Friday, June 02, 2023

Lab-grown mini lungs could accelerate the study of respiratory diseases

Peer-Reviewed Publication

ROCKEFELLER UNIVERSITY

Human mini-lungs 

IMAGE: SARS-COV-2 (MAGENTA) INFECTS ALVEOLAR AND AIRWAY TISSUES (BLUE) OF HUMAN MINI-LUNGS DERIVED IN VITRO FROM HUMAN PLURIPOTENT STEM CELLS. view more 

CREDIT: LABORATORY OF SYNTHETIC BIOLOGY AT THE ROCKEFELLER UNIVERSITY

When we’re driving to a new destination, we often turn down the stereo as we follow the directions. What had been music suddenly sounds like noise, and it interferes with our focus.

Our understanding of how infectious diseases like COVID affect human lungs has been similarly confounded by noise. Data from patient lung tissues greatly varies from person to person, obscuring the basic mechanisms of how, exactly, SARS-Co-V2 first infects lung cells. It’s also an after-the-fact analysis—as if we’re trying to map the route the virus took three states back.

Turning down the noise of variability by studying genetically identical tissues from the first moment of infection could light up the route the pathogen takes. Which cells are infected, and when? What is the level of infection, and how does it differ depending on cell type? How does it change in different conditions?

And what if it were possible to track thousands of these infections at once? It might revolutionize our understanding of both infections and the drug treatments used to combat them.

That’s the hope for new advanced tech capable of growing mini organs on microchips. The labs of Rockefeller’s Ali Brivanlou and Charles M. Rice collaborated to refine a cell culture technology platform that grows genetically identical lung buds—the embryonic structures that give rise to our breathing organs—from human embryonic stem cells (hESCs). Their findings were recently published in Stem Cell Reports.

When placed on an array of microchips and carefully dosed with a custom cocktail of signaling molecules, the hESCs rapidly organize themselves into “micro lungs” that have full tissue complexity. These buds can be cultured by the thousands, allowing for an unprecedented high-throughput analysis of lung tissue infection without all the noisy variables.

The result is unlimited, fast, and scalable access to lung tissue that has the key hallmarks of human lung development and can be used to track lung infections and identify candidate therapeutics.

“These lungs are basically clones,” says Ali Brivanlou. “They have the exact same DNA signature. That way we don’t have to worry about one patient responding differently from another. Quantification allows us to keep the genetic information constant and measure the key variable—the virus.”

Building a better mini lung

Embryonic stem cells are the Ur-cells of the human body. They can infinitely divide to create more stem cells or to differentiate into any other tissue. Brivanlou’s Laboratory of Synthetic Biology has long explored their potential.

Brivanlou joined forces with Rockefeller colleague Charles M. Rice during the COVID pandemic: his lab had the microchip technology to grow lung buds, and Rice’s lab had the necessary biosafety clearance required to infect them with SARS-Co-V2 and study the outcome.

In 2021, first authors Edwin Rosado-Olivieri, a stem cell biologist in Brivanlou’s lab, and Brandon Razooky, then a postdoc in Rice’s Laboratory of Virology and Infectious Disease, began coaxing the cells to organize into more specialized forms. Stem cells don’t just organize on their own. They need a confined space—such as a microchip well—and stimuli to spark change. The stimuli come from four main signaling pathways that induce stem cells to differentiate into specific cell types.

After about two weeks, the group’s lung cells had formed identical buds whose molecular profiles closely matched those seen in the earliest stages of fetal lung development—including the formation of airways and alveoli, structures known to be damaged in many people with severe COVID.

Identifying a key culprit

Since then, they’ve used the platform to understand how SARS-Co-V2 infects different lung cells.

Alveoli are tiny sacs at the end of the lung branches that manage the gas exchange performed with every breath: oxygen in, carbon dioxide out. By studying cloned alveoli cells en masse, the researchers discovered that alveoli were more susceptible to SARS-Co-V-2 infection than airway cells, which are the guardians of the organ—the first defense against all inhaled threats. If the virus got past them, the alveoli were sitting ducks.

Another view of virus particles (blue) infecting alveolar and airway tissues (red).

