the first simulation to simultaneously model star formation, evolution and dynamics while accounting for stellar feedback, including jets, radiation, wind and nearby supernovae activity. While other simulations have incorporated individual types of stellar feedback, STARFORGE puts them altogether to simulate how these various processes interact to affect star formation.

Using this beautiful virtual laboratory, the researchers aim to explore longstanding questions, including why star formation is slow and inefficient, what determines a star's mass and why stars tend to form in clusters.

The researchers have already used STARFORGE to discover that protostellar jets -- high-speed streams of gas that accompany star formation -- play a vital role in determining a star's mass. By calculating a star's exact mass, researchers can then determine its brightness and internal mechanisms as well as make better predictions about its death.

Newly accepted by the Monthly Notices of the Royal Astronomical Society, an advanced copy of the manuscript, detailing the research behind the new model, appeared online today. An accompanying paper, describing how jets influence star formation, was published in the same journal in February 2021.

"People have been simulating star formation for a couple decades now, but STARFORGE is a quantum leap in technology," said Northwestern's Michael Grudi?, who co-led the work. "Other models have only been able to simulate a tiny patch of the cloud where stars form -- not the entire cloud in high resolution. Without seeing the big picture, we miss a lot of factors that might influence the star's outcome."

"How stars form is very much a central question in astrophysics," said Northwestern's Claude-André Faucher-Giguère, a senior author on the study. "It's been a very challenging question to explore because of the range of physical processes involved. This new simulation will help us directly address fundamental questions we could not definitively answer before."

Grudi? is a postdoctoral fellow at Northwestern's Center for Interdisciplinary Exploration and Research in Astrophysics (CIERA). Faucher-Giguère is an associate professor of physics and astronomy at Northwestern's Weinberg College of Arts and Sciences and member of CIERA. Grudi? co-led the work with Dávid Guszejnov, a postdoctoral fellow at the University of Texas at Austin.

From start to finish, star formation takes tens of millions of years. So even as astronomers observe the night sky to catch a glimpse of the process, they can only view a brief snapshot.

"When we observe stars forming in any given region, all we see are star formation sites frozen in time," Grudi? said. "Stars also form in clouds of dust, so they are mostly hidden."

For astrophysicists to view the full, dynamic process of star formation, they must rely on simulations. To develop STARFORGE, the team incorporated computational code for multiple phenomena in physics, including gas dynamics, magnetic fields, gravity, heating and cooling and stellar feedback processes. Sometimes taking a full three months to run one simulation, the model requires one of the largest supercomputers in the world, a facility supported by the National Science Foundation and operated by the Texas Advanced Computing Center.

The resulting simulation shows a mass of gas -- tens to millions of times the mass of the sun -- floating in the galaxy. As the gas cloud evolves, it forms structures that collapse and break into pieces, which eventually form individual stars. Once the stars form, they launch jets of gas outward from both poles, piercing through the surrounding cloud. The process ends when there is no gas left to form anymore stars.

Already, STARFORGE has helped the team discover a crucial new insight into star formation. When the researchers ran the simulation without accounting for jets, the stars ended up much too large -- 10 times the mass of the sun. After adding jets to the simulation, the stars' masses became much more realistic -- less than half the mass of the sun.

"Jets disrupt the inflow of gas toward the star," Grudi? said. "They essentially blow away gas that would have ended up in the star and increased its mass. People have suspected this might be happening, but, by simulating the entire system, we have a robust understanding of how it works."

Beyond understanding more about stars, Grudi? and Faucher-Giguère believe STARFORGE can help us learn more about the universe and even ourselves.

"Understanding galaxy formation hinges on assumptions about star formation," Grudi? said. "If we can understand star formation, then we can understand galaxy formation. And by understanding galaxy formation, we can understand more about what the universe is made of. Understanding where we come from and how we're situated in the universe ultimately hinges on understanding the origins of stars."

"Knowing the mass of a star tells us its brightness as well as what kinds of nuclear reactions are happening inside it," Faucher-Giguère said. "With that, we can learn more about the elements that are synthesized in stars, like carbon and oxygen -- elements that we are also made of."

The challenges that many women face in today's labour market are well documented, from lower employment rates than men to lower rates of pay. Previous studies have considered how the burden of family care, which often falls largely on women's shoulders, has contributed to this imbalance. However, few of these studies have considered why women are the ones to bear that care burden.
A new study, published in the KeAi journal China Economic Quarterly International, has used data from China to investigate the impact of the concept of gender roles on women's employment and earnings.

Study author, Chuanchuan Zhang, of China's Zhejiang University, explains: "Traditionally, studies on women's labour supply behaviour and labour market outcomes have mainly focused on economic, institutional and policy constraints. They have paid little attention to individual preferences or social beliefs.

