Publisher Health

The mechanisms by which antidepressants and other emotion-focused medications work could be reconsidered due to an important new breakthrough in the understanding of how the gut communicates with the brain.
New research led by Flinders University has uncovered major developments in understanding how the gut communicates with the brain, which could have a profound impact on the make-up and use of medications such as antidepressants.
“The gut-brain axis consists of complex bidirectional neural communication pathway between the brain and the gut, which links emotional and cognitive centres of the brain,” says Professor Nick Spencer from the College of Medicine and Public Health.
“As part of the gut-brain axis, vagal sensory nerves relay a variety of signals from the gut to the brain that play an important role in mental health and wellbeing.
“The mechanisms by which vagal sensory nerve endings in the gut wall are activated has been a major mystery but remains of great interest to medical science and potential treatments for mental health and wellbeing.”
Serotonin is a major hormone and neurotransmitter in the body and has been shown to play a major role in a range of bodily functions, including mental health and depression.
“The vast majority of serotonin is made in the gut in specialised cells, called enteroendocrine cells (EECs), within the gut wall but we still don’t understand how serotonin released from EECs activates the sensory nerve endings of the vagus nerve,” says Professor Spencer.

“It had once been proposed that EECs make physical synaptic connections with the sensory nerve endings of the vagus and use fast neurotransmitters to activate vagal sensory endings.
“However, the results of our new research uncover that any substances (including serotonin) released from EEC cells must communicate via a process of diffusion to the sensory nerve endings of the vagus nerve, that lie in colon (large intestine).
“We found that the distances between individual EECs that contain serotonin and vagal afferent nerve endings were too far apart to occur via a mechanism that involved synaptic communication and fast neurotransmission, as was previously thought.
“This is a major discovery for our understanding of gut-brain communication which has profound implications for drug developments, treatments of anxiety and depression and other digestive problems such as irritable bowel symptom (IBS), all of which involve serotonin in some way.
“It opens a whole new way of thinking and scientific enquiry for future drug development and investigation for control of the gut-brain axis and potential treatments for mental health and wellbeing, for instance the use of selective serotonin reuptake inhibitors (SSRIs), a widely used type of antidepressant,” he says.
“The majority of serotonin in the body, around 95%, originates in the gut, so there is great interest in how such large quantities of serotonin released from EEC cells act on the vagal sensory nerve endings in the gut wall.

“Understanding this mechanism can provide major new clues as to how serotonin not only communicates along the gut-brain axis, but how this serotonin may be involved in the control of health and wellbeing,” he says.
“Up until now, how different substances (like serotonin) released from EECs activated vagal nerve endings in the gut has been unresolved. Recent literature suggests that that this communication occurred through physical connections known as synapses, and that EEC cells form very close junctions with vagal sensory endings.
“Our findings show that any substances released from EECs must act via diffusion onto vagal sensory nerve endings in the colon, which then relay sensory information to the brain,” says Professor Spencer.
Synaptic transmission is the process by which neurotransmitters communicate with a target cell or cells, for example another neuron(s) or muscle cell(s), via a specialised structure known as the synapse. This involves the neurotransmitter molecules crossing a very short distance to their target cell(s).
Diffusion is the net movement of molecules from one region to another that can occur over any distance.
The researchers used an intricate method of anterograde neuronal tracing from the sensory nerve cell bodies of the vagus nerve, which lie just outside the brain, but send their long nerve projections (axons) all the way down to the small intestine and proximal part of the colon.
“The mean distances between vagal nerve endings and the nearest serotonin containing EECs were hundreds of times greater than known distances that underlie synaptic transmission in vertebrates. This rules out any possible mechanism of fast synaptic transmission,” says Professor Spencer.
“The absence of any close physical contacts between serotonin-containing EECs and vagal nerve endings in our studies leads to the inescapable conclusion that the mechanism by which serotonin activates the sensory nerve endings of the vagus nerve is by diffusion.
“What the findings confirm is that substances released from EECs must communicate via diffusion to activate vagal sensory nerve endings.
“Our understanding of how the gut communicates with the brain, via sensory nerves has been substantially improved based on the findings of this study, and we look forward to exploring this topic further,” he adds.