They also hit upon a winning combination of signaling proteins for creating the most robust batches of lung buds—a mix of keratinocyte growth factor (KGF) and bone morphogenetic protein 4 (BMP4). Both contribute to cell differentiation and growth.

Interestingly, the BMP pathway has a downside. When they compared infected lung buds to postmortem tissue of COVID patients, they found that the BMP signaling pathway was induced in both and rendered the tissues more vulnerable to infection. Blocking the BMP pathway made the cells less vulnerable.

Beyond COVID

The researchers note that the platform can also be used to investigate the mechanisms of influenza, RSV, pulmonary diseases, and lung cancer, among other diseases. Moreover, it can be used to screen for new drugs to treat them.

And lungs are far from the only organ of interest. “The broader focus of our work is understanding cellular development to make synthetic organs and tissues that we can use to model diseases and find therapeutic mechanisms,” says Rosado-Olivieri. The liver, kidney, and pancreas are all likely next targets.

“The platform will also allow us to respond to the next pandemic with much more speed and precision,” Brivanlou adds. “We can quickly capitalize on this platform to make a virus visible and develop therapies much faster than we did for COVID. It can be used to screen for drugs, compounds, vaccines, monoclonal antibodies, and more directly in human tissue. This technology is ready to confront all kinds of threats that may hit us in the future.”

Tweets showed increasing loneliness among emergency medicine doctors during COVID-19

Peer-Reviewed Publication

UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE

Expressions of loneliness and depression from emergency medicine doctors increased consistently on social media as the COVID-19 pandemic wore on, according to a new JAMA Network Open study by researchers at the Perelman School of Medicine and the School of Engineering and Applied Sciences at the University of Pennsylvania. Using artificial intelligence to process Twitter posts from nearly 500 emergency medicine (EM) physicians, the study team found that mentions of these feelings — along with anxiety and anger — went from relatively rare before the pandemic to common after COVID-19 became widespread in the United States in March 2020.

“The consistent and real rise of loneliness among emergency medicine physicians was shocking, and I’d hypothesize that this may have been true across medicine at large,” said co-lead author Anish Agarwal, MD, the chief wellness officer for Emergency Medicine and deputy director for the Penn Medicine Center for Digital Health. “The surgeon general recently highlighted an epidemic of loneliness in America, and this seems to really indicate that it doesn’t spare health care workers. If anything, this issue has been potentially worse within medicine and, in a field so affected by burnout and emotional strain, we believe this gives us another lens to explore these problems in the future.”

Amid the worst of COVID-19, many physicians, particularly those on the front lines in emergency departments, opened up on social media about what they were seeing every day. At a time when there was some mystery — and disinformation — about a disease circling the globe, physicians became more prominent online. This influx of attention and posts, therefore, provided a trove of data that could be studied to better understand shifts going on in the profession as a whole during the  crisis.

Agarwal, co-lead author Sharath Guntuku, PhD, an assistant professor of Computer and Information Science and a Senior Fellow in the Leonard Davis Institute of Health Economics at Penn, and their fellow researchers used machine learning techniques to assess themes and specific language relating to emotions in the public tweets of emergency medicine physicians, stretching from 2018 to 2022. The Twitter accounts they pulled data from belonged to doctors working in counties with the highest COVID-19 case loads, including New York, Maricopa, Ariz., and Los Angeles. Information from tweets were broken up into pre- and post-pandemic segments, with March 2020 as the dividing line.

Agarwal and Guntuku’s study showed that negative emotions and themes were expressed much more often amid the pandemic, and positive themes took a significant dive. The expressions of loneliness in physician tweets increased by as much as 17% during the two years of COVID-19 pandemic they analyzed, compared to the two years prior. Similar increases were observed with expressions of anger and anxiety, though they reverted roughly toward pre-pandemic levels eventually. Loneliness and depression appeared to have remained elevated at the end of the study’s observed time period, though they weren’t quite at their peaks.

The study also provided insights into how much COVID-19 dominated emergency medicine clinicians’ thoughts after March 2020. The top five themes in the pre-pandemic period were “free open-access medical education in emergency medicine,” “residency education,” “gun violence,” “quality improvement in health care,” and “resident professional societies.” However, since the pandemic started, the top themes identified were “healthy behaviors,” “pandemic response,” and “vaccines and vaccination.” Even those that may not be directly related to health care had clear ties to the pandemic, as “unstable housing and homelessness” and “emotional support for others,” were top concerns during the height of COVID-19’s spread.

