How evolution tamed a deadly virus and why we should still worry

The story of the rise and fall of western equine encephalitis as a lethal disease offers essential lessons about how a pathogen can gain or lose its ability to jump from animals to humans.

That story is captured in newly published research from Harvard Medical School that identifies the mechanisms the western equine encephalitis virus used to infect humans and matches changes in that ability over time to a decline in illness and deaths caused by the pathogen.

The study results, published July 24 in Nature, offer important lessons for public health experts looking to prepare for future outbreaks, the researchers said.

The work took many unexpected turns, the researchers said. The findings challenge some of the basic assumptions that scientists have relied on in their attempts to understand how viruses interact with human cells and what causes outbreaks to ebb and flow, such as the notion that any given virus targets one host receptor to gain entry and infect cells.

"This was a real scientific detective story," said study senior author Jonathan Abraham, associate professor of microbiology in the Blavatnik Institute at Harvard Medical School. "The virus kept surprising us and taught us some important lessons about how to study viruses."

The researchers identified the specific proteins expressed on host cells that different strains of the virus have used to infect a variety of animals, including horses, humans, and birds over the last century. Their findings tied differences in the virus's ability to sicken humans and horses to changes in the viral genome that left the virus unable to target proteins found in humans and horses, while leaving intact the virus's ability to infect birds and reptiles that serve as reservoirs for the virus.

The surprising diversity and variability in the virus's ability to infect host cells highlights the importance of studying viruses broadly across time, space, and host species to track potential outbreaks and monitor for emerging and re-emerging viruses.

A virus changes

The protagonist in the story is the western equine encephalitis virus (WEEV), a member of a viral family known as alphaviruses.

One key to understanding how a virus interacts with a host is identifying the precise path it takes to enter cells and cause infection.

WEEV and others in the alphavirus family typically attach a spike protein to a compatible protein -- the receptor -- on the surface of a host cell. Once attached to the host receptor, the virus enters the cell. Once inside the cell, the virus hijacks the cells' armamentarium to enable its own replication, spread, and survival.

The researchers made harmless replicas of various viral strains collected from different times and places and tested their ability to infect host cells in lab dishes. They also tested some of the strains in mice.

Several deadly strains of WEEV are known to cause severe brain inflammation in both horses and humans. Some years, thousands of horses were killed and hundreds of humans were sickened. Case fatality rates for people were as high as 15 percent in North America in the early and middle decades of the 20th century.

Abraham's group found that some of these early strains could stick their spike proteins to several different types of receptors to enter animal cells. That was an unexpected finding because the prevailing dogma in virology thus far has been that viruses typically attack by targeting only one type of host cell receptor.

The team observed that the strains circulating during the years of frequent outbreaks could use multiple receptors that are expressed on brain cells of humans and horses, including proteins known as PCDH10 and VLDLR.

Although the virus still circulates between birds, mosquitoes, and other animals, the most recent outbreak in the United States in humans was in 1987, according to the Centers for Disease Control and Prevention. Since then, there have been only five cases identified in the United States.

By contrast, when the researchers tested more recently isolated strains recovered from mosquitos in California in 2005, they found that the viral spike protein failed to recognize the human receptors, but could still interact with similar proteins found in birds.

Based on these findings, the researchers hypothesize that the virus had evolved, perhaps because horses can be vaccinated and are no longer prevalent enough in the agriculture or transportation industries to serve as effective amplifiers for the virus. Alternatively, the researchers note, the virus may have evolved through simple antigenic drifting, a process by which random mutations cause a series of small changes to a viral genome that, over time, may end up changing the way a virus interacts with its host. Whatever the reason, the researchers said, subtle shifts in the shape of the viral spike proteins changed the cellular receptors with which the virus could connect.

This change in targetable host receptors is likely the central reason why the virus "submerged" as a human pathogen in North America, the research team said. This newly gleaned appreciation of the dynamic complexity of viral receptors is an essential tool for understanding how this virus or others like it might one day re-emerge, the scientists said.

"We need to understand what happens to viruses when they submerge, to better prepare for when they re-emerge," said first author Wanyu Li, a Harvard Kenneth C. Griffin Graduate School of Arts and Sciences doctoral student in the virology program in the Harvard Division of Medical Sciences at HMS.

For example, knowing whether dangerous versions of the pathogen persist in isolated populations of insects, or if the virus has gained the ability to infect other animals, could provide important early warning signs for potential resurgences of illnesses that are thought to have disappeared.

A virus's complex behavior

Through their experiments, the researchers discovered that certain old WEEV strains behaved differently than expected.

The team used eastern equine encephalitis virus -- a deadlier cousin of WEEV -- as a control in some experiments. In one test, the team found that an old strain of WEEV could use the same receptor as the eastern virus, which is something that newer WEEV strains could not do. They also found different strains of WEEV that used different receptors. Some strains could stick to avian versions of the receptor protein but not those expressed in human or equine cells.

The findings serve as an important reminder that viruses are part of a dynamic system and that the viruses themselves are dynamic, with subtle but significant differences across time and geography -- a notion that was powerfully underscored by the rapidly shapeshifting SARS-CoV-2 virus that fueled the COVID-19 pandemic, the researchers said.

"It was a wake-up call," Abraham said. "It's telling us that we can't just study one strain of a virus and assume we know the whole story. Viruses seem simple, but they're quite complex, and they're constantly changing."

Applying lessons to pandemic preparedness

In standard virology, researchers often only check a limited number of viral strains. These new findings show that that's not enough to truly understand the virus.

"There's so much more biology to be learned by exploring the diversity of these complex systems," Abraham said. He also noted that it's necessary to explore as much of that viral diversity as possible in order to prepare for possible outbreaks.

Many viruses circulate in insects and animals that live around us, Abraham said. Some, like the tick-borne infection Powassan, which is endemic in New England, occasionally flare up to cause deadly or debilitating disease.

There could be many reasons for the flare-ups, Abraham said. Are there different strains of Powassan that carry different levels of risk? Is it an environmental change or an evolutionary shift in the pathogen itself that causes new outbreaks? Looking at all these aspects and the breadth of viral diversity will help researchers predict and protect against outbreaks.

In another twist, as Abraham and his team conducted their experiments, a new outbreak of WEEV occurred in South America, which had also seen steep declines in the disease in recent years. The viral populations in South and North America appear to be genetically distinct, and the South American strain of the virus doesn't remain viable long enough for migrating birds to transfer it from one continent to the other regularly. Still, Abraham noted, the new outbreak in South America emphasizes the importance of vigilance and of improving scientific understanding of these volatile, shapeshifting viruses.

"WEEV's return caught everyone by surprise," Li said. "Now with its cellular host receptors known, we have the tools to understand the molecular aspects of WEEV's re-emergence."

Abraham and collaborators are now investigating the strains associated with recent outbreak in South America.

"One small shift in the viral genome, in the intensity of a rainy season that allows mosquitos to proliferate, or in the place humans live or work, could trigger an outbreak," Abraham said. "The more we know, the better we'll be able to protect ourselves."

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Short-term exposure to high levels of air pollution kills 1 million globally every year

Every year, more than one million deaths globally occur because of exposure to short-term (hours to days) fine particulate matter (PM2.5) in air pollution, according to a new report, with Eastern Asia reporting more than 50% of deaths attributable to short-term PM2.5 globally.

To date most studies have focused on the health impacts of living in cities where pollution levels are consistently high, ignoring the frequent "spikes" in pollution that can impact smaller urban areas that occur for instance landscape fires, dust, and other intermittent extreme air-pollution concentration events.

The Monash University study, looking at mortality and pollution levels of PM2.5 in over 13,000 cities and towns across the globe in the two decades to 2019, is published today in The Lancet Planetary Health.

Led by Professor Yuming Guo, the study is important because it is the first to look at short-term exposure globally -- rather than the long-term impacts of persistent exposure such as for people living in cities with high pollution levels.

The researchers found that breathing in PM2.5 for even a few hours, and up to a few days, results in more than one million premature deaths occurring worldwide every year, particularly in Asia and Africa, and more than a fifth (22.74%) of them occurred in urban areas.

According to Professor Guo, the short-term health effects of being exposed to air pollution have been well documented, "such as the megafires in Australia during the so-called Black Summer of 2019-20 which were estimated to have led to 429 smoke-related premature deaths and 3230 hospital admissions as a result of acute and persistent exposure to extremely high levels of bushfire-related air pollution," he said.

"But this is the first study to map the global impacts of these short bursts of air pollution exposure."

The authors add that because of the high population densities in urban areas together with high levels of air pollution, "understanding the mortality burden associated with short-term exposure toPM2.5 in such areas is crucial for mitigating the negative effects of air pollution on the urban population."

According to the study:

• Asia accounted for approximately 65.2% of global mortality due to short-term PM2.5 exposure
• Africa 17.0%
• Europe 12.1%
• The Americas 5.6%
• Oceania 0.1%

The mortality burden was highest in crowded, highly polluted areas in eastern Asia, southern Asia, and western Africa with the fraction of deaths attributable to short-term PM2.5 exposure in eastern Asia was more than 50% higher than the global average.

Most areas in Australia saw a small decrease in the number of attributable deaths, but the attributable death fraction increased from 0.54% in 2000 to 0.76% in 2019, which was larger than any other subregions.

One potential reason could be the increasing frequency and scale of extreme weather-related air pollution events, such as bushfire events in 2019.