"In recent years, with more and more interdisciplinary studies drawing on economics, psychology and sociology, researchers are looking at this topic from the perspectives of psychology, individual preferences and social concepts.

"For our study, we looked at the role of the community's concept of gender roles. And we found that the more traditional that perception, the less likely women are to be employed. For those who are employed, their total personal income and labour earnings are likely to be lower than men's."

Zhang, and his co-author Jingwen Wang, of China's Tsinghua University, began by collecting data on the numbers of March 8th Red Banner Pacesetters awarded locally in China in 1960 and 1979. These are honours that recognize outstanding women in China. They then used the awards as a proxy measure of the impact of women's liberation movements, and discovered that, over the course of those 19 years, the movements had significantly weakened traditional attitudes towards gender roles.

Wang explains: "This study shows that gender roles in Chinese culture, such as the traditional idea of "the husband is the breadwinner, the wife the housekeeper", are an important factor affecting Chinese women's labour market outcomes.

"However, although the traditional gender norm is deeply rooted, it is still significantly affected by economic and social changes such as women's liberation movements. To fundamentally correct employment and earnings inequality in China, it is necessary to gradually change traditional gender norms through cultural publicity and education, so we can create a cultural institutional environment that supports women's development."

The coronavirus pandemic has upended nearly every aspect of everyday life and continues to have devastating effects worldwide. It has also taken a significant toll on cardiovascular clinicians, many of whom provide direct care to patients with COVID-19, according to results of a new survey presented at the American College of Cardiology's 70th Annual Scientific Session.

Among those surveyed, burnout increased from 20% to 38% during the peak of the pandemic. Rates of burnout pre- and peak COVID-19 increased across all members of the cardiology team and was particularly striking among cardiovascular team members, which researchers said may be because they were more likely at the bedside as patients were dying. Among all cardiovascular clinicians--cardiologists, physician assistants, nurse practitioners, nurses, pharmacists and imaging technologists--half provided direct care to patients with COVID-19, and yet 1 out of 5 reported not having adequate personal protective equipment (PPE). Not surprisingly, the rate of burnout was higher in this group.

"We know from previous studies that burnout is pervasive in cardiology and medicine in general, but we felt it was important to take the temperature of our colleagues amid the COVID-19 pandemic. The prevalence of burnout among cardiovascular professionals nearly doubled when comparing pre- to peak COVID-19 levels," said Laxmi Mehta, MD, vice chair of wellness for the Department of Internal Medicine at the Ohio State University Wexner Medical Center and the study's lead author. "It clearly shows that there are lots of opportunities to improve the work environment; COVID-19 has really put a magnifying glass on the fact that things were bad and now have significantly worsened."

The survey revealed that some cardiovascular clinicians are thinking about leaving their jobs, in some cases, because of COVID-19. Plans to reduce clinical work hours in the next year, leave their current practice or retire early were reported by 23%, 13% and 13% of respondents, respectively, and notably higher among those who reported feeling burnt out. For some, COVID-19 is the key influencer for these decisions, with 17% of clinicians planning to reduce their clinical work hours, 12% planning to leave their current practice and 11% planning to retire due to COVID-19. The survey also revealed financial stressors exacerbated by COVID-19, with 41% of respondents reporting that their salary had been reduced to some degree. Roughly the same percentage of clinicians also reported inadequate health system support during the pandemic related to workers' basic needs, such as food, lodging, transportation, childcare and emotional support.

"Health systems need to take steps to help ensure basic safety, financial and personal needs of cardiology clinicians especially in the wake of COVID-19," Mehta said. "There are also still many unknowns with emerging variants and as our communities open more, some people are choosing not to get vaccinated, not to mention on top of the already taxed health systems, there are additional burdens of caring for patients with cardiovascular disease who delayed care and are now sicker than they would have been if they presented earlier."

The mini-Z survey on burnout was sent via email in November 2020 to 10,019 cardiologists, fellows-in-training and cardiovascular team members. A total of 1,288 people responded to the survey (456 U.S. and 436 international cardiologists, 128 trainees and 268 cardiovascular team members). Since peaks in COVID-19 disease activity differed by region, questions were structured to ask about feelings of burnout before COVID-19 and during the peak of COVID-19 in their region.

Burnout rates were lower among international cardiology professionals compared to U.S.-based peers. This data will be harder to interpret as each region has its own contributors to burnout that may differ, and there may be some inherent bias in who completed the survey, Mehta said.

Supporting clinician wellness by providing potential solutions to alleviate some of the job pressures associated with burnout has become a strategic priority for the American College of Cardiology, said Mehta, who serves as chair of the ACC's Task Force on Clinician Well-Being.