Seeing these trends and building a system in which the general mood of an entire industry can be taken could be key to fighting burnout that is hitting every level of health systems across the nation.

“The ability to measure these changes, using language on social media, provides an opportunity to address the underlying challenges and potentially intervene to improve the well-being of our healthcare workforce,” Guntuku said. 

Agarwal emphasized that what they found shows a need to “invest in social connectedness” of health care workers of all stripes.

“We likely need to reinforce mentorship, connection, and career growth across the board,” Agarwal said. “It’s a challenging field — no one denies that — and, to get through, it takes a village. Let’s rebuild and sustain that village.”

This study was partially supported by the National Institutes of Health (R01MD018340, R01MH127686) and the National Heart, Lung and Blood Institute (K24 HL157621).

NASA grant funds aeroacoustic research to develop quieter vertical lift air vehicles


As noise levels in urban spaces swell, a multi-university partnership seeks to turn down the volume on urban air mobility vehicles

Grant and Award Announcement

VIRGINIA TECH

A researchers prepares for particle image velocimetry measurements 

IMAGE: A RESEARCHERS PREPARES FOR PARTICLE IMAGE VELOCIMETRY MEASUREMENTS OF UNSTEADY INFLOW INTO A ROTOR INSIDE THE TEST SECTION OF VIRGINIA TECH’S STABILITY WIND TUNNEL. view more 

CREDIT: PHOTO COURTESY OF NATHAN ALEXANDER FOR VIRGINIA TECH.

Drone delivery is rapidly taking off in major cities, with rotor-powered rideshares not far behind. The convenience promised by electric vertical take-off and landing vehicles generates a substantial buzz – not just from excitement but from all the noise generated by rotors filling the sky. 

To address key challenges facing the future of air transport, NASA has awarded $5.7 million to a multi-university partnership as part of the agency’s University Leadership Initiative.

The project, led by Boston University over the next three years, will bring together researchers and engineers from Virginia Tech, Embry-Riddle University, Tuskegee University, and industry partner Joby Aviation to focus on developing quieter vertical lift air vehicles.

Advanced or urban air mobility concept vehicles are typically electric vertical take-off and landing, commonly called eVTOL, vehicles with four or more rotors. The grant will support research into the technical and environmental challenges of flying in urban environments.

Added convenience, added noise

As populations in urban areas continue to grow, increased traffic and industrial activity is causing cities to become louder and louder. Factoring in new modes of transportation, such as vertical lift air vehicles, will contribute to already existing noise pollution. 

The research will develop methods to better predict low noise operations of such vehicles within the urban canyon. The research team will explore how much the ingestion of large-scale disturbances during flight, such as gusts of winds, will affect rotor noise.  

“This is a complicated problem,” said W. Nathan Alexander, assistant professor in the Kevin T. Crofton Department of Aerospace and Ocean Engineering. “While a helicopter has one main rotor, these vehicles have multiple rotors. This provides additional degrees of freedom to control sound through individual rotor RPM and tilt, but it also makes the problem more complex. The goal is to determine the optimal configuration for safe operations in unsteady environments that also produce low noise.” 

Both computational and experimental methods will be used to satisfy the research objectives.

Virginia Tech will take point on the experimental studies and has been awarded $1.3 million from the total NASA grant. Alexander, an expert in fluid dynamics, flow-structure interaction, and flow generated noise, will team with Nanyaporn Intaratep, research assistant professor, to plan and execute testing in the Stability Wind Tunnel. 

The Stability Wind Tunnel is one of the leading university-owned research facilities of its kind specializing in aerodynamic and aeroacoustic testing. In addition to low background noise, the facility boasts state-of-the-art instrumentation and unique capabilities for measuring aeroacoustic flow, such as its 251-channel microphone array and stereoscopic particle image velocimetry  systems. 

Working with Joby Aviation, Alexander and Intaratep will design and conduct experiments to assess the aerodynamic and acoustic performances of multirotor configurations. 