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Daily step count of 9,000 to 10,000 may counteract risk of death and cardiovascular disease in highly sedentary people

In good news for office workers, a new study from the University of Sydney's Charles Perkins Centre (Australia) has found increasing your step count may counteract the health consequences of too much sedentary time each day.

The study of over 72,000 people, published in the British Journal of Sports Medicine, found every additional step up to around 10,000 steps a day was linked to reduced risk of death (39 percent) and cardiovascular disease (21 percent) regardless of how much remaining time was spent sedentary.

Previous studies have shown an association between greater daily step count and lower levels of death and CVD, and separate studies have linked high levels of sedentary behaviour with increased risks of CVD and death. However, this is the first to objectively measure, via wrist-worn wearables, if daily steps could offset the health risks of high sedentary behaviour.

Lead author and research fellow, Dr Matthew Ahmadi said: "This is by no means a get out of jail card for people who are sedentary for excessive periods of time, however, it does hold an important public health message that all movement matters and that people can and should try to offset the health consequences of unavoidable sedentary time by upping their daily step count."

Senior author Professor Emmanuel Stamatakis, Director of the Mackenzie Wearables Research Hub at the Charles Perkins Centre, said this growing body of physical activity research using device-based measurement provided huge opportunities for public health.

"Step count is a tangible and easily understood measure of physical activity that can help people in the community, and indeed health professionals, accurately monitor physical activity. We hope this evidence will inform the first generation of device-based physical activity and sedentary behaviour guidelines, which should include key recommendations on daily stepping," said Professor Stamatakis.

How the study was conducted

Researchers used data on 72,174 individuals (average age 61; 58% female) from the UK Biobank study -- a major biomedical database -- who had worn an accelerometer device on their wrist for seven days to measure their physical activity. The accelerometer data were used to estimate daily step count and time spent sedentary, that is sitting or lying down while awake.

The research team then followed the health trajectory of the participants by linking hospitalisation data and death records.

The median daily step count for participants was 6222 steps/day, and 2200 steps/day (the lowest 5 percent of daily steps among all participants) was taken as the comparator for assessing the impact on death and CVD events of increasing step count.

The median time spent sedentary was 10.6 hours/day, so study participants sedentary for 10.5 hours/day or more were considered to have high sedentary time while those who spent less than 10.5 hours/day sedentary were classified as low sedentary time.

Adjustments were made to eliminate biases, such as excluding participants with poor health, who were underweight or had a health event within two years of follow-up. Researchers also took into account factors such as age, sex, ethnicity, education, smoking status, alcohol consumption, diet and parental history of CVD and cancer.

Findings

Over an average 6.9 years follow up, 1633 deaths and 6190 CVD events occurred.

After taking account of other potential influences, the authors calculated that the optimal number of steps per day to counteract high sedentary time was between 9000 to 10000 steps/day, which lowered mortality risk by 39 percent and incident CVD risk by 21 percent.

In both cases, 50 percent of the benefit was achieved at between 4000 and 4500 steps a day.

Study limitations

This is an observational study so can't establish direct cause and effect. And although the large sample size and long follow-up allowed the risk of bias to be reduced, the authors acknowledge the possibility that other unmeasured factors could affect results. As steps and sedentary time were obtained in a single time point, this could also lead to bias, they add.

Read more at Science Daily

High temperatures may have caused over 70,000 excess deaths in Europe in 2022

The burden of heat-related mortality during the summer of 2022 in Europe may have exceeded 70,000 deaths according to a study led by the Barcelona Institute for Global Health (ISGlobal), a research centre supported by the "la Caixa" Foundation. The authors of the study, published in The Lancet Regional Health -- Europe, revised upwards initial estimates of the mortality associated with record temperatures in 2022 on the European continent.

In an earlier study, published in Nature Medicine, the same team used epidemiological models applied to weekly temperature and mortality data in 823 regions in 35 European countries and estimated the number of heat-related premature deaths in 2022 to be 62,862.

In that study, the authors acknowledged that the use of weekly data would be expected to underestimate heat-related mortality, and pointed out that daily time-series data are required to accurately estimate the impact of high temperatures on mortality.

The objective of the new study was to develop a theoretical framework capable of quantifying the errors arising from the use of aggregated data, such as weekly and monthly temperature and mortality time-series.

Models based on temporally aggregated data are useful because aggregated data are available in real-time from institutions such as Eurostat, facilitating quantification of the health hazard within a few days of its emergence.

To develop a theoretical framework, the research team aggregated daily temperatures and mortality records from 147 regions in 16 European countries.

They then analysed and compared the estimates of heat- and cold-related mortality by different levels of aggregation: daily, weekly, 2-weekly and monthly.

Analysis revealed differences in epidemiological estimates according to the time scale of aggregation.

In particular, it was found that weekly, 2-weekly and monthly models underestimated the effects of heat and cold as compared to the daily model, and that the degree of underestimation increased with the length of the aggregation period.

Specifically, for the period 1998-2004, the daily model estimated an annual cold and heat-related mortality of 290,104 and 39,434 premature deaths, respectively, while the weekly model underestimatedthese numbers by 8.56% and 21.56%, respectively.

"It is important to note that the differences were very small during periods of extreme cold and heat, such as the summer of 2003, when the underestimation by the weekly data model was only 4.62%," explains Joan Ballester Claramunt, the ISGlobalresearcherwho leads the European Research Council's EARLY-ADAPT project.

The team used this theoretical framework to revise the mortality burden attributed to the record temperatures experienced in 2022 in their earlier study.

According to the calculations made using the new methodological approach, that study underestimated the heat-related mortality by 10.28%, which would mean that the actual heat-related mortality burden in 2022, estimated using the daily data model, was 70,066 deaths, and not 62,862 deaths as originally estimated.

Using weekly data to analyse the effects of temperatures in the short term

"In general, we do not find models based on monthly aggregated data useful for estimating the short-term effects of ambient temperatures," explains Ballester.

"However, models based on weekly data do offer sufficient precision in mortality estimates to be useful in real-time practice in epidemiological surveillance and to inform public policies such as, for example, the activation of emergency plans for reducing the impact of heat waves and cold spells."

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Evidence from the remains of 1918 flu pandemic victims contradicts long-held belief that healthy young adults were particularly vulnerable

New analysis of the remains of victims of the 1918 influenza pandemic, which killed an estimated 50 million people worldwide, contradicts the widespread belief the flu disproportionately impacted healthy young adults.

Because so many people fell ill so quickly, physicians at the time believed the healthy were as likely to die from the flu as those who had already been sick or frail. Despite numerous historical accounts, though, it turns out there is no concrete scientific evidence to support that belief.

Researchers at McMaster University and the University of Colorado Boulder who analyzed victims' age of death and studied lesions on victims' bones report that the most susceptible to dying of the flu had exhibited signs of previous environmental, social and nutritional stress.

"Our circumstances -- social, cultural and immunological -- are all intertwined and have always shaped the life and death of people, even in the distant past," explains Amanda Wissler, an assistant professor in the Department of Anthropology at McMaster and lead author on the study, published today in the journal PNAS.

"We saw this during COVID-19, where our social backgrounds and our cultural backgrounds influenced who was more likely to die, and who was likely to survive," she says.

Much of the research on the 1918 pandemic relies on historical documentation such as vital statistics, census data and life insurance records, none of which include information on pre-existing conditions, or general environmental, dietary or other chronic stressors which can impact one's overall health over the course of a lifetime.

For the study, researchers examined the skeletal remains of 369 individuals from the Hamman-Todd Documented skeletal collection, which is housed at the Cleveland Museum of Natural History. All had died between 1910 and 1938. The sample was divided into two groups: a control group who had died before the pandemic, and those who died during the pandemic.

A living person's skeletal structure may undergo lasting changes due to poor health, resulting in diminished height, irregular growth, developmental tooth defects and other indicators.

The team searched for lesions, or indicators of stress, on the shinbones of the pandemic victims. New bone formation occurs in response to inflammation caused by physical trauma or infection, for example. Researchers can determine if a lesion had been active, in the midst of healing or had completely healed, all of which provide evidence of underlying conditions.

"By comparing who had lesions, and whether these lesions were active or healing at the time of death, we get a picture of what we call frailty, or who is more likely to die. Our study shows that people with these active lesions are the most frail," says Sharon DeWitte, a biological anthropologist at the University Colorado Boulder and co-author on the study.

Preexisting medical conditions such as asthma or congestive heart failure are common risk factors which can contribute to poor outcomes from infectious diseases such as influenza.

Racism and institutional discrimination can amplify these effects, as evidenced in the COVID-19 pandemic, say researchers. During the Black Death in London, for example, individuals who had previously suffered environmental, nutritional and disease stressors were more likely to die from the plague than their healthier peers.

"The results of our work counter the narrative and the anecdotal accounts of the time," says Wissler. "This paints a very complicated picture of life and death during the 1918 pandemic."

Read more at Science Daily

Being fit partially offsets negative impact of high blood pressure

High fitness levels may reduce the risk of death from cardiovascular disease in men with high blood pressure, according to a 29-year study published today in the European Journal of Preventive Cardiology, a journal of the ESC.

"This was the first study to evaluate the joint effects of fitness and blood pressure on the risk of dying from cardiovascular disease," said study author Professor Jari Laukkanen of the University of Eastern Finland, Kuopio, Finland. "The results suggest that being fit helps protect against some of the negative effects of high blood pressure."

