Culture

Emory MVA COVID-19 vaccine safe and effective in animal models

ATLANTA - Researchers at Yerkes National Primate Research Center, Emory University, have developed a COVID-19 vaccine that has proven safe and effective in mice and monkeys. Results from this National Institute of Allergy and Infectious Diseases (NIAID)-funded study are published online today in Immunity.

The Emory MVA COVID-19 vaccine approaches inducing protective immunity via modified vaccinia Ankara (MVA), a harmless version of a poxvirus that is well-known for its use in HIV/AIDS vaccines. Like the Moderna and Pfizer COVID-19 vaccines, the Emory MVA COVID-19 vaccine induces strong neutralizing antibodies, which support the immune system's ability to fight infections. The Emory MVA COVID-19 takes protection several steps further, starting with inducing killer CD8 T cells in addition to the neutralizing antibodies, providing a multi-pronged approach to halting SAR-COV-2. In addition, the Emory researchers say the vaccine is easily adaptable to address disease variants, can be used in combination with existing vaccines to improve their ability to combat variants and has the potential to be equally effective with a single dose.

Lead researcher Rama Amara, PhD, built the Emory MVA COVID-19 vaccine based on his more than 20 years of experience working with MVA and animal models to develop an HIV/AIDS vaccine. He and his Yerkes-based research team tested two MVA SARS-CoV-2 vaccines in mice. One of them, MVA/S, used the complete spike protein of coronavirus to induce strong neutralizing antibodies against SARS-CoV-2. In addition, this vaccine also induced a strong killer CD8 T cell response.

According to Amara, a researcher in Yerkes' Division of Microbiology and Immunology and the Emory Vaccine Center (EVC) as well as a Charles Howard Candler professor of microbiology and immunology at Emory School of Medicine (SOM), "Generating neutralizing antibodies is an important component of a successful COVID-19 vaccine because the antibodies can block the virus from entering the body's cells. It's as important to activate CD8 T cells that can clear infected cells, so this allows us to approach halting the virus two ways simultaneously. The CD8 T cells also provide ongoing value because they are key to working against other variants of the virus, especially if antibodies fail."

Based on the encouraging study results in mice, the Amara team advanced the MVA/S COVID-19 vaccine into a study with 10 rhesus monkeys at Yerkes. For five animals, the researchers gave two doses of the vaccine a month apart and then challenged them with SARS-CoV-2. The researchers also challenged a group of five monkeys that received a placebo MVA vaccine, which did not contain any genes from the COVID-19 virus. The virus grew to high levels in the lungs of all five placebo animals by the second day, but was below detection limits in all five MVA/S-vaccinated animals. "Comparing the virus in vaccine and placebo groups provided clear results the MVA/S vaccine is safe and effective against SARS-CoV-2," says Amara. "These results are even more promising because the MVA/S-vaccinated animals did not show any signs of inflammation in the lungs such as what medical professional are seeing in humans who have COVID-19."

Rafi Ahmed, PhD, director of the EVC and an international expert in how vaccines work, credits Amara for his comprehensive approach. "Based on decades of research, we know MVA vaccines are safe, effective and can be used in combination with other vaccines, including mRNA vaccines, to enhance the immune system's response. The Emory MVA COVID-19 vaccine, which builds on the MVA HIV vaccine Dr. Amara co developed that recently completed phase 2a human clinical trials, scores multiple goals by producing neutralizing antibodies, inducing killer CD8 T cells and preventing lung inflammation. This multi-layered approach to developing a COVID-19 vaccine is well positioned to fight the current strain of SARS-CoV-2 as well as the variants we're beginning to see."

"My research team and I as well as the entire Yerkes community are excited to move the Emory MVA COVID-19 vaccine forward," says Amara. "The world needs multiple COVID-19 vaccines to meet the demand. Our vaccine can stand alone as well as complement the available mRNA versions. It's a perfect combination of scientific expertise and collaboration, and commitment to improving human health."

Amara will continue his work on COVID-19 vaccines. One study focuses on the effectiveness of a single dose of the Emory MVA COVID-19 vaccine. A single dose could prove especially valuable to ensure vaccination compliance and, therefore, effectiveness, which can help drive a reduction in COVID-19 diagnoses and hospitalizations. Amara received two FastGrant awards to supplement his NIAID grant and expedite this follow-up COVID-19 research.

In a second study, Amara's team is focusing on inducing broader T cell responses capable of fighting new COVID-19 variants and other human coronaviruses. "The newly designed vaccines aim to induce T cells against multiple other genes of the virus in addition to targeting the spike protein," says Amara. "This requires inserting multiple genes of the coronavirus into the vaccine, which can be challenging. MVA, however, is well-suited for this because of its unique capacity to carry extra genes."

Credit: 
Emory Health Sciences

City, University of London academic tracks COVID-19 dark web marketplace before vaccine

image: Dr Andrea Baronchelli (City, University of London)

Image: 
(City, University of London)

New research carried out by City, University of London data scientist, Dr Andrea Baronchelli, and colleagues into the dark web marketplace (DWM) trade in products related to COVID-19, has revealed the need for the continuous monitoring of dark web marketplaces (DWMs) especially in light of the current shortage and availability of coronavirus vaccines.

In their paper, Dark Web Marketplaces and COVID-19: before the vaccine published in the EPJ Data Science, Dr Baronchelli and his colleagues analysed 851,199 listings extracted from 30 DWMs between January 1, 2020 and November 16, 2020 before the advent of the availability of the coronavirus vaccine.

They identify 788 listings directly related to COVID-19 products and monitors the temporal evolution of product categories including Personal Protective Equipment (PPE), medicines (e.g., hydroxychloroquine), and medical fraud.

The authors compare trends in the temporal evolution of trade in these products with variations in public attention, as measured by Twitter posts and Wikipedia page visits.

Among their discoveries, the paper's authors highlight the importance of dark web players such as DarkBay/DBay - the 'eBay of the dark web':

"In our dataset, DarkBay/DBay is featured prominently among DWMs offering COVID-19 specific listings. Ranking in the top 100 sites in the entire dark web, DarkBay/DBay is regarded as the eBay of the dark web because it offers more listings categories than other DWMs. It was also frequently accessible during the period of time monitored during this research, with an uptime of 80%, higher from the 77% uptime of Empire, the largest global DWM at the time of writing".