The team’s experiments will focus on the rotors themselves – studying their interaction in gusty environments, and measuring the RPM, thrust, torque, and noise from a variety of angles, as well as the flow field in and around those rotors. 

The data captured will help validate computational models from university partners to predict the steady state noise as well as a vehicle’s response to disturbances in an urban setting. 

Throughout the experimentation phase, Alexander and Intaratep will also develop a virtual lab to increase the research’s educational impact. “Most institutions do not have a facility like the Stability Wind Tunnel,” Alexander said. “By using what we learned over the COVID-19 pandemic in delivering a meaningful, online lab experience, we will be able to offer students at our partner universities the ability to participate in real flow and noise data acquisition and processing.” 

The methods and data derived from this study will be open-sourced, aiding in the industry advancement of vertical lift air vehicles. The research will also provide graduate and undergraduate students hands-on research experience related to the urban air mobility industry.

Honey bee colony aggression linked to gene regulatory networks


Peer-Reviewed Publication

CARL R. WOESE INSTITUTE FOR GENOMIC BIOLOGY, UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN

Honey bees 

IMAGE: HONEY BEE COLONY view more 

CREDIT: UIUC



Collective behaviors are present across many different animal groups: schools of fish swimming in a swirling pattern together, large flocks of birds migrating through the night, groups of bees coordinating their behavior to defend their hive. These behaviors are commonly seen in social insects where as many as thousands of individuals work together, often with distinct roles. In honey bees, the role a bee plays in the colony changes as they age. Younger bees perform duties inside the hive, such as nursing and wax building, while older bees transition to roles outside of the hive, either foraging for food (foragers) or defending the colony (soldiers).

What determines whether older bees become foragers or soldiers is unknown, but a new study published in Nature Ecology and Evolution explores the genetic mechanisms underlying the collective behavior of colony defense, and how these mechanisms relate to the colony’s overall aggression.

“Honey bees do not have a size-based division of labor, like you might see in termites or ants,” said Ian Traniello, former graduate student at University of Illinois Urbana-Champaign, now an associate research scholar at Princeton University and first author on the study. “If you ask anyone off the street to guess which ant is a soldier versus a forager, they probably will guess it right 100% of the time, because the soldiers are huge. Honey bees instead have an age-based division of labor, where older bees tend to be foragers or soldiers, both of which are dangerous and potentially lethal roles.”

A genome-wide association study conducted previously on a sub-species of honey bee in Puerto Rico that had evolved to be less aggressive in recent years, revealed strong associations between variation in the sequence of some genes and the level of overall colony aggression. Researchers called these “colony aggression genes.”

In the current study, researchers compared the expression and regulation of genes in the brains of soldiers and foragers, and across colonies that varied in aggressiveness. Researchers measured colony aggressiveness by counting the number of stings on suede patches placed outside the hives after a disturbance. They identified soldiers as the bees that attacked the patches and foragers as the bees that returned to the hive with pollen. The researchers then used single-cell transcriptomics and gene regulatory network analysis to compare the brains of forager and soldier bees, from low and high aggression colonies.

The researchers found that, although there were thousands of genes in the brain that differed in their expression between soldiers and foragers, none of them were part of the colony aggression gene list. However, when they created models of brain gene regulatory networks, which control when and where specific genes are expressed, the researchers found that the structure of these networks differed between soldiers and foragers—and the differences were bigger when the soldiers and foragers came from a more aggressive colony.

“What we think is happening is that the regulation of genes associated with collective behavior affects the mechanisms that underlie division of labor,” Traniello explained. “So, colonies can become more or less aggressive by influencing the aggression level of the individuals within that colony. Basically, a forager may be more or less likely to transition to a soldier-like state if the environment calls for it.”

The findings highlight the importance of gene regulation to our understanding of the relationship between genes and behavior.

“While a few studies have found potential heritable differences between soldiers and foragers, this study demonstrates that older honey bees may have the potential to take on either role,” said Gene Robinson (GNDP), IGB Director and author on the paper. “In colonies that are more aggressive, likely due to increased danger in the environment, older bees may just be more predisposed to become soldiers to help defend the colony.”