Nearly 1.3 billion adults aged 30 to 79 years worldwide have high blood pressure (hypertension). Hypertension is a major risk factor for heart attack and stroke and a leading cause of premature death globally. Previous studies have shown that high cardiorespiratory fitness is linked with greater longevity. This study examined the interplay between blood pressure, fitness and risk of death from cardiovascular disease.

The study included 2,280 men aged 42 to 61 years living in eastern Finland and enrolled in the Kuopio Ischaemic Heart Disease Risk Factor Study. Baseline measurements were conducted between 1984 and 1989. These included blood pressure and cardiorespiratory fitness, which was assessed as maximal oxygen uptake while riding a stationary bicycle. Blood pressure was classified as normal or high, and fitness was classified as low, medium or high.

The average age at baseline was 53 years. Participants were followed up until 2018. During a median follow up of 29 years, there were 644 deaths due to cardiovascular disease. The risk of death from cardiovascular disease was analysed after adjusting for age, body mass index, cholesterol levels, smoking status, type 2 diabetes, coronary heart disease, use of antihypertensive medication, alcohol consumption, physical activity, socioeconomic status, and high sensitivity C-reactive protein (a marker of inflammation).

Considering blood pressure alone, compared to normal values, high blood pressure was associated with a 39% increased risk of cardiovascular mortality (hazard ratio [HR] 1.39; 95% confidence interval [CI] 1.17-1.63). Considering fitness alone, compared with high levels, low fitness was associated with a 74% elevated likelihood of cardiovascular death (HR 1.74; 95% CI 1.35-2.23).

To evaluate the joint associations of blood pressure and fitness with risk of cardiovascular death, participants were categorised into four groups: 1) normal blood pressure and high fitness (this was the reference group for comparison); 2) normal blood pressure and low fitness; 3) high blood pressure and high fitness; 4) high blood pressure and low fitness.

Men with high blood pressure and low fitness had a more than doubled risk of cardiovascular death compared to those with normal blood pressure and high fitness (HR 2.35; 95% CI 1.81-3.04). When men with high blood pressure had high fitness levels, their elevated risk of cardiovascular risk persisted but was weaker: it was 55% higher than those with normal blood pressure and high fitness (HR 1.55; 95% CI 1.16-2.07).

Professor Laukkanen said: "Both high blood pressure and low fitness levels were each associated with an increased risk of cardiovascular death. High fitness levels attenuated, but did not eliminate, the increased risk of cardiovascular mortality in men with elevated blood pressure."

The paper states: The inability of cardiorespiratory fitness to completely eliminate the risk of cardiovascular mortality in those with high blood pressure could partly be due to the strong, independent and causal relationship between blood pressure and cardiovascular disease.

Professor Laukkanen concluded: "Getting blood pressure under control should remain a goal in those with elevated levels. Our study indicates that men with high blood pressure should also aim to improve their fitness levels with regular physical activity. In addition to habitual exercise, avoiding excess body weight may enhance fitness."

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Ludwig van Beethoven's genome sheds light on chronic health problems and cause of death

In 1802, Ludwig van Beethoven asked his brothers to request that his doctor, J.A. Schmidt, describe his malady -- his progressive hearing loss -- to the world upon his death so that "as far as possible at least the world will be reconciled to me after my death." Now, more than two centuries later, a team of researchers reporting in the journal Current Biology on March 22 have partially fulfilled his wish by analyzing DNA they lifted and pieced together from locks of his hair.

"Our primary goal was to shed light on Beethoven's health problems, which famously include progressive hearing loss, beginning in his mid- to late-20s and eventually leading to him being functionally deaf by 1818," said Johannes Krause from the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

"We were unable to find a definitive cause for Beethoven's deafness or gastrointestinal problems," Krause says. "However, we did discover a number of significant genetic risk factors for liver disease. We also found evidence of an infection with hepatitis B virus in at latest the months before the composer's final illness. Those likely contributed to his death."

As commonly happens when people analyze DNA, the researchers uncovered another surprise. Beethoven's Y chromosome doesn't match that of any of five modern-day relatives carrying the same last name and sharing, on the basis of genealogical records, a common ancestor with Beethoven's paternal line. The finding points to an extramarital "event" somewhere over the generations on Beethoven's father's side.

"This finding suggests an extrapair paternity event in his paternal line between the conception of Hendrik van Beethoven in Kampenhout, Belgium in c.1572 and the conception of Ludwig van Beethoven seven generations later in 1770, in Bonn, Germany," says Tristan Begg, now at the University of Cambridge, U.K.

The idea for the work was conceived by Begg and study co-author William Meredith almost a decade ago. They were motivated by Beethoven's request for postmortem studies to describe his illness and make it public. In the new study, the team, also including Toomas Kivisild of Katholieke Universiteit Leuven in Belgium, relied on recent improvements in ancient DNA analysis; these improvements have enabled whole-genome sequencing from small quantities of historical hair.

First, they analyzed independently sourced locks of hair attributed to Beethoven, only five of which they confirmed came from the same European male. They deemed these five to be "almost certainly authentic" and used them to sequence Beethoven's genome to 24-fold genomic coverage.

Medical biographers had earlier suggested that Beethoven had many substantially heritable health conditions. But the researchers in this study couldn't find in his genome an explanation for Beethoven's hearing disorder or gastrointestinal problems. They did find that he was genetically predisposed to liver disease.

Further study of other DNA in his samples suggested that he also had a hepatitis B infection at least during the months leading up to his death. "Together with the genetic predisposition and his broadly accepted alcohol consumption, these present plausible explanations for Beethoven's severe liver disease, which culminated in his death," they write.

The researchers note that previous analyses suggesting that Beethoven had lead poisoning turned out to have been based on a sample that wasn't Beethoven's at all; instead, it came from a female. Future studies testing for lead, opiates, and mercury must be based on authenticated samples, they say.

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Bird flu associated with hundreds of seal deaths in New England in 2022

Researchers at Cummings School of Veterinary Medicine at Tufts University found that an outbreak of highly pathogenic avian influenza (HPAI) was associated with the deaths of more than 330 New England harbor and gray seals along the North Atlantic coast in June and July 2022, and the outbreak was connected to a wave of avian influenza in birds in the region.

The study was published on March 15 in the journal Emerging Infectious Disease.

HPAI is more commonly known as bird flu, and the H5N1 strain has been responsible for about 60 million poultry deaths in the U.S. since October 2020, with similar numbers in Europe. The virus was known to have spilled over from birds into mammals, such as mink, foxes, skunk, and bears, but those were mostly small, localized events. This study is among the first to directly connect HPAI to a larger scale mortality event in wild mammals.

The co-first authors on the paper -- virologist and senior scientist Wendy Puryear and post-doctoral researcher Kaitlin Sawatzki, who both work in the Runstadler Lab at Cummings School -- have been researching viruses in seals for years. They credit their findings in the new study to a unique and robust data set made possible by a collaboration with wildlife clinics and rehabilitation and response organizations in the region, in particular with Tufts Wildlife Clinic and director Maureen Murray, V03, associate clinical professor at Cummings School, and an author on the paper.

"We have a better resolution and greater depth of detail on this virus than before because we were able to sequence it and detect changes almost in real time," said Puryear. "And we have pairings of samples, sometimes literally from a bird and a seal on the same beach."

The clinic has been conducting avian influenza surveillance on birds and some mammals since January 2022, shortly after this strain of avian influenza took a trans-Atlantic journey from Europe into the U.S. Through this testing, the team found a wide range of flu viruses, including at least three strains that crossed the Atlantic, and they witnessed consistent waves of infection in birds.

At the same time, in collaboration with NOAA's Greater Atlantic Region Marine Mammal Stranding Network, they were able to screen nearly all seals that came through the network, whether or not the animal appeared sick. The stranding network is composed of experts from state and federal wildlife and fisheries agencies, non-profit rehabilitation and response facilities, aquariums, and academic institutions who respond to strandings.

"Because of the genetic data that we gathered, we were the first to see a strain of the virus that's unique to New England. The data set will allow us to more meaningfully address questions of which animals are passing the virus to which animals and how the virus is changing," said Sawatzki.

How HPAI Is Transmitted

In addition to poultry, H5N1 also has had a huge impact on wild birds, especially sea birds. Multiple locations around the globe have experienced large die-offs, such as recently in Peru, where the virus killed 60,000 pelicans, penguins, and gulls.

At the time of the seal mortality event in New England, the virus was hitting gulls particularly hard, the researchers found. There are lots of ways gulls and other birds may transmit the virus to seals, they said. Seals and sea birds are coastal animals living in the same areas that have environmental contact, if not direct contact, since they share the same water and shoreline. A seal may contract the virus if it comes in contact with a sick bird's excrement or water contaminated by that excrement, or if it preys upon an infected bird.

The accepted knowledge is that H5N1 is nearly 100% fatal for domestic and wild birds other than waterfowl, and the same is proving true when it comes to spillover in wild mammals. All the seals that tested positive for HPAI were deceased at the time of sampling or succumbed shortly after. None of the animals that tested positive recovered. However, it's possible some asymptomatic or recovered cases never came into the stranding networks.

