Focus on cities will boost benefits of air pollution action for most vulnerable

IMPERIAL COLLEGE LONDON

Meeting UK air pollution targets by focussing on urban areas will maximise health benefits for the most deprived communities.

A study led by Imperial College London researchers shows that reducing typically urban sources of fine-particle air pollution like roads, wood burners, and machinery would also reduce inequalities in how different communities suffer the health impacts.

Air pollution can reach the lungs, causing short-term irritation and more harmful long-term impacts on heart and lung function. For people with existing conditions like heart failure and asthma, this can worsen already serious health problems.

Residents or workers in more deprived areas are more likely to suffer these conditions, and as such are  disproportionately impacted by air pollution.

The new study shows that while there are many ways to reduce the UK population’s exposure to air pollution overall, focusing on these typically urban sources benefits deprived areas more, reducing the health inequalities across the country. The research is published in Environmental Advances.

Lead researcher Dr Huw Woodward, from the Centre for Environmental Policy at Imperial College London, said: “People facing higher air pollution in deprived areas suffer health inequalities, which have a profound impact on their quality of life. Reducing air pollution will benefit everyone, but thinking more deeply about how we get there can also help us alleviate the impact on the most vulnerable in society.”

Reducing bias

There are several types of air pollution, including nitrous dioxide and fine particles. This study focused on a type of fine-particle pollution called PM2.5 (pollution particles that are less than 2.5 microns across).

The UK Environment Act of 2021 set a target for cutting the population’s exposure to PM2.5 by 35% by 2040, compared to 2018 levels. In practice, this means reducing the sources of the pollution, which include industry, road transport, energy production and agriculture.

Experts and policymakers use models to explore different ways of reaching the target by reducing pollution from these sources by different proportions. While all reductions in pollutant emissions will reduce the population’s exposure, previous studies have not considered how different ways of reaching the target would influence the health inequality.

To track how different scenarios impact the inequality, the team created a new metric, called the Indicator of Exposure Bias (IoEB). They paired this with the UK Integrated Assessment Model, used to investigate the impact of future emissions scenarios on air quality in England.

The team modelled several of these scenarios, including two that meet the 2040 target, and used the IoEB to assess their impact on the exposure bias. The ‘successful’ scenarios both achieved the target by reducing PM2.5 sources from all sectors, but one focused more on urban sources, including road transport and wood burners.

While both these scenarios reduced the exposure bias, the one focusing more on urban sources had a larger impact, reduced the bias by 59% (compared to 43% for the other scenario).

North-South divide

There is also a bias between Southern and Northern areas of England, with the former experiencing higher levels of PM2.5 air pollution. This bias is due to the south receiving a greater proportion of pollution from shipping channels and continental neighbours. The south of England has fewer deprived areas than the north, and as such this north-south divide in PM2.5 from non-UK sources reduces the overall bias towards deprived areas.

Despite this, deprived areas still experience higher levels of PM2.5­ pollution. Of the sources under English control, the bias towards deprived areas is greater than that assessed by considering all sources including those from outside of the UK.

The study looked at pollution on the level of populations, as individual exposure is very difficult to estimate accurately.

The team believe their new measure can be applied to different countries or regions using models that estimates population exposure and socio-economic status. This could allow policymakers to identify the sectors which contribute disproportionately to the bias in exposure and to identify effective strategies for reducing this bias.

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JOURNAL

Environmental Advances

DOI

10.1016/j.envadv.2024.100529 

ARTICLE TITLE

Assessing PM2.5 exposure bias towards deprived areas in England using a new indicator

Novel mobile air monitoring technology yields greater insight into post-disaster pollution levels

Study was the first to apply the method to a real-world disaster—a major industrial fire in Indiana

TEXAS A&M UNIVERSITY

A team including researchers from the Texas A&M University School of Public Health and School of Medicine has found that high resolution mass spectrometry could be a valuable tool for identifying and assessing air-borne contaminants produced by natural and man-made disasters. Their findings were published in the Journal of Exposure Science & Environmental Epidemiology.

The scientists used high resolution mass spectrometry—a highly accurate means of identifying molecular compounds in a sample—in fall 2023 to identify volatile organic compounds (VOCs) present following a major fire that occurred on April 11, 2023, in Richmond, Indiana. The fire and subsequent explosions at the My Way plastic recycling plant led to the evacuation of residents in a half-mile radius from the facility. The fire was sufficiently large to be captured in satellite images, and debris was found as far away as Oxford, Ohio, nearly 30 miles from the site.

“The Environmental Protection Agency does extensive, long-term recovery work after disasters like this,” said researcher Natalie Johnson, PhD, from the Department of Environmental & Occupational Health. “We believe that our study proves this method produces accurate data very quickly, which could help officials determine the best evacuation zones following a disaster.”