Plans for future directions include developing functional tests to explore the role of the gene networks identified in the study, and to identify spatially where they are being expressed in the brain. Traniello says that he looks forward to exploring these new questions.

“We have extraordinary technologies to probe genes and behavior at an unprecedented scale, both with single-cell and, now, spatial transcriptomics,” Traniello said. “These give us new means for understanding old questions, like the relationship from individual to collective, or the relationship between genotype to phenotype. It’s exciting to be able to take these tools and apply them in naturalistic contexts, and I hope this work inspires others to do the same.”

The project was funded by the Illinois Sociogenomics Initiative, and can be found at https://www.nature.com/articles/s41559-023-02090-0.

Forest birds with short, round wings more sensitive to habitat fragmentation, OSU study shows


Peer-Reviewed Publication

OREGON STATE UNIVERSITY

black-throated blue warbler, photo by Matt Betts, OSU 

IMAGE: BLACK-THROATED BLUE WARBLER, PHOTO BY MATT BETTS, OSU view more 

CREDIT: BLACK-THROATED BLUE WARBLER, PHOTO BY MATT BETTS, OSU

CORVALLIS, Ore. – Tropical forest birds, which tend to have wings that are short and round relative to their body length and shape, are more sensitive to habitat fragmentation than the long-, slender-winged species common in temperate forests, according to an international collaboration that included scientists from Oregon State University.

OSU’s Matt Betts and Christopher Wolf teamed with 14 other authors to analyze the wings of more than 1,000 species worldwide in a study led by Thomas Weeks of Imperial College London and published in Nature Ecology and Evolution.

The research builds on a 2019 study that was led by Betts and Wolf and published in Science. That paper had shown that the nearer a forest species lives to the equator, where animals evolved in environments that weren’t subject to large-scale habitat-altering events like fires and storms, the less well equipped the species is to adapt to current human-caused forest fragmentation.

The wing study provides solid evidence for the idea that forest birds in the lower latitudes – the bare-faced ibis, the blue and gold macaw, the green honeycreeper, the Malaysian rail babbler and many other colorful, and colorfully named, species – aren’t good at relocating when their habitat gets broken up because they weren’t required to evolve in ways that would make it easy to get to new areas, Betts said.

“The new paper shows a strong latitudinal gradient in birds’ ability to disperse – i.e., move around to find a new place to live,” said Betts, a professor of landscape ecology in the OSU College of Forestry. “Birds toward the poles tend to be better movers, with longer, narrower wings that are better suited to long-distance flight.”

Previously, the reason behind tropical birds’ comparative lack of dispersal skills had not been well understood, and there had also been some question as to whether a forest species’ ability to move around was all that important in terms of dealing with habitat fragmentation, Wolf said.

“It had been argued that species that don’t move much maybe tend to stay put just because they don’t care about losing pieces of their habitat or seeing it fragmented,” said Wolf, a postdoctoral researcher in the College of Forestry. “But we used a massive dataset that encompassed more than 1,000 birds globally to test whether birds with shorter, stubbier wings are more likely to be fragmentation sensitive, and whether this alone explains the latitudinal gradient we observed. In the end, there was strong support for the idea that birds that are good dispersers are less fragmentation sensitive.”

Examples of temperate forest birds more built for dispersal include woodpeckers, robins, jays, cardinals, owls, turkeys, hawks and eagles.

The Natural Environment Research Council, the UKRI Global Challenges Research Fund and the Natural Environment Research Council supported this research.

Also contributing to the study were scientists from Newcastle University; the University of Toulouse; Lancaster University; the Foundation for Ecodevelopment and Conservation; the Global Protect Oceans, Lands and Waters Program; the Nature Conservancy; the Swiss Ornithological Institute; Yale University; the University of Pretoria; the Centre for Conservation of Atlantic Forest Birds; the University of Queensland; and California State University, Los Angeles.

MU textiles professor earns grant as part of USDA’s Higher Education Challenge

The new grant will be used to elevate students’ digital data literacy skills and help them meet the demands of a changing textile industry

Grant and Award Announcement

UNIVERSITY OF MISSOURI-COLUMBIA



Atosha Jisabo, a textiles and apparel management (TAM) student, presents a data analytics project at TAM’s open house event. 