In addition to the seal mortality event in New England, which was the first time H5N1 was detected in marine mammals in the wild, other locations have lost marine mammals to the virus. Peru announced about 3,500 sea lions died from the virus, Canada reported a seal mortality event along the St. Lawrence Estuary, and there was a similar event with seals in the Caspian Sea, according to news reports from Russia.

A hotly debated topic among scientists is whether there has been mammal-to-mammal transmission of HPAI between seals.

"It's not surprising that you might have transmission between the seals, because it has happened with low pathogenic avian influenza," said Puryear. "However, we can't say definitively whether or not there has been mammal-to-mammal transmission of HPAI."

"To get strong evidence of mammal-to-mammal transmission, you need two things: lots of infected animals and time," explained Sawatzki. "Time for the virus to mutate, and time for the mutated virus to be transmitted to another seal. As the virus acquires mutations, we can see shared mutations in the sequences that are specific only to mammals and that haven't been seen in a bird before. We had the numbers, but this outbreak didn't last long enough to provide evidence for seal-to-seal transmission."

The research team found evidence that the virus mutated in a small number of seals. But fortunately, they have not seen a case of bird flu in seals along the Atlantic coast since the end of last summer. However, stranding season is about to start for harbor seals and gray seals, so they are bracing themselves for what might happen.

Prevention and Risk to Humans

The risk to the public remains low, according to the Centers for Disease Control and Prevention. Since December 2021, less than 10 human cases of H5N1 have been reported globally, and those cases occurred in people with direct exposure to infected poultry. There are no documented cases of human transmission for this variant.

However, there is the possibility it could become a larger issue for human health. Avian influenza emerged in 1996, and since 2003, 868 cases of human infection with H5N1 have been reported worldwide, according to the World Health Organization. Of those, 457 were fatal, roughly a 50% fatality rate.

"And that's why people get nervous about it," Puryear said.

There is a single-dose vaccine available for poultry, but it's not currently administered on a large scale -- in part because of cost and logistics, and in part because there's some concern it may make future surveillance of the virus more difficult. There's not much that can be done in terms of responding to the virus for wildlife, particularly given the scale at which infection is occurring.

Biosecurity is important in limiting the ways in which the virus can spread between and within species, the researchers said. For example, wild birds should be kept separate from domestic birds, such as backyard chickens. In addition, thorough and timely surveillance of domestic animals and wildlife is key to understanding how the virus is evolving to prepare the best possible vaccines and treatments.

Read more at Science Daily

Over 4% of summer mortality in European cities is attributable to urban heat islands

Over four percent of deaths in cities during the summer months are due to urban heat islands, and one third of these deaths could be prevented by reaching a tree cover of 30%, according to a modelling study published in The Lancet and led by the Barcelona Institute for Global Health (ISGlobal), an institution supported by "la Caixa" Foundation. The study results, obtained with data from 93 European cities, highlight the substantial benefits of planting more trees in cities to attenuate the impact of climate change.

Exposure to heat has been associated with premature mortality, cardiorespiratory disease and hospital admissions. This is particularly true for heat waves, but also occurs with moderately high temperatures in summer. Cities are especially vulnerable to higher temperatures. Less vegetation, higher population density, and impermeable surfaces for buildings and roads, including asphalt, lead to a temperature difference between the city and surrounding areas -- a phenomenon called urban heat island. Given the ongoing global warming and urban growth, this effect is expected to worsen over the next decades.

"Predictions based on current emissions reveal that heat-related illness and death will become a bigger burden to our health services over the next decades," says ISGlobal researcher Tamara Iungman, first author of the study.

An international team led by Mark Nieuwenhuijsen, director of the Urban Planning, Environment and Health Initiative at ISGlobal, estimated mortality rates of residents aged over 20 in 93 European cities (a total of 57 million inhabitants), between June and August 2015, and collected data on daily rural and urban temperatures for each city. The analyses were performed at a high-resolution level (areas of 250m x 250m). First, they estimated the premature mortality by simulating a hypothetical scenario without urban heat island. Second, they estimated the temperature reduction that would be obtained by increasing tree cover to 30% and the associated mortality that could be avoided.

"Our goal is to inform local decision-makers about the benefits of integrating green areas into all neighborhoods in order to promote more sustainable, resilient and healthy urban environments," explains Nieuwenhuijsen.

The protective effect of trees

The results show that, from June to August 2015, cities were on average 1.5oC warmer than the surrounding countryside. In total, 6,700 premature deaths could be attributed to hotter urban temperatures, which represents 4.3% of total mortality during the summer months and 1.8% of year-round mortality. One third of these deaths (2,644) could have been prevented by increasing tree cover up to 30%, thereby reducing temperatures. Overall, cities with the highest excess heat-mortality rates were in Southern and Eastern Europe, with these cities benefiting the most from an increase in tree cover.

The study highlights the substantial benefits of planting more trees in cities, although the authors acknowledge that this can be challenging in some cities due to their design, and that tree planting should be combined with other interventions such as green roofs or other temperature-reducing alternatives.

"Our results also show the need to preserve and maintain the trees that we already have because they are a valuable resource and it takes a long time to grow new trees. It is not only about increasing trees in the city, it is also about how they are distributed," says Nieuwenhuijsen.

The analyses were done for 2015 because population data were not available for later years, but, as Iungman points out, the study provides valuable information for adapting our cities and making them more resilient to the health impact of climate change. "Here we only looked at the cooling effect of trees, but making cities greener has many other health benefits, including longer life expectancy, fewer mental health problems and better cognitive functioning," she adds.

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Neuronal molecule makes prostate cancer more aggressive

Prostate cancer is the second most common cancer and the second leading cause of cancer death among American men. Now, researchers have discovered key molecular players that drive prostate cancer to progress into a highly aggressive form of the disease called neuroendocrine prostate cancer that currently has no effective treatment. The finding uncovers new avenues to explore for therapeutics to treat neuroendocrine prostate cancer.

"We have found novel pathways that promote neuroendocrine prostate cancer," says senior author Lucia R. Languino, PhD, a professor in the department of Pharmacology, Physiology and Cancer Biology and director of the Genetics, Genomics, and Cancer Biology PhD Program at Thomas Jefferson University. She and her team published the new research online on November 7, 2022 in the journal Scientific Reports.

Most prostate cancers are a type of disease called prostate adenocarcinoma. Other types of prostate cancer, including neuroendocrine tumors, are rare. However, unlike prostate adenocarcinoma, neuroendocrine prostate cancer is very aggressive and can quickly spread to other parts of the body. Treatments that are effective for adenocarcinomas in the prostate do not work against neuroendocrine prostate cancers.

Adenocarcinoma prostate cancers can progress into neuroendocrine prostate cancer. Until now, how this transition occurs has been a mystery.

To better understand how neuroendocrine prostate cancer develops, Dr. Languino and colleagues looked for biomarkers of the disease. In previous work, they discovered that a molecule known as aVb3 integrin is abundant in mice and humans with neuroendocrine prostate cancer, but missing in prostate adenocarcinoma.

To look for molecules unique to neuroendocrine prostate cancer, the researchers found that aVb3 integrin expression in prostate cancer cells bumped up the expression of a known marker of neuroendocrine prostate cancer and significantly increased the expression of a molecule called Nogo receptor 2 (NgR2).

The finding "was a big discovery," Dr. Languino says, who is also a researcher with the Sidney Kimmel Cancer Center -- Jefferson Health. That's because NgR2 is a protein found in nerve cells, where it contributes to neuronal functions. It has never before been studied in cancer, of any kind.

Dr. Languino and her colleagues wanted to find out what this molecule, a neuronal protein, is doing in cancer.

An initial experiment revealed that NgR2 binds the aVb3 integrin. The scientists also saw that in mice with neuroendocrine prostate tumors, aVb3 integrin and NgR2 were both present in the primary tumor and in cancerous lesions that had formed in the lungs of the animals. A follow-up experiment made it clear that both aVb3 integrin and NgR2 are necessary for neuroendocrine prostate cancers.

When Dr. Languino and her team lowered the amount of NgR2 in neuroendocrine prostate cancer cells, neuroendocrine markers also decreased. The results suggest that NgR2 plays a role in the development of neuroendocrine prostate cancer. Lowering the amount of NgR2 also reduced the ability of cancer cells to grow and move, indicating that NgR2 may have a hand in cancer spreading to other parts of the body, in a process known as metastasis. Metastases are often what makes cancers fatal.

"These two molecules, aVb3 integrin and NgR2, seem to create a combination that is lethal," Dr. Languino says.

She and her colleagues are now looking for a molecule or antibody that would block the effect of NgR2, or the aVb3 integrin/NgR2 complex, to inhibit their ability to promote neuroendocrine prostate cancer growth and development, and make the cancer more susceptible to therapy.

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Pace as important as 10,000 steps for health

10,000 steps a day is the 'sweet spot' for lowered risk of disease and death, but how fast you walk could be just as important according to new research.

The studies, published in the journals JAMA Internal Medicine and JAMA Neurology, monitored 78, 500 adults with wearable trackers -- making these the largest studies to objectively track step count in relation to health outcomes.

The researchers from the University of Sydney, Australia and University of Southern Denmark found lowered risk of dementia, heart disease, cancer and death are associated with achieving 10,000 steps a day. However, a faster stepping pace like a power walk showed benefits above and beyond the number of steps achieved.

"The take-home message here is that for protective health benefits people could not only ideally aim for 10,000 steps a day but also aim to walk faster," said co-lead author Dr Matthew Ahmadi, Research Fellow at the University of Sydney's Charles Perkins Centre and Faculty of Medicine and Health.