The research was funded by the National Institute of Environmental Health Sciences. Others on the team were Eva C.M. Vitucci, PhD, a postdoctoral student in the Department of Environmental and Occupational Health, Carolyn L. Cannon, MD, PhD, from the Texas A&M School of Medicine and two colleagues from Carnegie Mellon University.

The team monitored the air within and bordering the half-mile evacuation zone using high resolution mass spectrometry and non-targeted analysis, a relatively new computational tool for detecting and identifying chemicals in environmental exposures.

Johnson said this approach is an improvement over the ones currently used in the field, which frequently have issues with instrument sensitivity, time limitations in sampling and ability to characterize a broad range of pollutants. Non-targeted analysis, on the other hand, quickly and effectively identifies all the compounds—even those not known to be present initially. While this approach has shown promise in previous tests, this was the first time it was applied to a real-world disaster.

After receiving training and guidance on the Hzard Comparison Module by Antony Williams of US-EPA’s Center for Computational Toxicology and Exposure, the team used the module to create a risk assessment from the VOCs present. Their analysis identified 46 VOCs, and the average levels in the area studied were higher than those they found in Middleton, Ohio, about 520 miles away.

The levels of hydrogen cyanide—which disrupts the body’s use of oxygen and can cause death—and four other VOCs were at least 1.8-fold higher near the incidence site. Of the 46 VOCs, approximately 45 percent were classified as high hazards, and 39 percent were classified as very high hazards.

“Each of the VOC levels we detected were individually below the hazard thresholds for single exposures, but we currently do not fully understand what the hazard thresholds would be for exposure to VOC mixtures such as these,” Johnson said.

She noted that facilities such as My Way contain large amounts of harmful toxins, and a large number of different toxins, which makes prediction of the VOCs produced in fires and similar disasters difficult.

“Fires at recycling plants and other typically smaller-scale disasters are usually overlooked as contributors to pollution levels, but they also are happening more frequently across the United States,” Johnson said. “This makes research and the application of research findings a pressing public health issue.”

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JOURNAL

Journal of Exposure Science & Environmental Epidemiology

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

The application of PTR-MS and non-targeted analysis to characterize VOCs emitted from a plastic recycling facility fire

 

Bezos Earth Fund Grant creates sustainable protein research hub at NC State

NORTH CAROLINA STATE UNIVERSITY

The Bezos Center for Sustainable Protein launched today at North Carolina State University. The Bezos Earth Fund awarded NC State $30 million over five years to lead a center of excellence to create a biomanufacturing hub for dietary proteins that are environmentally friendly, healthy, tasty, and affordable. The Earth Fund has committed $100 million to establish a network of open-access research and development centers focused on sustainable protein alternatives, expanding consumer choices. 

The center will engage partners from academia and industry to research, create, and commercialize new technologies, provide training for the emerging industry workforce, and gauge consumers’ protein preferences.

“As a land-grant university in a state with significant animal agriculture, NC State is uniquely positioned to help shape the future of sustainable food production,” said Chancellor Randy Woodson. “We’re thankful for the support from the Bezos Earth Fund that will help drive economic and workforce development in this critical area of sustainable protein production in order to feed a growing world population in an economically and environmentally sustainable way. The state legislature's funding of the Food Innovation Lab in Kannapolis and new facilities in the College of Engineering have made NC State incredibly competitive for this grant.”

Protein is essential to human health, whether it comes from animal or plant sources. Without the amino acids in protein, our cells, tissues and organs can’t function. And as the global population expands, the health of both humans and the planet will increasingly depend on widespread availability of proteins that taste good and are produced in ways that reduce greenhouse gas emissions and protect nature.

“Food production is the second largest source of greenhouse gas emissions, so it’s critical we find ways to feed a growing population without degrading the planet,” said Andrew Steer, President and CEO of the Earth Fund. “Sustainable protein has tremendous potential but more research is needed to reduce the price and boost the flavor and texture to ensure nutritious, affordable products are available. It's about choice.”

The grant funding will support research on three types of sustainable proteins: plant-based products; precision fermentation to produce proteins and nutrients that can be used in food formulations; and cultivated meat grown from animal cells.

“Feeding a growing world requires producing tasty proteins that won’t further degrade nature,”  said Andy Jarvis, the Earth Fund’s Director of Future of Food. “These centers will advance open-source, sustainable protein R&D to benefit consumer choice while protecting our planet.”

“This effort is all about expanding the sustainable protein knowledge base and ecosystem,” said Rohan Shirwaiker, James T. Ryan Professor of Industrial and Systems Engineering at NC State, principal investigator on the grant, and co-director of the center. “The center’s capabilities and partnerships will add a new dimension to expand NC State’s biotechnology and advanced manufacturing expertise.”  