IMAGE: ATOSHA JISABO, A TEXTILES AND APPAREL MANAGEMENT (TAM) STUDENT, PRESENTS A DATA ANALYTICS PROJECT AT TAM’S OPEN HOUSE EVENT. view more 

CREDIT: UNIVERSITY OF MISSOURI STAFF




When you think about big data and fashion, it seems unlikely that the two might be stitched together. However, the modern fashion industry depends on data analytics throughout the supply chain to serve customers in ways that champion innovation, including expanding designers’ creativity, calculating the environmental impact of making a product and keeping brands up to date on changes in the market.

In an inventive project funded by a Department of Agriculture (USDA) grant of $149,000 awarded to Li Zhao, a professor of textiles and apparel management in the University of Missouri’s College of Arts and Science, students will learn the tricks of the trade, becoming fluent in the language of digital data and giving them the best chance at success in a rapidly modernizing industry.

“We’re truly delighted to receive this grant as it marks a significant achievement for our project team,” Zhao said. “We appreciate the opportunity to have a positive impact on students’ education, career readiness and the broader Fiber, Textile, and Apparel and Food, Agriculture, Natural Resources, and Human (FANH) fields.”

Specifically, Zhao and her team will develop educational packets, teaching modules and datasets to enhance students’ digital data literacy skills at all levels. Understanding data is central for graduates entering the fashion industry as it provides a foundation for forecasting demand, measuring store performance and grappling with a changing market.

This project’s two main goals include:

  • Better preparing students for careers that depend increasingly on an understanding of data analytics to meet industry demands.  
  • Providing educators with much-needed datasets and educational resources to broaden the literature in this field while concentrating teaching efforts to provide a foundation based on the skills students will need to be successful in a changing field.

This project will be implemented through two primary classes: a data analytics class on understanding clothing/textile consumers and a course focused on digital merchandising.

“Overall, this grant will benefit both students and educators while addressing the current skills gap between academia and the industry,” Zhao said. “In particular, considering the discussions around data analytics and generative AI, which are also impacting the textile and apparel industry, this grant will create opportunities for students to explore new career paths in related fields.”

As advances in generative learning and AI continue to influence the way teaching functions, this grant will equip students with digital data literacy knowledge and cultivate an open-minded approach to what it means to work in an increasingly digital creative industry.

This grant is part of the Higher Education Challenge, an investment funded by the National Institute of Food and Agriculture (NIFA) intended to strengthen universities’ infrastructure, curriculum and ability to recruit top-quality faculty and students. Co-principal investigators include Jung Ha-Brookshire, Caroline Kopot and Michael Williams at MU.


Missouri farm income projected to decline in 2023

State-level report identifies key changes in projected net farm income.

Reports and Proceedings

UNIVERSITY OF MISSOURI-COLUMBIA

Missouri’s net farm income is predicted to fall in 2023 following a record-setting 2022, according to the spring 2023 Missouri Farm Income Outlook report.

The report, released by the Rural and Farm Finance Policy Analysis Center (RaFF) at the University of Missouri, provides comprehensive insights that can equip industry stakeholders and policymakers with information to understand the state-level impacts of economic factors, weather and policy initiatives on the agriculture industry. One factor that could explain this projected drop in farm income is the state’s livestock receipts, which were impacted by the country-wide drought that reduced cattle inventories and supported Missouri marketings, which is the physical sale of live animals, said RaFF interim director Scott Brown.

“Our report projects that Missouri net farm income is tapering off from a record high in 2022,” Brown said. “Production expenses remain stubbornly high while cash receipts decline under the assumption of average weather resulting in a squeeze to Missouri producers’ bottom line. Missouri follows the national projection for a downward trend in the near term.”

In the report, a 14% decrease in net farm income is forecasted to occur across the state’s agriculture industry this year, compared to a projected 19% decrease in U.S. net farm income.  