'For less active individuals, our study also demonstrates that as low as 3,800 steps a day can cut the risk of dementia by 25 percent," said co-lead author Associate Professor Borja del Pozo Cruz from the University of Southern Denmark and senior researcher in health at the University of Cadiz.

Key points:
 

• Every 2,000 steps lowered risk of premature death incrementally by 8 to 11 percent, up to approximately 10,000 steps a day.
• Similar associations were seen for cardiovascular disease and cancer incidence.
• A higher number of steps per day was associated with a lower risk of all-cause dementia
• 9,800 steps was the optimal dose linked to lower risk of dementia by 50 percent, however risk was reduced by 25 percent at as low as 3,800 steps a day
• Stepping intensity or a faster pace showed beneficial associations for all outcomes (dementia, heart disease, cancer and death) over and above total daily steps.

"Step count is easily understood and widely used by the public to track activity levels thanks to the growing popularity of fitness trackers and apps, but rarely do people think about the pace of their steps," said senior author Emmanuel Stamatakis, Professor of Physical Activity, Lifestyle and Population Health at the University of Sydney.

"Findings from these studies could inform the first formal step-based physical activity guidelines and help develop effective public health programs aimed at preventing chronic disease."

How was the study conducted?

The study drew on data from UK Biobank to link up step count data from 78,500 UK adults aged 40 to 79 years with health outcomes 7 years on. Participants wore a wrist accelerometer to measure physical activity over a period of 7 days (minimum 3 days, including a weekend day and monitoring during sleep periods).

With ethics consent, this information was linked with participants' health records through several data sources and registries including inpatient hospital, primary care records, and cancer and death registries.

Only those who were free of cardiovascular disease, cancer or dementia at baseline and disease-free in the first two years of the study were included in the final assessment. Statistical adjustments were also made for confounders, such as the fact that people who do more steps generally walk faster.

The researchers note that the studies are observational, meaning they cannot show direct cause and effect, however, note the strong and consistent associations seen across both studies at the population level.

"The size and scope of these studies using wrist-worn trackers makes it the most robust evidence to date suggesting that 10,000 steps a day is the sweet spot for health benefits and walking faster is associated with additional benefits," said Dr Matthew Ahmadi.

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New study finds lowest risk of death was among adults who exercised 150-600 minutes/week

An analysis of more than 100,000 participants over a 30-year follow-up period found that adults who perform two to four times the currently recommended amount of moderate or vigorous physical activity per week have a significantly reduced risk of mortality, according to new research published today in the American Heart Association's flagship, peer-reviewed journal Circulation. The reduction was 21-23% for people who engaged in two to four times the recommended amount of vigorous physical activity, and 26-31% for people who engaged in two to four times the recommended amount of moderate physical activity each week.

It is well documented that regular physical activity is associated with reduced risk of cardiovascular disease and premature death. In 2018, the United States Department of Health and Human Services' Physical Activity Guidelines for Americans recommended that adults engage in at least 150-300 minutes/week of moderate physical activity or 75-150 minutes/week of vigorous physical activity, or an equivalent combination of both intensities. The American Heart Association's current recommendations, which are based on HHS's Physical Activity Guidelines, are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week or vigorous aerobic exercise, or a combination of both.

"The potential impact of physical activity on health is great, yet it remains unclear whether engaging in high levels of prolonged, vigorous or moderate intensity physical activity above the recommended levels provides any additional benefits or harmful effects on cardiovascular health," said Dong Hoon Lee, Sc.D., M.S., a research associate in the department of nutrition at the Harvard T.H. Chan School of Public Health in Boston. "Our study leveraged repeated measures of self-reported physical activity over decades to examine the association between long-term physical activity during middle and late adulthood and mortality."

Researchers analyzed mortality data and medical records for more than 100,000 adults gathered from two large prospective studies: the all-female Nurses' Health Study and the all-male Health Professionals Follow-up Study from 1988-2018. Participants whose data were examined were 63% female, and more than 96% were white adults. They had an average age of 66 years and an average body mass index (BMI) of 26 kg/m2 over the 30-year follow-up period.

Participants self-reported their leisure-time physical activity by completing a validated questionnaire for either the Nurses' Health Study or Health Professionals Follow-Up Study every two years. The publicly available questionnaires, which were updated and expanded every two years, included questions about health information, physician-diagnosed illnesses, family medical histories and personal habits such as cigarette and alcohol consumption and frequency of exercise. Exercise data was reported as the average time spent per week on various physical activities over the past year. Moderate activity was defined as walking, lower-intensity exercise, weightlifting and calisthenics. Vigorous activity included jogging, running, swimming, bicycling and other aerobic exercises.

The analysis found that adults who performed double the currently recommended range of either moderate or vigorous physical activity each week had the lowest long-term risk of mortality.

The analysis also found:

• Participants who met the guidelines for vigorous physical activity had an observed 31% lower risk of CVD mortality and 15% lower risk of non-CVD mortality, for an overall 19% lower risk of death from all causes.
• Participants who met the guidelines for moderate physical activity had an observed 22-25% lower risk of CVD mortality and 19-20% lower risk of non-CVD mortality, for an overall 20-21% lower risk of death from all causes.
• Participants who performed two to four times above the recommended amount of long-term vigorous physical activity (150-300 min/week) had an observed 27-33% lower risk of CVD mortality and 19% non-CVD mortality, for an overall 21-23% lower risk of death from all causes.
• Participants who performed two to four times above the recommended amount of moderate physical activity (300-600 min/week) had an observed 28-38% lower risk of CVD mortality and 25-27% non-CVD mortality, for an overall 26-31% lower risk of mortality from all causes.

In addition, no harmful cardiovascular health effects were found among the adults who reported engaging in more than four times the recommended minimum activity levels. Previous studies have found evidence that long-term, high-intensity, endurance exercise, such as marathons, triathlons and long-distance bicycle races, may increase the risk of adverse cardiovascular events, including myocardial fibrosis, coronary artery calcification, atrial fibrillation and sudden cardiac death.

"This finding may reduce the concerns around the potential harmful effect of engaging in high levels of physical activity observed in several previous studies," Lee noted.

However, engaging in long-term, high intensity physical activity (?300 minutes/week) or moderate intensity physical activity (?600 minutes/week) at levels more than four times the recommended weekly minimum did not provide any additional reduction in risk of death.

"Our study provides evidence to guide individuals to choose the right amount and intensity of physical activity over their lifetime to maintain their overall health," Lee said. "Our findings support the current national physical activity guidelines and further suggest that the maximum benefits may be achieved by performing medium to high levels of either moderate or vigorous activity or a combination."

He also noted that people who perform less than 75 minutes of vigorous activity or less than 150 minutes of moderate activity per week may have greater benefits on mortality reduction by consistently performing approximately 75-150 minutes of vigorous activity or 150-300 minutes of moderate exercise per week, or an equivalent combination of both, over the long term.

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Air pollution caused 2,780 deaths, illnesses, and IQ loss in children in Massachusetts in 2019

Air pollution remains a silent killer in Massachusetts, responsible for an estimated 2,780 deaths a year and for measurable cognitive loss in Bay State children exposed to fine particulate pollutants in the air they breathe, according to a new study by researchers at Boston College's Global Observatory on Planetary Health.

The study was supported by the Barr Foundation and is the first to examine far-reaching public health consequences of air pollution in the state on a town-by-town basis. The study found air-pollution-related disease, death and IQ loss occur in every city and town regardless of demographics or income level. Highest rates were in the most economically disadvantaged and socially underserved cities and towns.

The Boston College team estimates the cumulative impact on childhood cognitive development in Massachusetts in 2019 was a loss of almost 2 million Performance IQ points, or more than 2 IQ points for the average child, according to the report, published today in the journal Environmental Health. IQ loss impairs children's school performance and reduces graduation rates, the team noted.

"We are talking about the impacts of air pollution at a very local level in Massachusetts -- not just statewide," said lead author Boston College Professor of Biology Philip J. Landrigan, MD, director of the Observatory. "This report gives the people in every city and town the opportunity to see for themselves the quality of the air they and their families are breathing and the dangerous health implications for both adults and children as a consequence of air pollution."

"All of these health effects occurred at pollution levels below current EPA standards," Landrigan noted.

The average level of fine particulate pollution across Massachusetts in 2019 was 6.3 micrograms per cubic meter, and levels ranged from a low of 2.77 micrograms per cubic meter in Worcester County to a high of 8.26 in Suffolk County. The U.S. Environmental Protection Agency standard is 12 micrograms per cubic meter, and the World Health Organization's recommended guideline is 5.

"Clearly, current EPA air pollution standards are not adequately protecting public health," Landrigan said.

Town-by-town air pollution information is not typically available, given there are not enough air quality monitoring stations in the state. The team determined levels for all cities and towns using available data and computer modeling.

While Massachusetts meets federal clean air guidelines and air pollution in the U.S. has declined 70 percent since the passage of the Clean Air Act in the 1970s -- when Landrigan and other scientists successfully pushed for the removal of lead from gasoline -- unclean air at current levels still poses health hazards to both healthy individuals and those with other ailments or illnesses.