The center will also provide more reasons for biomanufacturing firms to locate in North Carolina, generating jobs and economic growth. The grant funding will help prepare the workforce for jobs in advanced food technology through various university and community college partnerships, while industry partnerships will support food production and processing, including small companies and start-ups.

“This is a significant opportunity for North Carolina to not only be a state with a thriving animal-sourced foods sector, but also one where it is a powerhouse in complementary proteins, building new industry and driving economic growth for the state,” said Bill Aimutis, co-principal investigator on the grant and co-director of the new center who has extensive experience working with sustainable protein producers and start-up companies. “With the center we are looking to develop solutions that will provide greater diversity of choices for consumers that are both tasty and sustainable.”

NC State will work with academic partners N.C. A&T State University, the University of North Carolina at Pembroke, Duke University, and Forsyth Tech Community College on the research, workforce development, and community engagement efforts. More than 20 industry partners will also be part of the center, which will facilitate technology transfer and student internships and mentorships.

This announcement builds on the Bezos Earth Fund’s $1 billion grant commitment to help transform food and agricultural systems to support healthy lives without degrading the planet, which also includes efforts to reduce emissions from livestock.

More information on the center and its work is available.

 

U of T researchers discover ‘trojan horse’ virus hiding in human parasite

UNIVERSITY OF TORONTO

 

IMAGE: 

UNDERGRADUATE STUDENT PURAV GUPTA AND ASSISTANT PROFESSOR ARTEM BABAIAN.

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CREDIT: UNIVERSITY OF TORONTO

An international team led by researchers at the University of Toronto has found a new RNA virus that they believe is hitching a ride with a common human parasite.

The virus, called Apocryptovirus odysseus, along with 18 others that are closely related to it, was discovered through a computational screen of human neuron data – an effort aimed at elucidating the connection between RNA viruses and neuroinflammatory disease. The virus is associated with severe inflammation in humans infected with the parasite Toxoplasma gondii, leading the team to hypothesize that it exacerbates toxoplasmosis disease.

“We discovered A. odysseus in human neurons using the open-science Serratus platform to search through more than 150,000 RNA viruses” said Purav Gupta, first author on the study, recent high school graduate and current undergraduate student at U of T’s Donnelly Centre for Cellular and Biomolecular Research. “Serratus identifies RNA viruses from public data by flagging an enzyme called RNA-dependent RNA polymerase, which facilitates replication of viral RNA. This enzyme allows the virus to reproduce itself and for the infection to spread.”

The study was published recently in the journal Virus Evolution.

The parasite T. gondii is far-reaching, infecting an estimated one-third of the global population. It can live in any non-blood cell type, including neurons, forming cysts inside cells. The parasite is transmitted to nearby cells when the infected cell ruptures.

T. gondii infections often go unnoticed because they only lead to symptoms in rare cases. Regardless, toxoplasmosis merits investigation considering how widespread it is and the potential effects it may have on pregnant women and those who are immunocompromised, Gupta said.

“We believe the virus and parasite work hand-in-hand to cause disease in the human host, where the virus hides inside the parasite, like a soldier in a trojan horse, to gain entry to the human brain,” said Gupta. “Our research marks the first time that scientists have connected toxoplasmosis to a virus.”

The newly discovered A. odysseus is found in two hypervirulent strains of the T. gondii parasite, referred to as RUB and COUGAR.

RUB has been documented in French Guinea to cause severe fever and organ failure, while COUGAR has been shown in British Columbia to be connected to ocular toxoplasmosis – the leading cause of infectious blindness. Researchers found the strains in different geographical locations at different times, demonstrating their potentially wide-ranging impacts.

Symptoms of toxoplasmosis can be aggravated by a hyperactivated human immune response. The virus-carrying parasite triggers this type of response when the immune system senses the foreign RNA of the virus.

“The group of 19 RNA viruses we found are strong biomarkers for parasitic infection,” said Artem Babaian, principal investigator on the study and assistant professor of molecular genetics at the Donnelly Centre and the Temerty Faculty of Medicine. “It’s obvious now that the A. odysseus virus could be a valuable marker of disease-causing infections, like severe toxoplasmosis, in humans or other animals. The next step is to test if this raises the possibility that treating a parasite's viruses could be an effective means of treating symptoms that arise from parasitic infections.”

Zoonotic viruses that infect other living things in our environment in order to reach us are expected to cause the majority of emerging infectious diseases in humans, Babaian noted. “This study underscores the importance of looking beyond the viruses that infect humans directly into the extended virome,” he said.

This research was supported by the Canadian Institutes of Health Research.

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JOURNAL

Virus Evolution

DOI

10.1093/ve/veae040 

ARTICLE TITLE

A parasite odyssey: An RNA virus concealed in Toxoplasma gondii

 

Clues to mysterious disappearance of North America’s large mammals 50,000 years ago found within ancient bone collagen

Dr Mariya Antonosyan, Dr Torben Rick, and Prof Nicole Boivin are co-authors of a new Frontiers in Mammal Science article in which they used new methods to identify fossil bone fragments housed at the Smithsonian’s National Museum of Natural History.