Critically, the authors highlight the importance of the continuous monitoring of DWMs, especially given shortages in the availability and supply of COVID-19 vaccines in various regions of the world:

"Uninformed citizens exposed to waves of misinformation, such as the ones related to hydroxychloroquine, chloroquine, and azithromycin, may be tempted to shop on DWMs thus exposing themselves to serious health risks. Moreover, the availability of regulated products currently in shortage in the traditional economy undermines anti-price gouging regulations and regulated businesses which sell the same products."

Credit: 
City St George’s, University of London

NANOGrav finds possible 'first hints' of low-frequency gravitational wave background

image: Sarah Burke-Spolaor

Image: 
West Virginia University

In data gathered and analyzed over 13 years, the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) Physics Frontiers Center (PFC) has found an intriguing low-frequency signal that may be attributable to gravitational waves.

NANOGrav researchers - including a number from West Virginia University's (WVU's) Department of Physics and Astronomy and the Center for Gravitational Waves and Cosmology - measure the times of arrival of radio pulses from exotic stars called pulsars with large radio telescopes, including the Green Bank Telescope (GBT) in Pocahontas County, West Virginia. Pulsars are small, dense stars that rapidly rotate, emitting beamed radio waves, much like a lighthouse. The results from this most recent dataset show perturbations in the arrival times from these pulsars that may indicate the effects of gravitational waves, as reported recently in The Astrophysical Journal Letters. The most likely source of these gravitational waves is the combined signal from all the supermassive black hole pairs at the cores of merged, distant galaxies.

NANOGrav has been able to rule out some effects other than gravitational waves, such as interference from the matter in our own solar system or certain errors in the data collection. These newest findings set up direct detection of gravitational waves as the possible next major step for NANOGrav and other members of the International Pulsar Timing Array (IPTA), a collaboration of researchers using the world's largest radio telescopes.

Dustin Madison, a postdoctoral researcher at WVU, comments "We can't yet say with confidence that what we're seeing is gravitational waves, but if it is, the "signal" makes a lot of sense given what we think we know about supermassive black holes. This was always how this was going to play out...enticing hints of a signal before we would be able to definitively claim a detection. We're on the right track to make that definitive assessment in just a couple of years." Looking to the future, he thinks researchers will then be able to characterize the signal and learn more from it for years and years to come.

Gravitational waves are ripples in space-time caused by the movements of incredibly massive objects, such as black holes orbiting each other or neutron stars colliding. Astronomers cannot observe these waves with a telescope like they do stars and galaxies. Instead, they measure the effects passing gravitational waves have, namely tiny changes to the precise position of objects - including the position of the Earth itself. Gravitational waves were first detected in 2015 by NSF's Laser Interferometer Gravitational-Wave Observatory (LIGO) by a team including other researchers at WVU. Like light from distant objects, gravitational waves are a cosmic messenger signal - one that holds great potential for understanding "dark" objects, like black holes.

NANOGrav chose to study the signals from pulsars because they serve as detectable, dependable Galactic clocks. These small, dense stars spin rapidly, sending pulses of radio waves at precise intervals toward Earth. Pulsars are in fact commonly referred to as the universe's timekeepers, and this unique trait has made them useful for astronomical study.

But gravitational waves can interrupt this observed regularity, as the ripples cause space-time to undergo tiny amounts of stretching and shrinking. Those ripples result in extremely small deviations in the expected times for pulsar signals arriving on Earth. Such deviations indicate that the position of the Earth has shifted slightly. By studying the timing of the regular signals from many pulsars scattered over the sky at the same time, known as a "pulsar timing array," NANOGrav works to detect minute changes in the Earth's position due to gravitational waves stretching and shrinking space-time.

WVU Professor and NANOGrav member Sarah Burke-Spolaor explains "This signal is incredibly enticing. It could be that our orchestra is tuning up, hinting that we're about to hear the grand symphony of waves from supermassive black holes that we expect pervades the Universe," Burke-Spolaor reflects. She adds, "If this signal is indeed gravitational waves, future study will offer unique insights into how the biggest black holes and galaxies in our universe form and evolve".

"NANOGrav has been building to the first detection of low frequency gravitational waves for over a decade and today's announcement shows that they are on track to achieving this goal," said Pedro Marronetti, NSF Program Director for gravitational physics. "The insights that we will gain on cosmology and galaxy formation are truly unparalleled."

NANOGrav is a collaboration of U.S. and Canadian astrophysicists and a National Science Foundation Physics Frontiers Center (PFC). Maura McLaughlin, WVU Professor and Co-Director of the NANOGrav PFC, added "We are so grateful for the support of the NANOGrav PFC, that's allowed us to dramatically increase both the number of pulsars being timed and the number of participants working on NANOGrav research over the past six years". WVU has played a significant role in the PFC; 12 of the 63 authors on this paper are WVU faculty, postdocs, and students. And low-frequency gravitational wave detection is one of the main aims of the Center for Gravitational Waves and Cosmology, formed in 2015 along with the award of the PFC. As, Duncan Lorimer, WVU Professor and Eberly College Associate Dean for Research, notes "The long-term institutional support provided by the College and University has played a critical role in NANOGrav's success since its inception in 2007".

NANOGrav created their pulsar timing array by studying 47 of the most stably rotating "millisecond pulsars" with both the GBT and the Arecibo Observatory in Puerto Rico as reported in the January 2021 Astrophysical Journal Supplements. Not all pulsars can be used to detect the signals that NANOGrav seeks - only the most stably rotating and longest-studied pulsars will do. These pulsars spin hundreds of times a second, with incredible stability, which is necessary to obtain the precision required to detect and study gravitational waves.

Of the 47 pulsars studied, 45 had sufficiently long datasets of at least three years to use for the analysis. Researchers studying the data uncovered a spectral signature, a low-frequency noise feature, that is the same across multiple pulsars. The timing changes NANOGrav studies are so small that the evidence is not apparent when studying any individual pulsar, but in aggregate, they add up to a significant signature.