"We do not have the level of air pollution you see in China or India and because it is mostly invisible today people tend to forget about air pollution and we get complacent," Landrigan said. "We hope to break through this complacency and increase awareness. Air pollution is killing 2,780 people in Massachusetts each year, nearly 5 percent of all deaths in the state, and that is a big deal. Air pollution is something we can fix. We know the steps that need to be taken to reduce fatalities and the impact on our children and grandchildren. Now citizens in every city and town across the Commonwealth need to urge our elected officials to take those necessary steps."

Additional findings include:
 

• Of the 2,780 deaths attributable to air pollution in Massachusetts in 2019, at least 2,185 were due to lung cancer 1,677 to heart disease, 343 to chronic lung disease, and 200 to stroke.
• Air pollution was responsible for 15,386 cases of pediatric asthma and an estimated 308 low-birthweight babies (5.5 lbs. or less).

More than 95 percent of air pollution in Massachusetts results from the combustion of fossil fuels. Cars, trucks, buses, planes, trains and ships produced two-thirds of pollutant emissions-655,000 tons -- in 2017, the most recent year for which data were available. Power plants, industrial facilities, and home heating and cooking produced 283,000 tons. In all, these sources emitted 938,000 tons of pollutants.

Fossil fuel combustion is also the major source of the carbon dioxide and other greenhouse gases that drive global climate change, which the researchers said should further incentivize Massachusetts to reduce air pollution and greenhouse gas emissions by transitioning to cleaner fuels.

"Air pollution harms our environment and young people, and these burdens disproportionately impact environmental justice communities," said Kathryn Wright, the Barr Foundation's Senior Program Officer for Clean Energy. "Meaningful action on climate change requires us to swiftly address air pollution from transportation and our energy system and its many harmful effects."

Fine particulate air pollution is linked to multiple non-communicable diseases in adults, including cardiovascular disease, stroke, lung cancer and diabetes. Among infants and children air pollution increases risk for premature birth, low birthweight, stillbirth, impaired lung development, and asthma.

"All of these adverse health effects occur at fine particulate matter pollution levels below the U.S. Environmental Protection Agency's current annual standard of 12 micrograms per cubic meter," said Landrigan. "So even for a state like Massachusetts, which registered below that standard, air pollution is a formidable public health threat that needs urgently to be addressed."

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Adding salt to your food at the table is linked to higher risk of premature death

People who add extra salt to their food at the table are at higher risk of dying prematurely from any cause, according to a study of more than 500,000 people, published in the European Heart Journal today (Monday).

Compared to those who never or rarely added salt, those who always added salt to their food had a 28% increased risk of dying prematurely. In the general population about three in every hundred people aged between 40 and 69 die prematurely. The increased risk from always adding salt to food seen in the current study suggests that one more person in every hundred may die prematurely in this age group.

In addition, the study found a lower life expectancy among people who always added salt compared to those who never, or rarely added salt. At the age of 50, 1.5 years and 2.28 years were knocked off the life expectancy of women and men, respectively, who always added salt to their food compared to those who never, or rarely, did.

The researchers, led by Professor Lu Qi, of Tulane University School of Public Health and Tropical Medicine, New Orleans, USA, say their findings have several public health implications.

"To my knowledge, our study is the first to assess the relation between adding salt to foods and premature death," he said. "It provides novel evidence to support recommendations to modify eating behaviours for improving health. Even a modest reduction in sodium intake, by adding less or no salt to food at the table, is likely to result in substantial health benefits, especially when it is achieved in the general population."

Assessing overall sodium intake is notoriously difficult as many foods, particularly pre-prepared and processed foods, have high levels of salt added before they even reach the table. Studies assessing salt intake by means of urine tests often only take one urine test and so do not necessarily reflect usual behaviour. In addition, foods that are high in salt are often accompanied by foods rich in potassium, such as fruit and vegetables, which is good for us. Potassium is known to protect against the risk of heart diseases and metabolic diseases such as diabetes, whereas sodium increases the risk of conditions such as cancer, high blood pressure and stroke.

For these reasons, the researchers chose to look at whether or not people added salt to their foods at the table, independent of any salt added during cooking.

"Adding salt to foods at the table is a common eating behaviour that is directly related to an individual's long-term preference for salty-tasting foods and habitual salt intake," said Prof. Qi. "In the Western diet, adding salt at the table accounts for 6-20% of total salt intake and provides a unique way to evaluate the association between habitual sodium intake and the risk of death."

The researchers analysed data from 501,379 people taking part in the UK Biobank study. When joining the study between 2006 and 2010, the participants were asked, via a touch-screen questionnaire, whether they added salt to their foods (i) never/rarely, (ii) sometimes, (iii) usually, (iv) always, or (v) prefer not to answer. Those who preferred not to answer were not included in the analysis. The researchers adjusted their analyses to take account of factors that could affect outcomes, such as age, sex, race, deprivation, body mass index (BMI), smoking, alcohol intake, physical activity, diet and medical conditions such as diabetes, cancer and heart and blood vessel diseases. They followed the participants for a median (average) of nine years. Premature death was defined as death before the age of 75 years.

As well as finding that always adding salt to foods was linked to a higher risk of premature death from all causes and a reduction in life expectancy, the researchers found that these risks tended to be reduced slightly in people who consumed the highest amounts of fruit and vegetables, although these results were not statistically significant.

"We were not surprised by this finding as fruits and vegetables are major sources of potassium, which has protective effects and is associated with a lower risk of premature death," said Prof. Qi.

He added: "Because our study is the first to report a relation between adding salt to foods and mortality, further studies are needed to validate the findings before making recommendations."

In an editorial to accompany the paper, Professor Annika Rosengren, a senior researcher and professor of medicine at the Sahlgrenska Academy, University of Gothenburg, Sweden, who was not involved with the research, writes that the net effect of a drastic reduction in salt intake for individuals remains controversial.

"Given the various indications that a very low intake of sodium may not be beneficial, or even harmful, it is important to distinguish between recommendations on an individual basis and actions on a population level," she writes.

She concludes: "Classic epidemiology argues that a greater net benefit is achieved by the population-wide approach (achieving a small effect in many people) than from targeting high-risk individuals (a large effect but only achieved in a small number of people). The obvious and evidence-based strategy with respect to preventing cardiovascular disease in individuals is early detection and treatment of hypertension, including lifestyle modifications, while salt-reduction strategies at the societal level will lower population mean blood pressure levels, resulting in fewer people developing hypertension, needing treatment, and becoming sick. Not adding extra salt to food is unlikely to be harmful and could contribute to strategies to lower population blood pressure levels."

A strength of Prof. Qi's study is the large number of people included. It also has some limitations, which include: the possibility that adding salt to food is an indication of an unhealthy lifestyle and lower socio-economic status, although analyses attempted to adjust for this; there was no information on the quantity of salt added; adding salt may be related to total energy intake and intertwined with intake of other foods; participation in UK Biobank is voluntary and therefore the results are not representative of the general population, so further studies are needed to confirm the findings in other populations.

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Increasing heat waves affect up to half a billion people

Climate change is a reality and extremely high temperatures have been reported by India and Pakistan in the spring. In a new scientific journal article, researchers from the University of Gothenburg, amongst others, paint a gloomy picture for the rest of the century. Heat waves are expected to increase, affecting up to half a billion people every year. In turn, they can lead to food shortages, deaths and refugee flows when the heat reaches levels that exceed what humans can tolerate. But this does not have to happen if measures are put in place to reach the Paris Agreement targets, the researchers say.

In India and Pakistan, heat waves with temperatures above 40 degrees in the shade are a directly life-threatening form of extreme weather. In a new article in the journal Earth's Future, researchers have outlined different scenarios for the consequences of heat waves in South Asia to the year 2100.

"We established a link between extreme heat and population. In the best scenario, we succeeded in meeting the targets in the Paris Agreement, which added roughly two heat waves per year, exposing about 200 million people to the heat waves. But if countries continue to contribute to the greenhouse effect as they are still doing now, clearing and building on land that is actually helping to lower global temperatures, we believe that there could be as many as five more heat waves per year, with more than half a billion people being exposed to them, by the end of the century," says Deliang Chen, Professor of Physical Meteorology at the University of Gothenburg and one of the authors of the article.

Population growth drives emissions

The study identifies the Indo-Gigantic Plains beside the Indus and Ganges rivers as particularly vulnerable. This is a region of high temperatures, and it is densely populated. Deliang Chen points out that the link between heat waves and population works in both directions. The size of the population affects the number of future heat waves. A larger population drives emissions up as consumption and transport increase. Urban planning is also important. If new towns and villages are built in places that are less subject to heat waves, the number of people affected can be reduced.

"We hope that the leaders in the region such as India and Pakistan read our report and think about it. In our calculation model, the range for the number of people who will be exposed to heat waves is large. The actual numbers will depend on the path that these countries choose to take in their urban planning. It is future greenhouse gas and particulate emissions that will determine how many people are actually exposed. We can more than halve the population exposed to intense heat waves if we reduce emissions so that we reach the targets in the Paris Agreement. Both mitigation and adaptation measures can make a huge difference," says Deliang Chen.

Risk of a refugee wave

Heat waves are already causing major problems in India and Pakistan. Farmers have been hit hard when drought and heat has caused their wheat crops to fail, and their crops have moved to higher altitudes to escape the extreme heat. But this move has resulted in large acreages of trees being cleared; trees that have contributed to lowering temperatures.