FRONTIERS

 

IMAGE: 

USNM 23792, MAMMUTHUS PRIMIGENIUS, OR WOOLLY MAMMOTH (COMPOSITE), DEPARTMENT OF PALEOBIOLOGY, SMITHSONIAN INSTITUTION. 

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CREDIT: PHOTO BY GARY MULCAHEY.

50,000 years ago, North America was ruled by megafauna. Lumbering mammoths roamed the tundra, while forests were home to towering mastodons, fierce saber-toothed tigers and enormous wolves. Bison and extraordinarily tall camels moved in herds across the continent, while giant beavers plied its lakes and ponds. Immense ground sloths weighing over 1,000 kg were found across many regions east of the Rocky Mountains.

And then, sometime at the end of the Last Ice Age, most of North America’s megafauna disappeared. How and why remains hotly contested. Some researchers believe the arrival of humans was pivotal. Maybe the animals were hunted and eaten, or maybe humans just altered their habitats or competed for vital food sources. But other researchers contend that climate change was to blame, as the Earth thawed after several thousand years of glacial temperatures, changing environments faster than megafauna could adapt. Disagreement between these two schools has been fierce and debates contentious.

Despite decades of study, this Ice Age mystery remains unsolved. We simply don’t have sufficient evidence at this point to rule out one scenario or the other – or indeed other explanations that have been proposed (eg disease, an impact event from a comet, a combination of factors). One of the reasons is that many of the bones through which we track the presence of megafauna are fragmented and difficult to identify. While some sites preserve megafaunal remains really well, conditions at others have been tough on the animal bones, wearing them down into smaller fragments that are too altered to identify. These decay processes include exposure, abrasion, breakage, and biomolecular decay.

Such problems leave us lacking critical information about where particular megafaunal species were distributed, exactly when they disappeared, and how they responded to the arrival of humans or the climatic alteration of environments in the Late Pleistocene.

Applying modern technology to old bones

Our work has set out to address this information deficit. To do so, we have turned our attention to the exceptional collections of the Smithsonian National Museum of Natural History in Washington, DC. Housing the findings of numerous archaeological excavations conducted over the past hundred years, the Museum is an extraordinary reservoir of animal bones that are deeply relevant to the question of how North America’s megafauna went extinct. Yet many of these remains are heavily fragmented and unidentifiable, meaning their ability to shed light on this question has, at least up until now, been limited.

Fortunately, recent years have seen the development of new biomolecular methods of archaeological exploration. Rather than heading out to excavate new sites, archaeologists are increasingly turning their attention to the scientific laboratory, using new techniques to probe existing material. One such novel technique is called ZooMS – short for Zooarchaeology by Mass Spectrometry. The method relies on the fact that while most of its proteins degrade quickly after an animal dies, some, like bone collagen, can preserve over long time periods. Since collagen proteins frequently differ in small, subtle ways between different taxonomic groups of animals, and even individual species, collagen sequences can provide a kind of molecular barcode to help identify bone fragments that are otherwise unidentifiable. So, collagen protein segments extracted from minute quantities of bone can be separated and analyzed on a mass spectrometer to perform the identifications of remnant bones that traditional zooarchaeologists cannot.

Selecting archaeological material for study

We decided to use this method to revisit the Smithsonian Museum’s archived material. Our study was a pilot one that asked the key question: would bones housed in the Smithsonian Museum preserve sufficient collagen for us to learn more about fragmented bone material in its storerooms? The answer was not obvious, because many of the excavations had taken place decades ago. While the material had been stored for the last decade or so in a state-of-the-art, climate-controlled facility, the early date of the excavations meant that modern standards were not necessarily applied to their handling, processing, and storage at all stages.

We examined bone material from five archaeological sites. The sites all dated to the Late Pleistocene/earliest Holocene (c. 13,000 to 10,000 calendar years before present) or earlier and were located in Colorado, in the western United States. The earliest had been excavated in 1934, the latest in 1981. Although some of the material from the sites was identifiable, much of it was highly fragmented and did not retain diagnostic features that could enable zooarchaeological identification to species, genus or even family. Some of the bone fragments looked highly unpromising – they were bleached and weathered, or edge-rounded, suggesting they had been transported by water or sediment prior to burial at the site.

Discovering excellent biomolecular preservation

What we found surprised us. Despite the old age of many of the collections, the unpromising appearance of much of the material, and the ancient origins of the bones themselves, they yielded excellent ZooMS results. In fact, a remarkable 80% of the bones sampled yielded sufficient collagen for ZooMS identifications. 73% could be identified to genus level.