Potential Next Steps

To confirm direct detection of a signature from gravitational waves, NANOGrav's researchers will have to find a distinctive pattern in the signals between individual pulsars. At this point, the sensitivity of the experiment is not currently good enough for such a pattern to be distinguishable. Boosting the signal requires NANOGrav to expand its dataset to include more pulsars studied for even longer lengths of time, which will increase the array's sensitivity. In addition, by pooling NANOGrav's data together with those from other pulsar timing array experiments, a joint effort by the IPTA may reveal such a pattern. Students and faculty at WVU are important contributors to this effort, and in fact 24 WVU students have traveled to IPTA partner countries to undertake research abroad as part of NSF-funded programs led by WVU.

At the same time, NANOGrav is developing techniques to ensure the detected signal could not be from another source. They are producing computer simulations that help test whether the detected noise could be caused by effects other than gravitational waves, in order to avoid a false detection.

While the next several years hold a great deal of scientific promise, they are not without challenges. With the recent collapse of the Arecibo Observatory's 305-meter telescope, NANOGrav will be seeking alternate sources of data and working even more closely with their international colleagues. Although significant delays in detection are not expected, due to years of very sensitive Arecibo data already contributing to their datasets, the loss of Arecibo is a terrible blow to science in general. For NANOGrav, it may impact the ability to characterize the background and detect other types of gravitational-wave sources in the future in the absence of another instrument. The loss of the telescope also directly impacts the graduate studies of several WVU PhD students. NANOGrav members are deeply saddened by the collapse and its impact on the staff and the island of Puerto Rico.

Credit: 
West Virginia University

New eco-friendly technique protects rice plants against devastating fungal infection

image: Spraying rice flowers with a non-pathogenic fusaria produces seeds carrying the non-pathogenic fusaria and controls seedborne bakanae disease.. disease

Image: 
Tsutomu Arie, Tokyo University of Agriculture and Technology

Researchers have developed a new technique to protect rice seeds against fungal infections that can ruin up to half of all rice crops in the world. The biocontrol method, which involves inoculation of flowers with a different fungus that doesn't cause disease and using seeds harvested from the flower to grow crops, is even better at protecting rice plants from diseases than existing fungicide approaches, and could also be used against similar pathogens that affect other staple crops.

The extremely destructive seedborne bakanae disease, which affects rice plants everywhere in the world that the staple crop is grown, is currently typically combatted with either chemical fungicides or by hot-water treatment of seeds, all of which face growing challenges to their effectiveness.

However, researchers have developed a new anti-bakanae technique that actively encourages the spread of a different, non-pathogenic variety of fungus, that has been shown to outcompete the disease-causing fungus on rice seeds. This biocontrol method not only delivers protection against bakanae disease as effectively as traditional methods, but can also prevent bakanae disease from affecting the seeds, which current techniques cannot.

The researcher's findings are reported in the journal Applied and Environmental Microbiology on January 4, 2021 and was selected as a spotlight paper (https://aem.asm.org/content/87/2/e02789-20).

The pathogenic fungus Fusarium fujikuroi produces gibberellic acid, a plant growth hormone, on rice plants and drives abnormal elongation and etiolation. The affected plants appear pale yellow or white, produce no edible grains, and suffer from weak stems that topple over, hence the name "bakanae," Japanese for "foolish seedling." Losses in the field are substantial wherever the disease emerges, but particularly severe in Asian countries, where the disease can hit 20-50% of crops.

Throughout agriculture, efforts to reduce conventional pesticide use are widespread in order to limit negative impacts on other organisms, but the additional problems that conventional methods of tackling bakanae disease face only add to the need to come up with an alternative. None of these techniques have been very stable, and thus lead to disease outbreaks. They are also not very efficient at combating deeply infected seed stocks. On top of this, existing chemical fungicides also increasingly face challenges from fungicide-resistant strains of the fungus.

The new biocontrol technique, developed by plant pathologists at Tokyo University of Agriculture and Technology, involves spraying rice flowers with a non-pathogenic strain of the fusaria fungus and produces rice seeds carrying the non-pathogenic fusaria. Testing against conventional techniques showed roughly the same level of effectiveness, both against transmission of the disease to seeds, but also transmission among offsprings.

"Investigation under the microscope suggests that the non-pathogenic strain out-competes its cousin, preventing the pathogenic fungi from colonizing the seed, while the growth of the 'good' fungus causes no harm," said Tsutomu Arie, professor and Hiroki Saito, graduate student at the Laboratory of Plant Pathology, Graduate School of Agriculture, Tokyo University of Agriculture and Technology.

As the spread of the good fungus appears to completely replace the bad fungus, the technique should also work on heavily affected seed stocks.

Because rice seeds are usually stored for about six months over the winter before sowing in Japan, the non-pathogenic fusaria in seeds needed to survive at least this amount of time. So to track how long the protection lasted, the researchers genetically tweaked the fungus to make them fluorescent. Six months later, microscopic investigations found that fungal mycelia were still fluorescent, demonstrating they were still there and out competing their "bad" fungus cousins.

The reproductive mechanics of other staple crops in the Poaceae family of grasses that the rice plant belongs to, such as wheat, barley and corn are similar enough that the technique could work on fungal infestations that affect these plants as well. The researchers now aim to test their new method on these crops, as well as on tomatoes, spinach, lettuce, and carrots.

Credit: 
Tokyo University of Agriculture and Technology

New combination therapy offers chance of healing hepatitis B

image: The digitally-colourized transmission electron microscopic image reveals the presence of Hepatitis B virions (orange coloured).

Image: 
CDC/Dr. Erskine Palmer

The new therapeutic approach is based on shutting down the viral hepatitis B genome located in the nucleus of infected liver cells. Upon infection of the liver cell, the viral genome is transformed inside the nucleus into a closed circular DNA molecule. This deoxyribonucleic acid is a stable molecule known as covalently closed circular DNA (cccDNA) and serves as the template for the production of new viruses. The cccDNA represents the central reservoir of the hepatitis B viruses and enables their persistence in the liver. The virologist Prof. Dr. Maura Dandri and her team at the UKE managed to prevent the HBV-cccDNA from producing further viruses in the animal model.