"Burnout is a metric, but well-being is the goal and what we are striving for," she said. "While we are resilient, these results show that we really need to be focusing on fixing the work environment, including ensuring that we have enough PPE, feeling valued and safe at work, improving team dynamics and efficiencies, which are all essential whether there is COVID-19 or not. Organizations need to focus on improving workforce care not just patient care."

The study is limited in that it relied on respondents' own interpretation of burnout. Mehta and her team will be examining the data more closely to understand gender and career stage differences.

Using more sensitive and frequent repeat testing of a blood test that indicates heart injury to guide the treatment of low-risk patients with symptoms of a possible heart attack resulted in patients being discharged earlier and receiving fewer cardiac stress tests but did not improve patient outcomes after one year, according to research presented at the American College of Cardiology's 70th Annual Scientific Session. In fact, a subset of patients receiving this more sensitive and frequent blood testing protocol were more likely to have a heart attack or to die during the one-year follow-up period compared with patients whose treatment was informed by the results of conventional blood testing procedures.

Troponins are proteins found in heart muscle that are released into the bloodstream when the heart muscle is damaged. Clinicians test for troponin in the blood when a patient visits a hospital emergency room with chest pain or other symptoms. While the detection of troponin in the blood may signal that a patient is having a heart attack, other heart problems, including heart failure or atrial fibrillation, or conditions such as a blood clot in the lungs or kidney disease can also cause elevated troponin levels.

"We wanted to know whether giving physicians greater information about troponin levels within a zero/one-hour repeat-testing protocol would change how they managed patients and whether such changes would lead to improvements in outcomes," said Derek Chew, MBBS, MPH, PhD, professor of cardiology at Flinders University in Adelaide, Australia, and principal investigator of the study. "We found that using high-sensitivity troponin in a rapid repeat-testing protocol, with recommendations for subsequent patient management, may have changed how physicians managed patients, but this did not lead to better outcomes."

Newer, highly sensitive laboratory assays are now routinely used to measure two types of troponin, known as troponin T and troponin I, in the blood. This randomized clinical trial used an assay that can detect levels of troponin T as low as five nanograms per liter (ng/L). By contrast, older, less-sensitive troponin tests accurately detected troponin levels only down to 29 ng/L. Few randomized controlled trials have looked at whether using the newer, more-sensitive troponin tests leads to better outcomes for patients, Chew said.

The study involved 3,378 patients (median age 59 years, 53% male) who visited emergency rooms at four metropolitan centers across South Australia with chest pain or other symptoms of a possible heart attack. Patients were eligible for the study if the results of their initial electrocardiogram, which measures electrical signals in the heart, did not show clear signs that they were experiencing inadequate blood supply to the heart muscle.

The participants were randomly assigned to one of two groups. Participants in the standard-care group received a troponin test on arrival at the emergency department and a second test three hours later. Treating physicians were blinded to the test results below 29 ng/L (i.e., the less-sensitive troponin assay level), in accordance with standards of practice at the time, and subsequent care was at the treating physician's discretion.

In the intervention group, participants also received a troponin test on arrival at the emergency department, but they received a second test sooner--just one hour after the first. The results provided to physicians were unblinded, allowing them to see the troponin result down to a level of 5 ng/L (i.e., the high-sensitivity troponin assay level). Based on the initial high-sensitivity troponin test result and the change in the troponin level over one hour, participants were categorized as "rule out," "rule in" or "further observation" for a heart attack, with guidance for subsequent care provided based on their category. The study's primary endpoint was time to a heart attack or death from any cause during the 12-month follow-up period.

Follow-up data were available for 3,270 participants (108 withdrew from the study by 12 months). For 92% of participants, both initial troponin T tests showed levels below 29 ng/L. Patients in the intervention group were discharged earlier than those in the standard-care group and underwent fewer stress tests (which evaluate how well the heart performs during exercise) and slightly more angiograms (which use X-rays to assess blood flow through the arteries in the heart).

Overall, the researchers found no statistically significant differences in the number of heart attacks or deaths between the two groups during the 12-month follow-up period. However, in the subset of patients whose initial troponin levels were below 29 ng/L, 3.7% of those in the intervention group had a heart attack or died within the follow-up period, compared with 2.3% in the standard-care group. This difference amounted to a 60% increase in the risk of a heart attack or death for this subset of patients.

"This finding may imply that the practice changes observed with the use of a zero/one-hour, high-sensitivity troponin T testing protocol--fewer stress tests and slightly more angiograms--may be associated with an increase in the risk of death or a heart attack within 12 months," Chew said. "However, it is possible that this finding occurred by chance, and therefore it should be interpreted with caution. Overall, the finding may signal the continued utility of functional testing, such as stress tests, and a need for reconsideration of downstream investigations and therapies in the large presenting population with low-level troponin elevations."