The taxa we identified using ZooMS included Bison, Mammuthus (the genus to which mammoths belong), Camelidae (the camel family), and possibly Mammut (the genus to which mastodons belong). In some cases, we could only assign the specimens to broad taxonomic groups because many North American animals still lack ZooMS reference libraries. These databases, which are comparatively well developed for Eurasia but not for other regions, are essential for identifying the spectra a sample produces when we run it on a mass spectrometer.

Our findings have major implications for museum collections. The material we looked at is in every way the poor cousin of the glamorous material that goes on display in natural history museums. To look at, these highly fragmentary, small and undiagnostic animal bones are uninspiring and superficially uninformative. But like other biomolecular tools, ZooMS is revealing the rich information retained in neglected specimens that have drawn neither researcher nor visitor attention for decades.

Our results also highlight the potential of such collections for addressing ongoing debates about exactly when, where and how megafauna went extinct. By opening up for analysis the fragmented bone material that makes up much of the megafaunal record, ZooMS has the potential to help provide much new research data to address long-standing questions about megafaunal extinctions. ZooMS offers a relatively easy, rapid, and cheap way to extract new information from long-ago excavated sites.

Our research also highlights the importance of preserving archaeological collections. When researchers and institutions are strapped for funding, archaeological artefacts and bones that are not glamorous or of obvious immediate benefit may be neglected or even discarded. It is critical that museums are provided with adequate funding to care for and house archaeological remains over the long term. As our analysis shows, such old material can find new life in unexpected ways – in this case, allowing us to use tiny bone fragments to help get a little closer to solving the mystery of why some of Earth’s largest ever animals disappeared from the landscapes of ancient North America.

Preparation of a sample plate for ZooMS analysis

The preparation of a sample plate for ZooMS analysis. The tiny droplets being deposited using the pipette contain small amounts of ground up collagen that will be analyzed on a mass spectrometer. 

CREDIT

Photo by Samantha Brown

1961 excavation at Lamb Spring, showing Ed Lewis (standing on left) and Waldo Wedel, along with two fieldmen. Glenn Scott can be seen in the excavation pit alongside some mammoth bones wrapped in plaster jackets for preservation.

CREDIT

Image: USGS public domain image.

JOURNAL

Frontiers in Mammal Science

DOI

10.3389/fmamm.2024.1399358 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

A new legacy: potential of zooarchaeology by mass spectrometry in the analysis of North American megafaunal remains

ARTICLE PUBLICATION DATE

31-May-2024

 

Researchers identify a genetic cause of intellectual disability affecting tens of thousands

Novel study links genetic changes in a non-coding gene called RNU4-2 to neurodevelopmental disorders

THE MOUNT SINAI HOSPITAL / MOUNT SINAI SCHOOL OF MEDICINE

 

IMAGE: 

SCHEMATIC SHOWING THE STRUCTURES OF U4 AND U6 RNAS, AND THE INTERACTIONS BETWEEN THEM. MUTATIONS IN THE HIGHLIGHTED REGIONS OF U4 CAUSE A NEURODEVELOPMENTAL DISORDER THAT AFFECTS TENS OF THOUSANDS.

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CREDIT: LAB OF ERNEST TURRO, PHD, AT ICAHN MOUNT SINAI.

New York, NY [May 31, 2024]—Researchers at the Icahn School of Medicine at Mount Sinai and others have identified a neurodevelopmental disorder, caused by mutations in a single gene, that affects tens of thousands of people worldwide. The work, published in the May 31 online issue of Nature Medicine [DOI: 10.1038/s41591-024-03085-5], was done in collaboration with colleagues at the University of Bristol, UK; KU Leuven, Belgium; and the NIHR BioResource, currently based at the University of Cambridge, UK.

The findings will improve clinical diagnostic services for patients with neurodevelopmental disorders.

Through rigorous genetic analysis, the researchers discovered that mutations in a small non-coding gene called RNU4-2 cause a collection of developmental symptoms that had not previously been tied to a distinct genetic disorder. Non-coding genes are parts of DNA that do not produce proteins. The investigators used whole-genome sequencing data in the United Kingdom's National Genomic Research Library to compare the burden of rare genetic variants in 41,132 non-coding genes between 5,529 unrelated cases with intellectual disability and 46,401 unrelated controls.

The discovery is significant, as it represents one of the most common single-gene genetic causes of such disorders, ranking second only to Rett syndrome among patients sequenced by the United Kingdom's Genomic Medicine Service. Notably, these mutations are typically spontaneous and not inherited, providing important insights into the nature of the condition.

“We performed a large genetic association analysis to identify rare variants in non-coding genes that might be responsible for neurodevelopmental disorders,” says the study's first author Daniel Greene, PhD, Assistant Professor of Genetics and Genomics Sciences at Icahn Mount Sinai and a Visitor at the University of Cambridge. “Nowadays, finding a single gene that harbors genetic variants responsible for tens of thousands of patients with a rare disease is exceptionally unusual. Our discovery eluded researchers for years due to various sequencing and analytical challenges.”