The point of attack of their therapy is the viral HBx protein, which protects the cccDNA in the cell nucleus from silencing by preventing a host factor (SMC complex) from binding to it. The team treated the animals on the one hand with the antiviral cytokine interferon-alpha, which was already shown to reduce viral RNA, and on the other they suppressed the formation of the HBx protein by RNA interference, a method in which the translation from RNA to protein is inhibited. In both cases, they were able to abrogate HBx production in most infected cells, and thus to deactivate the cccDNA through reappearance of the host restriction factor. In addition, they combined this treatment with the administration of bulevirtide, able to prevent the entry of HBV into the cells and thus a reinfection. In this way, the effect of the cccDNA deactivation could be maintained even beyond the end of treatment. Bulevirtide, better known by the research name myrcludex, was co-developed in the DZIF and has recently been approved for the European market as an active substance in the treatment of hepatitis D.

"This combination therapy was able to achieve the sustained shutting down of the cccDNA in infected cells," Prof. Dandri explains. She directs the "HBV Cure" project in the DZIF and the "Virushepatitis" working group in the UKE. Even though it has as yet only been tested in the mouse model, Prof. Dandri is convinced of the combination: "The results show that the HBV genome can be shut down with certain combination treatments. These approaches can now be applied in clinical studies in order to achieve a functional cure of chronic hepatitis B."

Credit: 
German Center for Infection Research

Horse remains reveal new insights into how Native peoples raised horses

image: Study coauthor Isaac Hart of the university of Utah compares a healthy talus bone from the Lehi horse with one heavily impacted by arthritis.

Image: 
William Taylor

A new analysis of a horse previously believed to be from the Ice Age shows that the animal actually died just a few hundred years ago--and was raised, ridden and cared for by Native peoples. The study sheds light on the early relationships between horses and their guardians in the Americas.

The findings, published today in the journal American Antiquity, are the latest in the saga of the "Lehi horse."

In 2018, a Utah couple was doing landscaping in their backyard near the city of Provo when they unearthed something surprising: an almost complete skeleton of a horse about the size of a Shetland pony. Scientists and the media took note. Preliminary data suggested that the horse might be more than 10,000 years old.

"It was found in the ground in these geologic deposits from the Pleistocene--the last Ice Age," said William Taylor, lead author of the new research and a curator of archaeology at the CU Museum of Natural History at the University of Colorado Boulder.

Based on a detailed study of the horse's bones and DNA, however, Taylor and his colleagues concluded that it wasn't an Ice Age mammal at all. Instead, the animal was a domesticated horse that had likely belonged to Ute or Shoshone communities before Europeans had a permanent presence in the region.

But Taylor is far from disappointed. He said the animal reveals valuable information about how Indigenous groups in the West looked after their horses.

"This study demonstrates a very sophisticated relationship between Indigenous peoples and horses," said Taylor, also an assistant professor in the Department of Anthropology. "It also tells us that there might be a lot more important clues to the human-horse story contained in the horse bones that are out there in libraries and museum collections."

Written in bone

Taylor leads an effort funded by the U.S. National Science Foundation, called "Horses and Human Societies in the American West." And he's something akin to a forensic scientist--except he studies the remains of ancient animals, from horses to reindeer. He said that researchers can learn a lot by collecting the clues hidden in bones.

"The skeleton that you or I have is a chronicle of what we've done in our lives," Taylor said. "If I were to keel over right now, and you looked at my skeleton, you'd see that I was right-handed or that I spend most of my hours at a computer."

When Taylor first laid eyes on the Lehi horse in 2018, he was immediately skeptical that it was an Ice Age fossil. Ancient horses first evolved in North America and were common during the Pleistocene, he said, going extinct at about the same time as many other large mammals like mammoths. This horse, however, showed characteristic fractures in the vertebrae along its back.

"That was an eyebrow raiser," Taylor said.

He explained that such fractures often occur when a human body bangs repeatedly into a horse's spine during riding--they rarely show up in wild animals, and are often most pronounced in horses ridden without a frame saddle. So he and his colleagues decided to dig deeper.

DNA analyses by coauthors at the University of Toulouse in France revealed that the Lehi horse was a roughly 12-year-old female belonging to the species Equus caballus (today's domestic horse). Radiocarbon dating showed that it had died sometime after the late 17th century. The horse also seemed to be suffering from arthritis in several of its limbs.

"The life of a domestic horse can be a hard one, and it leaves a lot of impacts on the skeleton," Taylor said.

He added that scientists originally believed that the horse was so ancient in part because of its location deep in the sands along the edge of Utah Lake: Its caretakers appear to have dug a hole and intentionally buried the animal after it died, making it look initially as if it had come from Ice Age sediments.

And despite the animal's injuries, which would have probably made the Lehi horse lame, people had continued to care for the mare--possibly because they were breeding her with stallions in their herd.

Hidden history

For Carlton Shield Chief Gover, a coauthor of the new study, the research is another example of the buried history of Indigenous groups and horses.

He explained that most researchers have tended to view this relationship through a European lens: Spaniards brought the animals to the Americas on boats, and white settlers shaped how Native peoples interacted with them.

But that view glosses over just how uniquely Indigenous the horse became in the Americas after those first introductions.

"There was a lot going on that Europeans didn't see," said Shield Chief Gover, a graduate student at CU Boulder and a tribal citizen of the Pawnee Nation. "There was a 200-year period where populations in the Great Plains and the West were adapting their cultures to the horse."

For many Plains groups, horses quickly changed nearly every aspect of life.

"There was more raiding and fewer battles," Shield Chief Gover said. "Horses became deeply integrated into Plains cultures, and changed the way people moved, traded hunted and more."

He and Taylor hope that their research will, alongside Indigenous oral traditions, help to shed light on those stories. Taylor, for his part, suspects that the Lehi horse may not be the only set of remains mistakenly shelved with Ice Age animals in museum collections around the country.

"I think there are a lot more out there like this," he said.

Credit: 
University of Colorado at Boulder

In Ethiopia, mother's wealth more protective against child marriage than father's

For a girl in Ethiopia, her mother's wealth can protect her from becoming a child bride - but if a father prefers child marriage, his own wealth may increase the likelihood that she will be married before 18, according to a Rutgers University-New Brunswick study.

Published in the journal World Development, the study found that girls whose mothers have more asset holdings - a cellphone, bicycle, sewing machine, jewelry or other valuables - have a reduced rate of entering into a child marriage, while the rate is higher for girls whose fathers have more asset holdings.