The report’s key predictions include:

  • Crop receipts are projected to decrease by $430 million in 2023. Statewide-planted acres sit at 14 million with soybeans making up nearly 6 million acres. Corn-planted area remains flat while hay-, wheat- and rice-planted acres experience slight increases from 2022 to 2023.
  • Livestock receipts are expected to decrease by $400 million in 2023.
  • Inventories for cattle, hogs and poultry make a rebound from 2022.
  • Production expenses are forecast to increase by $230 million in 2023, despite a slight decline in fertilizer, feed and fuel costs.

“RaFF’s state-level insights are critical for decisionmakers,” said Brown, who is also an associate extension professor of markets and policy in the College of Food, Agriculture and Natural Resources. “By understanding how farmers’ and rural communities’ incomes are impacted by various factors, these individuals can be equipped with insights for program and policy discussions.”

Editor’s Note: The Missouri Farm Income Outlook and all associated data tables are available on the center’s website.

About RaFF: The MU Farm and Rural Finance Policy Analysis Center (RaFF) is a Congressionally funded research policy center that implements objective analysis to inform decisionmakers on issues affecting farm and rural finances using a network of state and regional experts and state farm income models. Learn more online at ruralandfarmfinance.com.


Fentanyl can be weaponized. Preparation could minimize the damage.


Peer-Reviewed Publication

RUTGERS UNIVERSITY

The widely-available drug fentanyl, already the number one killer of Americans under 50, could be weaponized and used for terroristic mass poisoning, according to health experts at Rutgers and other institutions.

“Before fentanyl, the only viable mass poisons were rare and difficult-to-access agents such as cyanide or nerve agents,” said Lewis Nelson, chair of the Department of Emergency Medicine at Rutgers New Jersey Medical School and senior author of the new Frontiers in Public Health paper. “Fentanyl can be just as deadly if properly disseminated, and it’s ubiquitous. A motivated person could readily obtain enough to potentially poison hundreds of people — which, uncut, would fit easily onto a teaspoon.”

Unlike biological attacks, in which a weaponized disease could spread globally and kill millions, chemical attacks generally only harm the victim through direct exposure. Still, fentanyl’s high toxicity makes it a viable tool for unleashing a damaging, intentional event on an unsuspecting population.

Attackers with little technical knowledge could introduce the synthetic opioid in fatal doses into building ventilation systems or local food or water supplies. Nelson said it’s unlikely to be successful in a large-scale attack, so simply dumping a truckload in a reservoir would be unlikely to produce significant casualties.

History vividly demonstrates its potential as an aerosolized, inhaled poison. Russian authorities seem to have weaponized a fentanyl-like drug in 2002, after Chechen terrorists seized a crowded theater and threatened to execute hundreds of hostages unless Russia withdrew from Chechnya.

Conventional rescue operations against 40 well-armed and well-fortified captors appeared impossible, so security forces pumped a fentanyl analog into the theater’s ventilation system, incapacitating nearly everyone inside. They then stormed the building, shot the unconscious terrorists, and brought the hostages for medical care.

The operation left 130 hostages dead and demonstrated the scale of harm that is possible when fentanyl is used for non-peaceful purposes.

“We have no effective antidotes to many poisons, but we do have an antidote to fentanyl poisoning — naloxone, which also goes by the brand name Narcan — and the extreme frequency of unintentional fentanyl overdoses means we now stock this antidote in large quantities at health care facilities and pharmacies,” Nelson said.

The frequency of accidental overdose also means that many healthcare providers and non-medical personnel have learned to recognize the signs of fentanyl poisoning while there is still time to reverse it. The paper’s plan for minimizing vulnerability to fentanyl attacks calls for training more caregivers to spot victims quickly and administer naloxone early.

“Treating based on clinical findings rather than more definitive tests such as blood-test results is generally safe,” Nelson said. “If you suspect fentanyl poisoning, administer naloxone, and it turns out the poison was another agent, you generally haven’t hurt the patient.”

The panel’s response plan relies largely on such preparatory steps: training more people to recognize poisoning, creating channels to report unusual victims of fentanyl poisoning, finding commonalities among these victims, and eliminating the sources for obtaining fentanyl. It also involves devising ways to quickly transfer many doses of naloxone to where they are needed most.