More than 99 percent of genes known to harbor mutations that cause neurodevelopmental disorders encode proteins. The researchers hypothesized that non-coding genes, which don't produce proteins, could also host mutations leading to intellectual disability. Neurodevelopmental disorders, which often appear before grade school, involve developmental deficits affecting personal, social, academic, or occupational functioning. Intellectual disability specifically includes significant limitations in intellectual functioning (e.g., learning, reasoning, problem-solving) and adaptive behavior (e.g., social and practical skills).

“The genetic changes we found affect a very short gene, only 141 units long, but this gene plays a crucial role in a basic biological function of cells, called gene splicing, which is present in all animals, plants and fungi," says senior study author Ernest Turro, PhD, Associate Professor of Genetics and Genomic Sciences at Icahn Mount Sinai and a Visitor at the University of Cambridge. “Most people with a neurodevelopmental disorder do not receive a molecular diagnosis following genetic testing. Thanks to this study, tens of thousands of families will now be able to obtain a molecular diagnosis for their affected family members, bringing many diagnostic odysseys to a close.”

Next, the researchers plan to explore the molecular mechanisms underlying this syndrome experimentally. This deeper understanding aims to provide biological insights that could one day lead to targeted interventions.

"What I found remarkable is how such a common cause of a neurodevelopmental disorder has been missed in the field because we've been focusing on coding genes,” says Heather Mefford, MD, PhD, of the Center for Pediatric Neurological Disease Research at St. Jude Children’s Research Hospital who was not involved with the research. “This study's discovery of mutations in non-coding genes, especially RNU4-2, highlights a significant and previously overlooked cause. It underscores the need to look beyond coding regions, which could reveal many other genetic causes, opening new diagnostic possibilities and research opportunities."

The paper is titled “Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders.”

The remaining authors of the paper are Chantal Thys (KU Leuven, Belgium); Ian R. Berry, MD (University of Bristol, UK); Joanna Jarvis, MD (Birmingham Womens’ Hospital, UK); Els Ortibus, MD, PhD (KU Leuven, Belgium); Andrew D. Mumford, MD (University of Bristol, UK); and Kathleen Freson, PhD (KU Leuven, Belgium).

The work was supported, in part, by NIH awards R01HL161365 and R03HD111492. See the paper for further details on funding.

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About the Icahn School of Medicine at Mount Sinai

The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight- member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population.  

Ranked 13th nationwide in National Institutes of Health (NIH) funding and among the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators, and clinicians work within and across 44 academic departments and 36 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, as well as gastrointestinal and liver diseases. 

Icahn Mount Sinai offers highly competitive MD, PhD, and Master’s degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,000 clinical residents and fellows training throughout the Health System. In addition, more than 550 postdoctoral research fellows are in training within the Health System. 

A culture of innovation and discovery permeates every Icahn Mount Sinai program. Mount Sinai’s technology transfer office, one of the largest in the country, partners with faculty and trainees to pursue optimal commercialization of intellectual property to ensure that Mount Sinai discoveries and innovations translate into healthcare products and services that benefit the public.

Icahn Mount Sinai’s commitment to breakthrough science and clinical care is enhanced by academic affiliations that supplement and complement the School’s programs.

Through the Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai. Additionally, MSIP develops research partnerships with industry leaders such as Merck & Co., AstraZeneca, Novo Nordisk, and others.

The Icahn School of Medicine at Mount Sinai is located in New York City on the border between the Upper East Side and East Harlem, and classroom teaching takes place on a campus facing Central Park. Icahn Mount Sinai’s location offers many opportunities to interact with and care for diverse communities. Learning extends well beyond the borders of our physical campus, to the eight hospitals of the Mount Sinai Health System, our academic affiliates, and globally.

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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Beth Israel; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.

 

 

 

 

 

 

 

 

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JOURNAL

Nature Medicine

DOI

10.1038/s41591-024-03085-5 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders

ARTICLE PUBLICATION DATE

31-May-2024

 

Nearly one-third of US adults know someone who’s died of drug overdose

Survey also finds ‘overdose loss’ bolsters recognition of addiction as an important policy issue that spans party lines

JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH

Losing a loved one to drug overdose has been a common experience for many Americans in recent years, crossing political and socioeconomic divides and boosting the perceived importance of the overdose crisis as a policy issue, according to a new survey led by researchers at the Johns Hopkins Bloomberg School of Public Health.

A nationally representative survey of more than 2,300 Americans, fielded in spring 2023, suggests that 32 percent of the U.S. adult population, or an estimated 82.7 million individuals, has lost someone they know to a fatal drug overdose. For nearly one-fifth of survey respondents—18.9 percent, representing an estimated 48.9 million adults—the person they knew who died of overdose was a family member or close friend.