"Child marriage is concerning from a human rights, health and economic perspective," said the study's author Felix Muchomba, assistant professor at the Rutgers School of Social Work. "Girls married before age 18 are more likely to drop out of school early, become poor, acquire sexually transmitted infections, experience domestic violence, teenage childbirth and accompanying childbirth complications, including low birth weight babies or death."

In Ethiopia, where the study was conducted, about a quarter of girls are married by age 15 and more than half are married by 18. The researchers found that the median age of marriage for girls whose mothers were in the bottom 25 percent in terms of asset holdings was 16.6 years - 1.2 years lower than girls whose mothers were in the top 25 percent.

The findings indicate that mothers may be less likely to prefer child marriage for their daughters, and more acutely aware of their daughters' opposition to child marriage - and that wealthier mothers are in a better position to protect their daughters by leveraging their increased bargaining power.

The study noted that fathers may prefer child marriage because of gender norms that assign them the responsibility of arranging marriages. Fathers may also be more aware that a daughter's marriage prospects would be ruined if her reputation of sexual purity was tarnished or if she got older, which pressures fathers to marry daughters off early.

The findings are significant, Muchomba says, because they can help in international efforts - such as improving women's economic positions - to prevent child marriage. Child marriage, he says, determines whether a girl will be able to finish high school and whether she will be a child when she starts having children.

"It is estimated that, globally, 14 million girls are married before age 18 each year," said Muchomba. "The United Nations Children's Fund has warned that the number of new child brides each year is projected to continue increasing and, in some parts of the world, the number of women married as children is expected to double by 2050 because of the persistence of the practice and population growth."

Credit: 
Rutgers University

School gardens linked with kids eating more vegetables

image: Children who learn to garden and cook in the TX Sprouts program led by researchers at The University of Texas at Austin were found to consume more vegetables.

Image: 
The University of Texas at Austin

Getting children to eat their vegetables can seem like an insurmountable task, but nutrition researchers at The University of Texas at Austin have found one way: school gardens and lessons on using what's grown in them.

Researchers worked with 16 elementary schools across Central Texas to install vegetable gardens and teach classes to students and parents about nutrition and cooking. In a study recently published in the International Journal of Behavioral Nutrition and Physical Activity, the team describes specifically targeting schools with a high percentage of students on the free and reduced-price lunch program to understand how nutrition programs affect low-income groups. Each school was studied for one academic year.

The study found that students who participated in the gardening, nutrition and cooking classes ate, on average, a half serving more vegetables per day than they did before the program.

"A lot of the families in these schools live with food insecurity. They live in food deserts and face a higher risk of childhood obesity and related health issues," said Jaimie Davis, associate professor of nutritional sciences at UT Austin and the lead author of the paper. "Teaching kids where their food comes from, how to grow it, how to prepare it -- that's key to changing eating behaviors over the long term."

In addition to tracking what the children ate, the study looked at weight, body mass index and blood pressure. During the nine months of the study, there were no statistically significant changes in those measures of health. The study involved more than 3,000 students in the third through fifth grades.

Although a half serving increase in vegetable consumption per day may seem like a small change, it's extremely encouraging to Davis and her colleagues.

"Behavior changes can be difficult to achieve, especially long term," Davis said. "Changes to health parameters like blood pressure may take longer to manifest. Getting children to eat more vegetables can potentially set them up for long-term success."

Previous studies have shown that increased fruit and vegetable consumption can promote health and lower the risk of developing cardiovascular disease, type 2 diabetes and some cancers. More fruits and vegetables may play a role in reduced obesity in adults, but the effects have not been well studied in children.

"We have been able to introduce children to a wide variety of vegetables that they've never had access to," Davis said. "Parents I talk with ask, 'How did you get my kid to eat kale?' But when they grow the kale from seed and learn how to prepare it in olive oil and bake it into kale chips, they love it."

Credit: 
University of Texas at Austin

Songbirds exposed to lead-contaminated water show telltale signs about human impacts

image: A male zebra finch displaying its bright red beak and orange cheek patches in the wild.

Image: 
Photo courtesy of Adobe Stock / Xavier MARCHANT

Humans, wildlife, and the environment are all interconnected and play a role in one another's health and well-being. Sentinel species, such as birds, are good indicators of environmental health, and they can send subtle warning signs that humans may be in danger next.

In an experimental exposure study, Kendra Sewall, an associate professor of biological sciences in the College of Science, and a diverse team of scientists and students have found that lead levels like those reported in Flint, Michigan, can interfere with the neural mechanisms of vocal development of songbirds and affect mate attraction.

By examining the effects of lead exposure in songbirds, more information will be known about how lead impacts learning and underlying neural networks in humans, since they share the same critical period of vocal learning.

"Our study shows that levels of lead in water that are known to be concerning for human health also have negative effects on the brain and the learning ability of male songbirds and compromises their ability to attract a mate," said Sewall, an affiliated faculty member of the Fralin Life Sciences Institute and the Global Change Center.

Their findings were published in Ecotoxicology and Environmental Safety on Jan. 8.

Lead is a heavy metal. When ingested, lead competes with calcium, a nutrient that is crucial for brain growth, muscle function, and neural function. For that very reason, the Center for Disease Control and the World Health Organization consider any detectable amount of lead in blood to be dangerous for children and animal health.

One process is particularly vulnerable to lead exposure: vocal learning, a trait shared by humans and songbirds. This is because this form of learning occurs at an early age, when the brain is undergoing a significant amount of growth and reorganization.

For this particular study, researchers studied male zebra finches. These small, highly social songbirds from the wilds of Australia are an excellent model for how humans learn speech. Not only do zebra finches learn their songs in the same way that we do, but they also have brain areas that are analogous to our vocal learning brain regions.

"Early in life, humans and songbirds have to hear adult vocalizations that they memorize and practice until their vocalizations are perfected," said Sewall. "If songbirds or humans are deprived of an adult model, or if their learning process is impeded by environmental challenges like lead contamination, they won't be able to produce normal vocalizations."

In order to show that this model system can be relevant to humans and our health, researchers had to determine if birds metabolize lead in the same way human children do. Sewall and her colleagues studied young male zebra finches that had been exposed to 1,000 parts per billion of lead in their drinking water, which is comparable to the highest levels that have been reported in Flint, Michigan, and measured the resulting amount of lead in their blood and brain tissue.

They found that males that had ingested the contaminated water had lead blood levels ranging from 2.6 to 6.8.