“We have a lot of naloxone available in metropolitan and rural areas,” said Nelson. He noted that it’s safe to aid poisoning victims because fentanyl powder must be inhaled or ingested to hurt rescuers, and this is exceedingly unlikely to occur. There is essentially no risk of rapid absorption across the skin. “The key in a mass event will be quickly moving naloxone to the scene or to facilities that are suddenly overwhelmed with victims. Fentanyl generally kills more slowly than poisons like cyanide, but it still requires quick action to prevent harm.”

New research may explain why, despite “the munchies”, frequent cannabis users are leaner than non-users


Peer-Reviewed Publication

UNIVERSITY OF CALIFORNIA - IRVINE

Daniele Piomelli, PhD 

IMAGE: DANIELE PIOMELLI, PHD, DIRECTOR FOR THE UCI CENTER FOR THE STUDY OF CANNABIS, THE LOUISE TURNER ARNOLD CHAIR IN THE NUEROSCIENCES, PROFESSOR IN THE UCI SCHOOL OF MEDICINE DEPARTMENT OF ANATOMY & NEUROBIOLOGY, AND CORRESPONDING AUTHOR FOR THE STUDY. view more 

CREDIT: UCI SCHOOL OF MEDICINE

Irvine, CA – June 1, 2023 – Despite getting “the munchies”, people who frequently use cannabis are leaner and less prone to diabetes than those who don’t. University of California, Irvine researchers have now uncovered a possible explanation for this paradox – and it’s not good news. The findings are reported in a new study titled, “Adolescent exposure to low-dose THC disrupts energy balance and adipose organ homeostasis in adulthood,” published today in Cell Metabolism.

Many adults who consume cannabis daily or almost daily begin using the drug when they are teenagers. During this time of rapid physical development, the new study shows, cannabis can wreak havoc in the fine-tuned processes that govern energy storage, making the body leaner and less susceptible to obesity but also less capable of mobilizing stored nutrients needed for brain and muscle activity. These alterations are rooted in striking molecular changes that occur within the body’s fat depots – also known as the adipose organ – which after exposure to cannabis start making proteins that are normally found only in muscle and the heart.

Researchers gave low daily doses of THC or its vehicle to adolescent mice. They then stopped the treatment and, after the animals had reached adulthood, carried out a thorough assessment of the animals’ metabolism. The results were surprising. Mice that had been treated as adolescents with THC, but were now drug-free, had reduced fat mass and increased lean mass, were partially resistant to obesity and hyperglycemia, had higher-than-normal body temperature, and were unable to mobilize fuel from fat stores. Several of these features are also seen in people who frequently use cannabis.

To make sense of these data, the researchers dove into the molecular changes caused by THC. What they uncovered was even more surprising: fat cells of mice treated with THC looked normal at the microscope but produced large amounts of muscle proteins, which are normally not found in fat. Muscle, on the other hand, made fewer of those same proteins. The researchers concluded that the effort required to make these ‘alien’ proteins interferes with the healthy functioning of fat cells and thus with their ability to store and release stored nutrients. This may in turn affect not only physical activity but also mental processes, such as attention, which depend on a steady influx of fuel to the brain.

“All too often we think of cannabis only as a psychoactive drug,” said Daniele Piomelli, PhD, director for the UCI Center for the Study of Cannabis, the Louise Turner Arnold Chair in the Nuerosciences, and professor in the UCI School of Medicine Department of Anatomy & Neurobiology, “But, its effects extend well beyond the brain. Its main constituent, THC, mimics a group of chemical messengers called endocannabinoids, which regulate important functions throughout the body. Our results show that interfering with endocannabinoid signaling during adolescence disrupts adipose organ function in a permanent way, with potentially far-reaching consequences on physical and mental health.”

The study was primarily funded by the National Institute on Drug Abuse.

UCI School of Medicine:

Each year, the UCI School of Medicine educates more than 400 medical students and nearly 150 PhD and MS students. More than 700 residents and fellows are trained at the UCI Medical Center and affiliated institutions. Multiple MD, PhD and MS degrees are offered. Students are encouraged to pursue an expansive range of interests and options. For medical students, there are numerous concurrent dual degree programs, including an MD/MBA, MD/MPH, or an MD/MS degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Program in Medical Education for Leadership Education to Advance Diversity-African, Black and Caribbean (PRIME LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit medschool.uci.edu.