The rates of reported loss due to overdose did not differ significantly by political party affiliation, but those who experienced overdose loss were more likely to view addiction as an extremely or very important policy issue.

The study will be published online May 31 in JAMA Health Forum.

“The drug overdose crisis is a national tragedy,” says Alene Kennedy-Hendricks, PhD, assistant professor in the Department of Health Policy and Management at the Bloomberg School, who led the analysis. “Although large numbers of U.S. adults are bereaved due to overdose, they may not be as visible as other groups who have lost loved ones to less stigmatized health issues. Movements to build support for policy change to overcome the devastating toll of the overdose crisis should consider the role of this community.”

Over one million Americans have died from drug overdoses since the late 1990s, including more than 100,000 per year in the last few years, according to the Centers for Disease Control and Prevention. Last year, overdose deaths declined slightly for the first time in five years, decreasing three percent from 2022, according to preliminary data from the CDC’s National Center for Health Statistics. At about 108,000 estimated deaths, the CDC 2023 preliminary numbers remain near historic highs. 

The overdose crisis has evolved over several phases, beginning with prescription opioids such as oxycodone playing a key role, followed by heroin and, more recently, powerful synthetic opioids like illicitly manufactured fentanyl and polysubstance use. Opioids can suppress breathing as a side effect, and the unpredictability of the illicit drug supply and the potency of fentanyl have dramatically increased the risk of overdose.

While the survey questions did not specifically identify opioids, the majority of overdose deaths over the last two decades have been opioid-related.

The overdose crisis has not only impacted its direct victims but also their relatives, friends, and acquaintances. Kennedy-Hendricks and her colleagues at the Bloomberg School’s Center for Mental Health and Addiction Policy set up the study to help illuminate this wider impact, which otherwise has been little studied.

The paper was co-written with colleagues from Boston University School of Public Health, the University of Minnesota, and the de Beaumont Foundation. The study’s senior author is Sandro Galea, MD, DrPH, MPH, dean of Boston University School of Public Health. 

The survey is part of the CLIMB (COVID-19 and Life Stressors Impact on Mental Health and Well-being) study. Led by Catherine Ettman, PhD, an assistant professor in the Bloomberg School’s Department of Health Policy and Management, the CLIMB study has surveyed a nationally representative sample of adult Americans annually since 2020. For this overdose loss study, questions to participants from March 28 to April 17, 2023—CLIMB Wave 4—included “Do you personally know anyone who has died from a drug overdose?” A total of 2,326 participants responded to the question. Participants answering “yes” were then asked “Who do you know that has died from a drug overdose?”  

Overdose losses were reported across all income groups. Forty percent of lower-income respondents (defined as annual household incomes less than $30,000) reported overdose loss. Over one-quarter—26 percent—of respondents in the $100,000 and higher annual household income category reported an overdose loss.

The rate of reported overdose loss was not significantly different across self-described Republicans, Democrats, and Independents, adding to the picture of a far-reaching phenomenon.

The data suggested a high level of endorsement across all groups—greater than 60 percent, even among those reporting no overdose loss—that addiction is an extremely or very important policy issue. Respondents who reported overdose loss had 37 percent greater odds of viewing addiction as a very or extremely important policy priority. 

“This study contributes new evidence that the addiction crisis and the losses that come with it are common across Americans, but the burden is greater among those who are more economically precarious,” says Ettman. “Addressing addiction can be a unifying theme in increasingly divided times.”

The researchers plan to follow up with further studies in future CLIMB survey waves, looking at associations between overdose loss and other social variables such as trust in institutions.

“The Scale of Personal Loss Incurred by the Drug Overdose Crisis in the U.S.” was co-authored by Alene Kennedy-Hendricks, Catherine Ettman, Sarah Gollust, Sachini Bandara, Salma Abdalla, Brian Castrucci, and Sandro Galea.

CLIMB Study Wave 4 was funded by a grant from the de Beaumont Foundation.

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BU study finds policy makers’ use of in-hospital mortality as a sepsis quality metric may unfairly penalize safety-net hospitals

BOSTON UNIVERSITY SCHOOL OF MEDICINE

(Boston)—Sepsis is a leading cause of death and disability and a key target of state and federal quality measures for hospitals. In-hospital mortality of patients with sepsis is frequently measured for benchmarking, both by researchers and policymakers. For example, in New York, sepsis regulations mandate reporting of risk-adjusted in-hospital mortality, and hospitals with lower or higher than expected in-hospital mortality rates are publicly identified as high or low performers. Safety net hospitals (which face unique challenges, including fewer resources to care for a disproportionately high share of underinsured and high-risk patients) have been reported in prior studies to have higher risk-adjusted in-hospital mortality among patients with sepsis than non-safety-net hospitals.