People with extremely high levels of triglycerides (a type of fat in the blood) and a specific genetic profile saw a substantial reduction in triglycerides after taking the human monoclonal antibody evinacumab compared with those taking a placebo, in a study presented at the American College of Cardiology's 70th Annual Scientific Session.

Severe hypertriglyceridemia is a rare disorder that causes extremely high levels of triglycerides, an accumulation of fat in the blood that can lead to heart, liver and pancreatic disease. People with severe hypertriglyceridemia commonly have triglyceride levels of 1,000 mg/dL (less than 150 mg/dL is considered normal and above 200 mg/dL is considered high) that cannot be adequately controlled with dietary restrictions or available medications.

"This trial has important clinical implications for this population with severe hypertriglyceridemia," said Robert S. Rosenson, MD, professor of medicine in cardiology and director of metabolism and lipids for the Mount Sinai Health System and the study's lead author. "It also demonstrates the importance of genetic testing in people with severe hypertriglyceridemia because by performing genetic testing you are able to tell which individuals will respond to this therapy and which are unlikely to respond."

Evinacumab is a monoclonal antibody currently approved for treating familial hypercholesterolemia (FH), a condition that causes extremely high cholesterol. Previous clinical trials found that evinacumab reduced triglycerides, as well as LDL or "bad" cholesterol, in people with FH. Evinacumab works by binding to angiopoietin-like protein 3 (ANGPTL3), a protein regulating cholesterol and triglycerides.

To study evinacumab's effects on triglycerides, the new phase 2 trial enrolled 51 patients with hypertriglyceridemia at 17 sites in four countries in North America and Europe. The patients did not have FH and had a history of triglyceride levels of 1,000 mg/dL and prior hospitalization for acute pancreatitis. At the time of screening, patients' triglyceride levels were 500 mg/dL or higher despite maintaining a strict diet. Acute pancreatitis is a common complication of hypertriglyceridemia.

Two-thirds of the trial participants were randomly assigned to receive evinacumab via intravenous infusion at a dosage of 15 mg/kg every four weeks for a total of 24 weeks. One-third received a placebo for the first 12 weeks (the double-blind portion of the study) and then received evinacumab for the second 12 weeks. All participants underwent genetic testing to assess mutations in LPL pathway genes, which provide instructions for making an enzyme called lipoprotein lipase that plays a critical role in breaking down tryglicerides.

At the end of the 12-week placebo-controlled double-blind period, the median triglyceride level dropped by more than 800 mg/dL (57%) in patients taking evinacumab, compared with an overall increase of 50 mg/dL (1.8%) in participants taking a placebo. The magnitude of triglyceride lowering with evinacumab was highly dependent on participants' genetic profile. Those with a double copy of certain mutations in LPL pathway genes had essentially no benefit from evinacumab, whereas patients with a single mutation or no mutations in LPL pathway genes saw triglyceride reductions of around 80%. Among patients with no identifiable LPL mutations, changes in the double-blind treatment and single-blind treatment (primary endpoint) showed a mean reduction in triglycerides of 27.1% and a median reduction of 68.8%.

While other therapies will be needed for patients with the double copy of certain LPL mutations, researchers said these new findings suggest evinacumab may be a promising therapeutic option for those with the appropriate genetic profile.

"Severe hypertriglyceridemia is a severe, unrelenting condition that impairs quality of life," Rosenson said. "Many patients have their first episode of pancreatitis in their teenage years and often end up in intensive care. Most lipid-lowering therapies don't work in these individuals, and that's why we need alternative therapies for them."

Adverse events such as abdominal pain, acute pancreatitis and headache occurred in about 70% of patients in both groups, but there was no significant difference in the rate of adverse events between those taking evinacumab and those taking a placebo. While the trial was not designed to determine an effect on the occurrence of acute pancreatitis, the majority of acute pancreatitis events occurred either when patients were receiving placebo or more than four weeks after completing evinacumab treatment. A separate study is now underway to determine whether evinacumab reduces recurrent pancreatitis by lowering triglycerides.

Rosenson said future studies could investigate evinacumab's potential benefits for patients with elevations in both triglycerides and LDL cholesterol, a combination often seen in patients with diabetes. "By lowering triglycerides by 60-80% and LDL cholesterol by 50% on top of statins and other medications, this agent has an opportunity to impact cardiovascular disease in these very high-risk individuals," Rosenson said.

As a phase 2 trial, the study was limited by its small sample size. Further studies with a broader patient population and larger sample size could further elucidate evinacumab's potential benefits for lowering triglycerides.