"The blood levels are concerning, but below what would trigger any major intervention if these were human blood levels," said Sewall. "Yet these blood levels adversely affected the brain and learning in these young birds. This highlights the fact that lead can be really dangerous and that we are probably ignoring levels of lead in blood and in the environment that could be causing damage to humans and animals alike."

To learn as much as they could from this study, researchers looked at additional physiological endpoints, including other aspects of learning, male coloration, and the ability of males to attract female attention.

Male songbirds who were exposed to lead produced poorer quality songs compared to the control males. Upon further inspection, researchers also found that their brains had smaller song-learning nuclei, or clusters of neurons in the central nervous system.

In addition to poor song quality, lead treated males also had differences in coloration. Male zebra finches use dances, cheek patches, and bright bills to attract females. The lead exposed males had cheek patches with less hue and red saturation than the control males.

Due to poorer song quality and dull coloration, females showed less preference for the lead-treated males, and the male's ability to attract a mate was compromised. This finding, in particular, raises the possibility that male birds exposed to environmental toxicants could have reduced reproductive success. However, it is unclear if this could have negative effects on reproduction and persistence of wild songbird populations.

Historically, research has been heavily focused on the short-term consequences of high environmental toxicant levels, rather than the long-term consequences of prolonged exposure to low levels of environmental pollutants.

"We have known for years that animals like the California condor are at risk of death from eating animals killed with lead shot," said Sewall. "Our study suggests that wild animals exposed to low levels of lead could have reduced reproduction, which is a concern for maintaining healthy wild populations. I'm reminded of a quote from Rachel Carson's 'Silent Spring,' 'but man is a part of nature, and his war against nature is inevitably a war against himself.'"

Moving forward, Sewall and the team will study the mechanism by which these low levels of lead can impair learning and indirectly impair the reproductive success of songbirds. Collaborator and Global Change Center affiliate, Chris Thompson, an assistant professor at Virginia Tech's School of Neuroscience, will be assisting with studies examining exactly how lead interferes with neural growth and causes neural damage.

"Despite knowing for many decades that lead is toxic, especially during early development, much remains unknown about the precise mechanisms by which it disrupts the brain and resulting functional outcomes such as communication," said William Hopkins, director of the Global Change Center. "The work being conducted by Sewall and her colleagues will shed light on this pervasive environmental issue that continues to have widespread adverse effects on the health and behavior of both humans and wildlife."

Sewall will also be working with Jamie Cornelius, an assistant professor at Oregon State University who is studying blood lead levels in songbirds living in parks in and around Flint, Michigan. Sewall's team will pursue more behavioral and physiological testing of wild birds at these sites.

Christopher Goodchild, an assistant professor of biology at the University of Central Oklahoma, was the first author on the paper. Michelle Beck, an assistant professor of biology at Rivier University; Sam Lane and Isaac VanDiest, who are graduate students in the Department of Biological Sciences and in the Interfaces of Global Change IGEP; and Frankie Czesak, an undergraduate Neuroscience Fellow; were all co-authors. All of their expertises and hard work were critical to the findings of this study.

"For this project, it was really critical to get all of the information that we possibly could from these birds," said Sewall. "We looked at consequences of lead exposure in water for several physiological endpoints, neurological outcomes, and learning and behavior. So, having different people who can spearhead each component of the study was really important."

Credit: 
Virginia Tech

COVID-19 health threat increases psychological distress among Black Americans

As the coronavirus pandemic continues to devastate communities worldwide, Black Americans who face racial discrimination in hospitals and doctor's offices weather additional stresses that can exacerbate threats from COVID-19. A new University of Georgia study examines the interplay between the perceptions of coronavirus threat and psychological distress among Black Americans.

The additional stresses arise from the prevalent belief among Black Americans worried that they might not recover from how hospitals treat them if they become infected with the coronavirus.

"While the notion has been floated among commentators, this is the first study that uses nationally representative data to assess whether this threat, or feeling, is real among Black adults, and then assess how it how it impacts their health," said Ryon Cobb, assistant professor of sociology in the UGA Franklin College of Arts and Sciences and lead author on the study.

The study used data from the American Trends Panel survey by the Pew Research Center collected shortly after the initial outbreak in March 2020, a nationally representative sample of adults in the United States.

Using self-reports of perceived coronavirus threat and beliefs about racism in medical settings, researchers found that the perception that the coronavirus outbreak was a major threat to one's health and the belief that Black Americans face discrimination in medical settings were positively and significantly associated with higher psychological distress levels.

The research also establishes a relationship between these two factors that multiply the risk. Cobb said the data suggest people may take preventive measures more seriously though it could also cause Black adults to engage less with the health care system.

"What we find in the data is the more people think COVID-19 outbreak is a threat to their health, it increases the likelihood of adherence, with Blacks and Latinos more likely to adhere to COVID guidelines than their white counterparts," he said.

The study identifies the additional effect of the outbreak's psychological impacts on these groups, beyond the threat of contracting the virus. "Contracting COVID-19 makes interactions with the health care system inevitable. The fear held by many people of color is that medical institutions are biased against Blacks. The stress of the outbreak and potentially unfair treatment appears to induce psychological distress," said Christy L. Erving, assistant professor in the Department of Sociology at Vanderbilt University.

"Discussions about dealing with the fear of just getting it or not often come down to, if you don't get it, you're fine," Cobb said. "But the outbreak itself is stressful, and the increasing stress is part of people's health, regardless of whether they have COVID."

The study presents a snapshot of some underlying aspects of how structural bias in the American health care system contributes to the outbreak's stressfulness, which continues to have a disproportionate effect on Black Americans.

"These findings highlight the complexity of how a public health crisis can influence Black community members' navigation of an already unequal health care system in increasingly difficult circumstances," W. Carson Byrd, associate professor at the University of Michigan, added.

"We need to be mindful of these perceptions, especially as they blend with the reality that, in the United States, hospitals are businesses. As such, their profits track with the severity of illness in patients. While the stories are anecdotal, they are also backed up by the data: People being turned away from hospitals or unable to see a doctor can lead to worsening health," Cobb said.

"And by the time things are critical, at least for Black Americans, the perception is that there is little hope for recovery."