"With a larger population, land use increases, which in itself can drive up temperatures further. Each heat wave will result in increased mortality and decreased productivity, since few people can work in 45-degree heat. I fear that if nothing is done, it can ultimately lead to a huge wave of migrations."

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Watching the death of a rare giant star

A University of Arizona-led team of astronomers has created a detailed, three-dimensional image of a dying hypergiant star. The team, led by UArizona researchers Ambesh Singh and Lucy Ziurys, traced the distribution, directions and velocities of a variety of molecules surrounding a red hypergiant star known as VY Canis Majoris.

Their findings, which they presented on June 13 at the 240th Meeting of the American Astronomical Society in Pasadena, California, offer insights, at an unprecedented scale, into the processes that accompany the death of giant stars. The work was done with collaborators Robert Humphreys from the University of Minnesota and Anita Richards from the University of Manchester in the United Kingdom.

Extreme supergiant stars known as hypergiants are very rare, with only a few known to exist in the Milky Way. Examples include Betelgeuse, the second brightest star in the constellation Orion, and NML Cygni, also known as V1489 Cygni, in the constellation Cygnus. Unlike stars with lower masses -- which are more likely to puff up once they enter the red giant phase but generally retain a spherical shape -- hypergiants tend to experience substantial, sporadic mass loss events that form complex, highly irregular structures composed of arcs, clumps and knots.

Located about 3,009 light-years from Earth, VY Canis Majoris -- or VY CMa, for short -- is a pulsating variable star in the slightly southern constellation of Canis Major. Spanning anywhere from 10,000 to 15,000 astronomical units (with 1 AU being the average distance between Earth and the sun) VY CMa is possibly the most massive star in the Milky Way, according to Ziurys.

"Think of it as Betelgeuse on steroids," said Ziurys, a Regents Professor with joint appointments in UArizona Department of Chemistry and Biochemistry and Steward Observatory, both part of the College of Science. "It is much larger, much more massive and undergoes violent mass eruptions every 200 years or so."

The team chose to study VY CMa because it is one of the best examples of these types of stars.

"We are particularly interested in what hypergiant stars do at end of their lives," said Singh, a fourth-year doctoral student in Ziurys' lab. "People used to think these massive stars simply evolve into supernovae explosions, but we are no longer sure about that."

"If that were the case, we should see many more supernovae explosions across the sky," Ziurys added. "We now think they might quietly collapse into black holes, but we don't know which ones end their lives like that, or why that happens and how."

Previous imaging of VY CMa with NASA's Hubble Space Telescope and spectroscopy showed the presence of distinct arcs and other clumps and knots, many extending thousands of AU from the central star. To uncover more details of the processes by which hypergiant stars end their lives, the team set out to trace certain molecules around the hypergiant and map them to preexisting images of the dust, taken by the Hubble Space Telescope.

"Nobody has been able to make a complete image of this star," Ziurys said, explaining that her team set out to understand the mechanisms by which the star sheds mass, which appear to be different from those of smaller stars entering their red giant phase at the end of their lives.

"You don't see this nice, symmetrical mass loss, but rather convection cells that blow through the star's photosphere like giant bullets and eject mass in different directions," Ziurys said. "These are analogous to the coronal arcs seen in the sun, but a billion times larger."

The team used the Atacama Large Millimeter Array, or ALMA, in Chile to trace a variety of molecules in material ejected from the stellar surface. While some observations are still in progress, preliminary maps of sulfur oxide, sulfur dioxide, silicon oxide, phosphorus oxide and sodium chloride were obtained. From these data, the group constructed an image of the global molecular outflow structure of VY CMa on scales that encompassed all ejected material from the star.

"The molecules trace the arcs in the envelope, which tells us molecules and dust are well-mixed," Singh said. "The nice thing about emissions of molecules at radio wavelengths is that they provide us with velocity information, as opposed to the dust emission, which is static."

By moving ALMA's 48 radio dishes into different configurations, the researchers were able to obtain information about the directions and velocities of the molecules and map them across the different regions of the hypergiant's envelope in considerable detail, even correlating them to different mass ejection events over time.

Processing the data required some heavy lifting in terms of computing power, Singh said.

"So far, we have processed almost a terabyte from ALMA, and we still receive data that we have to go through to get the best resolution possible," he said. "Just calibrating and cleaning the data requires up to 20,000 iterations, which takes a day or two for each molecule."

Read more at Science Daily

Cutting air pollution emissions would save 50,000 US lives, $600 billion each year

Eliminating air pollution emissions from energy-related activities in the United States would prevent more than 50,000 premature deaths each year and provide more than $600 billion in benefits each year from avoided illness and death, according to a new study by University of Wisconsin-Madison researchers.

Published today in the journal GeoHealth, the study reports the health benefits of removing dangerous fine particulates released into the air by electricity generation, transportation, industrial activities and building functions like heating and cooking -- also major sources of carbon dioxide emissions that cause climate change, since they predominantly rely on burning fossil fuels like coal, oil, and natural gas.

"Our work provides a sense of the scale of the air quality health benefits that could accompany deep decarbonization of the U.S. energy system," says Nick Mailloux, lead author of the study and a graduate student at the Center for Sustainability and the Global Environment in UW-Madison's Nelson Institute for Environmental Studies. "Shifting to clean energy sources can provide enormous benefit for public health in the near term while mitigating climate change in the longer term."

Working with scientists specializing in air quality and public health, Mailloux used a model from the U.S. Environmental Protection Agency to determine the health benefits from a complete reduction in emissions of fine particulate matter and of sulfur dioxide and nitrogen oxides. These compounds can form particulate matter once released into the atmosphere.

These pollutants contribute to health problems such as heart disease, stroke, chronic obstructive pulmonary disease, lung cancer and lower respiratory infections that can dramatically shorten lifespans. Doing away with these pollutants would save about 53,200 lives each year in the US, providing about $608 billion in benefits from avoided healthcare costs and loss of life, according to the researchers' analysis.

The researchers also studied the health effects if regions of the country were to act independently to reduce emissions instead of as part of a concerted nationwide effort. The effects can differ widely in different parts of the US, in part because of regional variations in energy use and population.

The Southwest, a region comprising Arizona, California and Nevada, would retain 95 percent of the benefits if it moved alone to eliminate fine particle emissions.

"In the Mountain region, though, most of the benefit of emissions removal is felt somewhere else," Mailloux says. "Just 32 percent of the benefit remains in states in the Mountain region. This is partly because there are large population centers downwind of the Mountain region that would also benefit."

Every region of the country sees more benefit from nationwide action than from acting on their own to reduce emissions.

"The Great Plains, for example, gets more than twice as much benefit from nationwide efforts as it does from acting alone," says Mailloux. "The more that states and regions can coordinate their emissions reductions efforts, the greater the benefit they can provide to us all."

The researchers hope that by describing the near-term payoffs on top of the threats of more distant climate impacts, the new study motivates more action on climate change.

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Air pollution responsible for 180,000 excess deaths in tropical cities

The international team of scientists aimed to address data gaps in air quality for 46* future megacities in Africa, Asia and the Middle East using space-based observations from instruments onboard NASA and European Space Agency (ESA) satellites for 2005 to 2018.

Published today in Science Advances, the study reveals rapid degradation in air quality and increases in urban exposure to air pollutants hazardous to health. Across all the cities, the authors found significant annual increases in pollutants directly hazardous to health of up to 14% for nitrogen dioxide (NO2) and up to 8% for fine particles (PM2.5), as well as increases in precursors of PM2.5 of up to 12% for ammonia and up to 11% for reactive volatile organic compounds.

The researchers attributed this rapid degradation in air quality to emerging industries and residential sources like road traffic, waste burning, and widespread use of charcoal and fuelwood.

Lead author Dr Karn Vohra (UCL Geography), who completed the study as a PhD student at the University of Birmingham, said: "Open burning of biomass for land clearance and agricultural waste disposal has in the past overwhelmingly dominated air pollution in the tropics. Our analysis suggests we're entering a new era of air pollution in these cities, with some experiencing rates of degradation in a year that other cities experience in a decade."

The scientists also found 1.5- to 4- fold increases in urban population exposure to air pollution over the study period in 40 of the 46 cities for NO2 and 33 of the 46 cities for PM2.5., caused by a combination of population growth and rapid deterioration in air quality.

According to the study, the increase in the number of people dying prematurely from exposure to air pollution was highest in cities in South Asia, in particular Dhaka, Bangladesh (totalling 24,000 people), and the Indian cities of Mumbai, Bangalore, Kolkata, Hyderabad, Chennai, Surat, Pune and Ahmedabad (totalling 100,000 people).

The researchers say that while the number of deaths in tropical cities in Africa are currently lower due to recent improvements in healthcare across the continent resulting in a decline in overall premature mortality, the worst effects of air pollution on health will likely occur in the coming decades.

Study co-author Dr Eloise Marais (UCL Geography) said: "We continue to shift air pollution from one region to the next, rather than learning from errors of the past and ensuring rapid industrialisation and economic development don't harm public health. We hope our results will incentivise preventative action in the tropics."

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Mysterious death of carbon star plays out like six-ring circus

Scientists studying V Hydrae (V Hya) have witnessed the star's mysterious death throes in unprecedented detail. Using the Atacama Large Millimeter/submillimeter Array (ALMA) and data from the Hubble Space Telescope (HST), the team discovered six slowly-expanding rings and two hourglass-shaped structures caused by the high-speed ejection of matter out into space. The results of the study are published in The Astrophysical Journal.