However, among critically ill patients, in-hospital mortality may not adequately reflect short-term mortality fairly across all hospitals. In-hospital mortality is influenced by other variables, including hospital transfer practices, which shift the attribution of short-term death from the hospital to other sites. Safety-net hospitals may have different access or ability to transfer patients compared to non-safety-net hospitals.

In a new study, researchers at Boston University Chobanian & Avedisian School of Medicine found that safety net hospitals do have higher in-hospital mortality than non-safety net hospitals, but their 30-day mortality – an unbiased measure of short-term mortality – is actually not different.

 

“While the differences in mortality rates are numerically small, the difference in outcome metrics is enough to significantly affect hospital rankings. Current or future state and federal quality measures that use in-hospital mortality as a quality metric may unfairly penalize safety-net hospitals,” explained corresponding author Anica Law, MD, MS, assistant professor of medicine at the school.

The researchers performed a retrospective analysis of patients with sepsis who were aged 66 and older and were admitted to an intensive care unit between January 1, 2011, through December 31, 2019, at both safety and non-safety net hospitals.

“Although in-hospital mortality is often selected as an outcome measure because of its availability in claims databases and hospital medical records without need for post-hospitalization follow-up, the 30-day measure is important to accurately understand true short-term mortality rates,” said Law, who also is a pulmonologist and critical care physician at Boston Medical Center.

According to the researchers, the difference appears to be due partly to the fact that non-safety net hospitals discharge more patients to hospice, which shifts attribution of short-term mortality away from the index hospitalization. “When post-hospitalization data is incorporated, as is done in 30-day mortality analysis, you get a more accurate picture of who is actually dying in the short-term, and see that there no longer a difference between safety and non-safety net hospitals.” The Centers for Medicare and Medicaid Services (CMS) has already legislated a process measure that assesses whether hospitals are performing key sepsis care steps efficiently, including initiating antibiotics. CMS is currently considering rolling out a national sepsis outcome measure; it is not yet known if CMS will be measuring in-hospital mortality or 30-day mortality.

These findings appear online in JAMA Network Open.    

Funding for this study was provided by the National Institute of Health (NIH)/National Heart, Lung, and Blood Institute (NHLBI) K23HL153482, National Center for Advancing Translational Sciences (NCATS) 1KL2TR001411, the Doris Duke Charitable Foundation, the Boston University Evans Junior Faculty Merit Award, and the Boston University Chobanian & Avedisian School of Medicine Department of Medicine Career Investment Award.

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JOURNAL

JAMA Network Open

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

In-Hospital vs 30-Day Sepsis Mortality at US Safety-Net and Non–Safety-Net Hospitals

ARTICLE PUBLICATION DATE

31-May-2024

 

Stem cells shed new light on how the human embryo forms

UNIVERSITY OF EXETER

A new study using stem cell-based models has shed new light on how the human embryo begins to develop, which could one day benefit the development of fertility treatment.

The study led by at the University of Exeter Living Systems Institute has revealed how early embryo cells decide between contributing to the foetus or to the supporting yolk sac.

Understanding this decision is important because the yolk sac is essential for later development in the womb. Producing the right number of yolk sac forming cells may be critical for infertility treatment using in vitro fertilised (IVF) embryos.

Only limited research can be performed directly on human embryos. The research team which included the University of Edinburgh, therefore used naïve stem cells that are able to make all the cell types and structures of the early embryo. They designed stem cell models to study formation of yolk sac founders, called hypoblast.

The key discovery, published in Cell Stem Cell, is pinpointing a critical signal that acts during a short window of time, less than one day, to trigger cells to become hypoblast. The signal is a protein called fibroblast growth factor that is made within the embryo. Previous studies had missed the importance of this signal in human embryos. The new findings show that the initial processes that form an embryo and its supporting tissues are similar for humans and other mammals.

Lead author Dr Ge Guo, of the University of Exeter’s Living System Institute, said: “Our findings provide insights into how the correct proportions of different cell types form in the early human embryo. We hope our research will benefit infertility treatment in future.”

Professor Austin Smith, the Director of the University of Exeter’s Living Systems Institute, said: “This study shows the power of stem cell-based models for revealing how the human embryo begins to develop. This marks a significant milestone in stem cell research and embryo models, providing a framework for future research into the early development of the human embryo.

The paper is entitled ‘Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification’ and is published in Cell Stem Cell. The work is a collaboration with Professor Jennifer Nichols at the University of Edinburgh.

ENDS 

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JOURNAL

Cell Stem Cell

DOI

10.1016/j.stem.2024.05.003 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Naive pluripotent stem cell-based models capture FGF-dependent human hypoblast lineage specification’

ARTICLE PUBLICATION DATE

31-May-2024

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