Credit: 
University of Georgia

Study reveals how air pollution may increase the risk of cardiovascular disease

BOSTON - Tiny particles of air pollution -- called fine particulate matter -- can have a range of effects on health, and exposure to high levels is a known risk factor for cardiovascular disease. New research led by investigators at Massachusetts General Hospital (MGH) reveals that fine particulate matter has a detrimental impact on cardiovascular health by activating the production of inflammatory cells in the bone marrow, ultimately leading to inflammation of the arteries. The findings are published in the European Heart Journal.

The retrospective study included 503 patients without cardiovascular disease or cancer who had undergone imaging tests at MGH for various medical reasons. The scientists estimated participants' annual average fine particulate matter levels using data obtained from the U.S. Environment Protection Agency's air quality monitors located closest to each participant's residential address.

Over a median follow-up of 4.1 years, 40 individuals experienced major cardiovascular events, such as heart attacks and strokes, with the highest risk seen in participants with higher levels of fine particulate matter at their home address. Their risk was elevated even after accounting for cardiovascular risk factors, socioeconomic factors, and other key confounders. Imaging tests assessing the state of internal organs and tissues showed that these participants also had higher bone marrow activity, indicating a heightened production of inflammatory cells (a process called leukopoiesis), and elevated inflammation of the arteries. Additional analyses revealed that leukopoiesis in response to air pollution exposure is a trigger that causes arterial inflammation.

"The pathway linking air pollution exposure to cardiovascular events through higher bone marrow activity and arterial inflammation accounted for 29% of the relationship between air pollution and cardiovascular disease events," says co-first author Shady Abohashem, MD, a cardiovascular imaging fellow at MGH. "These findings implicate air pollution exposure as an underrecognized risk factor for cardiovascular disease and suggest therapeutic targets beyond pollution mitigation to lessen the cardiovascular impact of air pollution exposure."

Co-first author Michael Osborne, MD, a cardiologist at MGH, explains that therapies targeting increased inflammation following exposure to fine particulate matter may benefit patients who cannot avoid air pollution. "Importantly, most of the population studied had air pollution exposures well below the unhealthy thresholds established by the World Health Organization, suggesting that no level of air pollution can truly be considered safe," he says.

Credit: 
Massachusetts General Hospital

CU offers plan for improving mental health care for resident physicians

A pilot program to offer mental health services offered resident physicians at the University of Colorado School of Medicine provides a model for confidential and affordable help, according to an article published today by the journal Academic Medicine.

For the 2017-2018 class, 80 resident physicians in the internal medicine and in internal medicine-pediatrics programs were enrolled in a mental health program that provided scheduled appointments at the campus mental health center. Residents were allowed to opt-out of the appointments. The cost of the appointments was covered by the residency programs, not charged to residents. Programs received de-identified invoices so that residents who participated could receive care confidentially.

"Developing mental health programs for residents can be challenging, as previous research has revealed that lack of time, concerns about confidentiality, concerns about stigma, and cost are significant barriers to residents seeking mental health care," the authors write.

Concerns about mental health for health care workers, and resident physicians in particular, have been elevated in in recent years as studies have identified the prevalence of burnout and depression. The authors explain that unaddressed mental health concerns among resident physicians can have a direct impact on patient care.

Of the 80 resident physicians who were automatically enrolled for mental health services in the pilot program, 23 attended the scheduled appointments, 12 were no-shows, and 45 opted out. Forty-one of the 80 resident physicians responded to an anonymous post-appointment survey. Among the survey respondents were 16 who attended their mental health appointments. Survey respondents, even those who opted out, were mostly appreciative of the program.

While the number of residents participating in the study is relatively small, the authors write that the "mental health program positively influenced the well-being of residents by demonstrating that the residency program was 'walking the walk' and not simply 'talking the talk' with regard to wellness."

Credit: 
University of Colorado Anschutz Medical Campus

Uncovering a link between inflammation and heart disease

Inflammation is supposed to help protect us--it's part of an immune response to fight off pathogens and clear infections. But patients with cardiac disease often have chronic inflammation that damages their hearts, even with no infection present.

In a recent study published in Circulation, immunologists at Tufts University School of Medicine in collaboration with investigators at Vanderbilt University and Tufts Medical Center revealed a mechanism that is activating T cells, a type of immune cell, and causing inflammation in the heart.

"Not all inflammation is the same," says Pilar Alcaide, a Kenneth and JoAnn G. Wellner Professor at Tufts School of Medicine and corresponding author on the study. "We really need to investigate the immunological aspects of the heart and other organs to try to be specific about targeting disease."

When a heart attack or other issue damages the heart and leaves it unable to pump enough blood to meet the body's needs, the heart tries to compensate by pumping faster. The cardiac muscle cells have to work harder and this stress causes them to release molecules known as reactive oxygen species.

Looking at the hearts of mice, the researchers determined that products of these reactive oxygen species modify proteins in the heart so that the immune system views them as a potential threat.

"The formation of these new targets is what we found that our T cells are robustly responding to," says Jay Ngwenyama, a postdoctoral scholar in Alcaide's lab and lead author on the study. "And this ultimately leads to inflammation that affects the heart."

The researchers confirmed that these modified proteins also appeared in the cardiac tissue of human patients whose hearts were failing.

Chronic inflammation can cause structural changes to the heart--the muscle can become enlarged or develop fibrous tissue, impeding its ability to pump blood efficiently and leading to further deterioration. But anti-inflammatory treatments or attempts to broadly target reactive oxygen species have yet to be successful, Ngwenyama says. They often end up interfering with other aspects of the immune system or necessary physiological processes.

With this improved understanding of how T cells are being activated in patients with heart disease, the researchers hope to develop more targeted treatments. They have already tested one possibility in mice: an agent that binds to the specific molecules altering cardiac proteins.

"We were actually able to prevent the inflammation and cardiac dysfunction that typically occur," Ngwenyama says. "So we're hoping that down the road this could have some significant implications in terms of treating humans for heart failure."

Credit: 
Tufts University, Health Sciences Campus

Dementia-related psychosis: GSA experts identify ways to improve care

A new white paper from The Gerontological Society of America (GSA) highlights the variety of challenges that persons with dementia-related psychosis and their caregivers have encountered during moves through different health care settings -- and proposes strategies to address these challenges.