V Hya is a carbon-rich asymptotic giant branch (AGB) star located approximately 1,300 light-years from Earth in the constellation Hydra. More than 90-percent of stars with a mass equal to or greater than the Sun evolve into AGB stars as the fuel required to power nuclear processes is stripped away. Among these millions of stars, V Hya has been of particular interest to scientists due to its so-far unique behaviors and features, including extreme-scale plasma eruptions that happen roughly every 8.5 years and the presence of a nearly invisible companion star that contributes to V Hya's explosive behavior.

"Our study dramatically confirms that the traditional model of how AGB stars die -- through the mass ejection of fuel via a slow, relatively steady, spherical wind over 100,000 years or more -- is at best, incomplete, or at worst, incorrect," said Raghvendra Sahai, an astronomer at NASA's Jet Propulsion Laboratory, and the principal researcher on the study. "It is very likely that a close stellar or substellar companion plays a significant role in their deaths, and understanding the physics of binary interactions is both important across astrophysics and one of its greatest challenges. In the case of V Hya, the combination of a nearby and a hypothetical distant companion star is responsible, at least to some degree, for the presence of its six rings, and the high-speed outflows that are causing the star's miraculous death."

Mark Morris, an astronomer at UCLA and a co-author on the research added, "V Hydra has been caught in the process of shedding its atmosphere -- ultimately most of its mass -- which is something that most late-stage red giant stars do. Much to our surprise, we have found that the matter, in this case, is being expelled as a series of outflowing rings. This is the first and only time that anybody has seen that the gas being ejected from an AGB star can be flowing out in the form of a series of expanding 'smoke rings.'"

The six rings have expanded outward from V Hya over the course of roughly 2,100 years, adding matter to and driving the growth of a high-density flared and warped disk-like structure around the star. The team has dubbed this structure the DUDE, or Disk Undergoing Dynamical Expansion.

"The end state of stellar evolution -- when stars undergo the transition from being red giants to ending up as white dwarf stellar remnants -- is a complex process that is not well understood," said Morris. "The discovery that this process can involve the ejections of rings of gas, simultaneous with the production of high-speed, intermittent jets of material, brings a new and fascinating wrinkle to our exploration of how stars die."

Sahai added, "V Hya is in the brief but critical transition phase that does not last very long, and it is difficult to find stars in this phase, or rather 'catch them in the act. We got lucky and were able to image all of the different mass-loss phenomena in V Hya to better understand how dying stars lose mass at the end of their lives."

In addition to a full set of expanding rings and a warped disk, V Hya's final act features two hourglass-shaped structures -- and an additional jet-like structure -- that are expanding at high speeds of more than half a million miles per hour (240 km/s). Large hourglass structures have been observed previously in planetary nebulae, including MyCn 18 -- also known as the Engraved Hourglass Nebula -- a young emission nebula located roughly 8,000 light-years from Earth in the southern constellation of Musca, and the more well-known Southern Crab Nebula, an emission nebula located roughly 7,000 light-years from Earth in the southern constellation Centaurus.

Sahai said, "We first observed the presence of very fast outflows in 1981. Then, in 2022, we found a jet-like flow consisting of compact plasma blobs ejected at high speeds from V Hya. And now, our discovery of wide-angle outflows in V Hya connects the dots, revealing how all these structures can be created during the evolutionary phase that this extra-luminous red giant star is now in."

Due to both the distance and the density of the dust surrounding the star, studying V Hya required a unique instrument with the power to clearly see matter that is both very far away and also difficult or impossible to detect with most optical telescopes. The team enlisted ALMA's Band 6 (1.23mm) and Band 7 (.85mm) receivers, which revealed the star's multiple rings and outflows in stark clarity.

"The processes taking place at the end stages of low mass stars, and during the AGB phase in particular, have long fascinated astronomers and have been challenging to understand," said Joe Pesce, an astronomer and NSF program officer for NRAO/ALMA. "The capabilities and resolution of ALMA are finally allowing us to witness these events with the extraordinary detail necessary to provide some answers and enhance our understanding of an event that happens to most of the stars in the Universe."

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Good news for coffee lovers: Daily coffee may benefit the heart

Drinking coffee -- particularly two to three cups a day -- is not only associated with a lower risk of heart disease and dangerous heart rhythms but also with living longer, according to studies being presented at the American College of Cardiology's 71st Annual Scientific Session. These trends held true for both people with and without cardiovascular disease. Researchers said the analyses -- the largest to look at coffee's potential role in heart disease and death -- provide reassurance that coffee isn't tied to new or worsening heart disease and may actually be heart protective.

"Because coffee can quicken heart rate, some people worry that drinking it could trigger or worsen certain heart issues. This is where general medical advice to stop drinking coffee may come from. But our data suggest that daily coffee intake shouldn't be discouraged, but rather included as a part of a healthy diet for people with and without heart disease," said Peter M. Kistler, MD, professor and head of arrhythmia research at the Alfred Hospital and Baker Heart Institute in Melbourne, Australia, and the study's senior author. "We found coffee drinking had either a neutral effect -- meaning that it did no harm -- or was associated with benefits to heart health."

Kistler and his team used data from the UK BioBank, a large-scale prospective database with health information from over half a million people who were followed for at least 10 years. Researchers looked at varying levels of coffee consumption ranging from up to a cup to more than six cups a day and the relationship with heart rhythm problems (arrhythmias); cardiovascular disease, including coronary artery disease, heart failure and stroke; and total and heart-related deaths among people both with and without cardiovascular disease. Patients were grouped by how much coffee they reported drinking each day: 0, <1, 1, 2-3, 4-5, >5 cups/day. Coffee drinking was assessed from questionnaires completed upon entry into the registry. Overall, they either found no effect or, in many cases, significant reductions in cardiovascular risk after controlling for exercise, alcohol, smoking, diabetes and high blood pressure that could also play a role in heart health and longevity.

For the first study, researchers examined data from 382,535 individuals without known heart disease to see whether coffee drinking played a role in the development of heart disease or stroke during the 10 years of follow up. Participants' average age was 57 years and half were women. In general, having two to three cups of coffee a day was associated with the greatest benefit, translating to a 10%-15% lower risk of developing coronary heart disease, heart failure, a heart rhythm problem, or dying for any reason. The risk of stroke or heart-related death was lowest among people who drank one cup of coffee a day. Researchers did observe a U-shaped relationship with coffee intake and new heart rhythm problems. The maximum benefit was seen among people drinking two to three cups of coffee a day with less benefit seen among those drinking more or less.

The second study included 34,279 individuals who had some form of cardiovascular disease at baseline. Coffee intake at two to three cups a day was associated with lower odds of dying compared with having no coffee. Importantly, consuming any amount of coffee was not associated with a higher risk of heart rhythm problems, including atrial fibrillation (AFib) or atrial flutter, which Kistler said is often what clinicians are concerned about. Of the 24,111 people included in the analysis who had an arrhythmia at baseline, drinking coffee was associated with a lower risk of death. For example, people with AFib who drank one cup of coffee a day were nearly 20% less likely to die than non-coffee drinkers.

"Clinicians generally have some apprehension about people with known cardiovascular disease or arrhythmias continuing to drink coffee, so they often err on the side of caution and advise them to stop drinking it altogether due to fears that it may trigger dangerous heart rhythms," Kistler said. "But our study shows that regular coffee intake is safe and could be part of a healthy diet for people with heart disease."

Although two to three cups of coffee a day seemed to be the most favorable overall, Kistler said that people shouldn't increase their coffee intake, particularly if it makes them feel anxious or uncomfortable.

"There is a whole range of mechanisms through which coffee may reduce mortality and have these favorable effects on cardiovascular disease," he said. "Coffee drinkers should feel reassured that they can continue to enjoy coffee even if they have heart disease. Coffee is the most common cognitive enhancer -- it wakes you up, makes you mentally sharper and it's a very important component of many people's daily lives."

So how might coffee beans benefit the heart? People often equate coffee with caffeine, but coffee beans actually have over 100 biologically active compounds. These substances can help reduce oxidative stress and inflammation, improve insulin sensitivity, boost metabolism, inhibit the gut's absorption of fat and block receptors known to be involved with abnormal heart rhythms, Kistler said.

In a third study, researchers looked at whether there were any differences in the relationship between coffee and cardiovascular disease depending on whether someone drank instant or ground coffee or caffeinated or decaf. They found, once again, two to three cups a day to be associated with the lowest risk of arrhythmias, blockages in the heart's arteries, stroke or heart failure regardless of whether they had ground or instant coffee. Lower rates of death were seen across all coffee types. Decaf coffee did not have favorable effects against incident arrhythmia but did reduce cardiovascular disease, with the exception of heart failure. Kistler said the findings suggest caffeinated coffee is preferable across the board, and there are no cardiovascular benefits to choosing decaf over caffeinated coffees.

There are several important limitations to these studies. Researchers were unable to control for dietary factors that may play a role in cardiovascular disease, nor were they able to adjust for any creamers, milk or sugar consumed. Participants were predominantly white, so additional studies are needed to determine whether these findings extend to other populations. Finally, coffee intake was based on self-report via a questionnaire fielded at study entry. This should be considered when interpreting the study findings, though Kistler noted that research suggests people's dietary habits don't change much in adulthood or over time. Kistler said the results should be validated in randomized trials.

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