It is estimated that over 2 million Americans with dementia experience delusions (false beliefs) and hallucinations (seeing or hearing things that others do not see or hear). This group of symptoms, known as dementia-related psychosis, frequently goes undetected in people who may be struggling with other complex behavioral and psychological symptoms of dementia.

The white paper, "Dementia-Related Psychosis: Strategies to Address Barriers to Care Across Settings," was developed by a clinical workgroup of experts whose membership reflects multiple areas of expertise, including primary care, neurology, psychiatry, and nursing. It follows a 2019 GSA publication, "Dementia-Related Psychosis: Gaps and Opportunities for Improving Quality of Care."

"When left untreated, the hallucinations and delusions that frequently occur in patients with dementia can cause significant patient and caregiver distress and often lead to institutionalization," said Gary W. Small, MD, FGSA, who chaired the workgroup. "There is a pressing need for greater awareness of the condition and more effective diagnostic and treatment strategies."

Small is the chair of psychiatry at Hackensack University Medical Center and the physician in chief of behavioral health at Hackensack Meridian Health.

According to the white paper, psychosis in dementia is associated with an increased risk of recurrent hospitalization and the need for more restrictive levels of care. Better care of individuals with dementia-related psychosis requires new initiatives and advocacy at several levels.

"Primary care needs full support to be able to better identify and care for these patients, both in terms of education about dementia-related psychosis and its management, and also by providing enhanced access to expert and specialty care, particularly for providers in rural communities," said Alexis Eastman, MD, who also served on the workgroup. "We need to not only formalize and expand the education of trainees and providers on this disease, but enhance care coordination opportunities through collaborative models and telehealth platforms -- to ensure that providers not only have understanding of dementia-related psychosis, but the resources to adequately care for these patients."

Eastman is the medical director in the Division of Geriatrics at UW Hospitals and Clinics and an assistant professor at the University of Wisconsin School of Medicine and Public Health.

The white paper indicates that because patients with dementia-related psychosis who transition across settings of care may be at risk for worsening symptoms, such transitions should occur only when mandatory and be carefully managed by health care professionals who have experience specific to the care of persons with dementia. In long-term care settings, team-based approaches to care and additional education for staff, as well as surveyors, could help enhance resident quality of life and support guideline-based care.

Credit: 
The Gerontological Society of America

Food allergies are more common among Black children

Black children have significantly higher rates of shellfish and fish allergies than White children, in addition to having higher odds of wheat allergy, suggesting that race may play an important role in how children are affected by food allergies, researchers at Ann & Robert H. Lurie Children's Hospital of Chicago, Rush University Medical Center and two other hospitals have found.

Results of the study were published in the February issue of the Journal of Allergy and Clinical Immunology: In Practice.

"Food allergy is a common condition in the U.S., and we know from our previous research that there are important differences between Black and White children with food allergy, but there is so much we need to know to be able to help our patients from minority groups," said Mahboobeh Mahdavinia, MD, PhD, who is first author of the study and chief of the Division of Allergy and Immunology at the Medical Center. "In this current paper, our goal was to understand whether children from different races are allergic to similar foods, or if there is a difference based on their racial background."

Findings are a part of a large, multicenter national trial, called Food Allergy Management and Outcomes Related to White and African American Racial Differences (FORWARD), which aims to explore potential racial differences and disparities in food allergy outcomes including healthcare utilization, allergic reaction manifestation, management practices, and psycho-social outcomes.

"Previous studies indicate that cockroach exposure may be an important mechanism by which children develop a shellfish allergy. The immune system can confuse certain proteins in seafood with similar proteins that are present in the muscles of cockroaches that commonly elicit an allergic response," said Mahdavinia. "For example, research has suggested that shellfish allergy may occur from inhaling tropomyosin, the protein of two common household allergens, dust mite and cockroach, which share 80% of amino acid sequencing with shellfish. Tropomyosin, which regulates muscle contraction and relaxation, also has been found in fin fish."

Food allergy is a major public health concern, affecting 8% of children in the United States, with an estimated economic burden of $24.8 billion annually. For people with food allergies, eating a tiny amount of food can trigger symptoms such as hives, breathing, digestive problems, and/or anaphylaxis (a severe, potentially fatal allergic reaction).

"National surveys have shown that the prevalence of food allergy in general has been increasing in children in the U.S. among all races/ethnicities. However, much remains unknown about why certain allergies are more likely to affect children of particular races and ethnicities and how those racial/ethnic minority patients are affected," said the lead principal investigator of the study and senior author Ruchi Gupta, MD, MPH, Director of the Center for Food Allergy and Asthma Research at Northwestern University Feinberg School of Medicine and a physician at Ann & Robert H. Lurie Children's Hospital of Chicago.

Gupta, Mahdavinia, and colleagues are conducting a large study of children ranging in age from birth to 12 years old who are diagnosed with food allergy and were seen in allergy/immunology clinics at four urban tertiary care centers in the U.S., which include Rush University Medical Center, Ann & Robert H. Lurie Children's Hospital of Chicago, Cincinnati Children's Hospital Medical Center, and Washington D.C.'s Children's National Hospital. The study included 664 children and was composed of 36 percent non-Hispanic Black and 64 percent non-Hispanic White children.

While scientists are still trying to figure out the exact mechanism of the allergy, the findings provide further insight into the importance of reducing Black children's exposure to cockroaches.

"This information can help us care for not only a child's food allergy, but all of their allergic diseases, including asthma, allergic rhinitis, and atopic dermatitis," said Susan Fox, PA-C, MMS, who is a co-author of the study and an allergy and immunology physician assistant at Rush University Medical Center.

In this study, the Black children with food allergies were more likely to have asthma. The study also showed that children with a shellfish allergy were more likely to have more severe asthma, while other food allergens were not associated with a diagnosis of asthma.

"A major concern is that there is a higher prevalence of asthma in Black children with food allergies when compared with White children with food allergies. Approximately 70% of fatal food anaphylaxis is accompanied by asthma. Black children are at a two- to threefold risk of fatal anaphylaxis compared to White children," Mahdavinia said. "By knowing this information, it can identify patients most at risk.

"We need to conduct further research to identify food allergies and food sensitivities among all races and ethnicities so we can develop culturally-sensitive and effective educational programs to improve food allergy outcomes for all children," Mahdavinia added.

Credit: 
Ann & Robert H. Lurie Children's Hospital of Chicago