A report from the world’s leading scientific and medical experts on hormone-related health conditions raises new concerns about the profound threats to human health from endocrine disrupting chemicals (EDCs) that are ubiquitous in our surroundings and everyday lives.
The report, “Endocrine Disrupting Chemicals: Threats to Human Health” provides a comprehensive update on the state of the science around EDCs, with increasing evidence that this large group of toxic substances may be implicated in rising global health concerns.
The report from the Endocrine Society, co-produced with the International Pollutants Elimination Network (IPEN), includes detailed analyses on exposure to EDCs from four sources: plastics, pesticides, consumer products (including children’s products), and per-and polyfluoroalkyl substances (PFAS), a class of thousands of chemicals known or suspected to be EDCs.
The Endocrine Society-IPEN report is being released during the U.N. Environment Assembly (UNEA-6) meeting in Nairobi. At UNEA key agenda items include welcoming the newly adopted Global Framework on Chemicals, advancing global action on highly hazardous pesticides, and threats to the circular economy from plastics and toxic chemicals. The groups’ report anticipates an update from UNEP and the WHO expected later this year on their 2012 Report on State of the Science of Endocrine Disrupting Chemicals.
“A well-established body of scientific research indicates that endocrine-disrupting chemicals that are part of our daily lives are making us more susceptible to reproductive disorders, cancer, diabetes, obesity, heart disease, and other serious health conditions,” said the report’s lead author, Andrea C. Gore, PhD, of the University of Texas at Austin. Gore is also a member of the Endocrine Society’s Board of Directors. “These chemicals pose particularly serious risks to pregnant women and children. Now is the time for the UN Environment Assembly and other global policymakers to take action to address this threat to public health.”
Hormones are natural chemicals that contribute to normal development, adaptation, and maintenance of bodily processes and health. By interfering with hormones and their actions, EDC exposure can impact many health-related functions, with consequences for increased risks of many serious conditions. Evidence suggests that EDCs in the environment contribute to disorders such as diabetes, neurological disorders, reproductive disorders, inflammation, and compromised immune functioning.
Two of the four analyses in the report look at EDCs used in plastics and as pesticides. Global production of plastics and pesticides is increasing even as scientists warn that chemical and plastic pollution is an escalating crisis. Glyphosate is the world’s most widely used herbicide, and a recent study found that glyphosate has eight of ten key characteristics of an EDC. Other studies have found links between glyphosate and adverse reproductive health outcomes. Plastics are made with thousands of known toxic substances, some of which are known or suspected EDCs. The report examines bisphenols and phthalates, two toxic chemical groups found in many plastics. Exposures to EDCs from plastics occur at all phases of plastics production, use, disposal, and even from recycled plastics.
The Endocrine Society-IPEN report notes that, while evidence of health threats from EDCs is mounting, current regulations have not kept pace. “EDCs are different than other toxic chemicals, but most regulations fail to address these differences,” said IPEN Science Advisor Sara Brosché, Ph.D. “For example, we know that even very low doses of endocrine disrupting chemicals can cause health problems and there may be no safe dose for exposure to EDCs. However, regulations typically do not protect against low-dose effects. We need a global approach to controlling EDCs based on the latest science with a goal of protecting the human right to a healthy environment.”
At the UNEA-6 meeting, IPEN is also releasing a new report on “The Global Threat from Highly Hazardous Pesticides,” highlighting ongoing health and environmental risks from HHPs, especially in low- and middle-income countries. DDT, glyphosate, and chorpyrifos, three HHPs reviewed in the Endocrine Society report, are also highlighted in the new IPEN report as they continue to pose health threats especially in the Global South.
In addition to plastics and pesticides, the report looks at EDC exposures from arsenic and lead, and from widely used per- and polyfluoroalkyl substances (PFAS), humanmade “forever chemicals” used as oil and water repellents and coatings. Lead remains in use in paint in many countries, as documented in recent IPEN reports. Endocrine-related conditions from lead exposure may include delayed onset of puberty and early menopause. Arsenic is a common metal that has long been linked to cancer and other health conditions, and more recent evidence shows that arsenic can disrupt multiple endocrine systems. PFAS are used in hundreds of products including clothing and food packaging, but recent studies show that some PFAS can disrupt hormones such as estrogen and testosterone and impair thyroid hormone functions.

The first stem cell culture method that produces a full model of the early stages of the human central nervous system has been developed by a team of engineers and biologists at the University of Michigan, the Weizmann Institute of Science, and the University of Pennsylvania.
“Models like this will open doors for fundamental research to understand early development of the human central nervous system and how it could go wrong in different disorders,” said Jianping Fu, U-M professor of mechanical engineering and corresponding author of the study in Nature.
The system is an example of a 3D human organoid — stem cell cultures that reflect key structural and functional properties of human organ systems but are partial or otherwise imperfect copies.
“We try to understand not only the basic biology of human brain development, but also diseases — why we have brain-related diseases, their pathology, and how we can come up with effective strategies to treat them,” said Guo-Li Ming, who along with Hongjun Song, both Perelman Professors of Neuroscience at UPenn and co-authors of the study, developed protocols for growing and guiding the cells and characterized the structural and cellular characteristics of the model.
For example, organoids developed using patient-derived stem cells may be used for identifying which drugs offer the most successful treatment. Already, human brain and spinal cord organoids are used to study neurological and neuropsychiatric diseases, but they often mimic one part of the central nervous system and are disorganized. The new model, in contrast, recapitulates the development of all three sections of embryonic brain and spinal cord simultaneously, a feat that has not been achieved in previous models.
“The system itself is really groundbreaking,” said Orly Reiner, the Berstein-Mason Professorial Chair of Neurochemistry at Weizmann and co-author of the study who developed cellular tools to identify neural cell types in the model. “A model that mimics this structure and organization has not been done before, and it offers numerous possibilities for studying human brain development and especially developmental brain diseases.”
While the model is faithful to many aspects of the early development of the brain and spinal cord, the team notes several important differences. For one, neural tube formation — the very first stage of central nervous system development — is very different. The model can’t be used to simulate disorders that stem from improper closure of the neural tube such as spina bifida.

Instead, the model started with a row of stem cells roughly the size of the neural tube found in a 4-week-old embryo — about 4 millimeters long and 0.2 millimeters in width. The team stuck the cells to a chip patterned with tiny channels that the team used to introduce materials that enabled the stem cells to grow and guided them toward building a central nervous system.
The team then added a gel that allowed the cells to grow in three dimensions and chemical signals that nudged them to become the precursors of neural cells. In response, the cells formed a tubular structure. Next, the team introduced chemical signals that helped the cells identify where they were within the structure and progress to more specialized cell types. As a result, the system organized itself to mimic the forebrain, midbrain, hindbrain and spinal cord in a way that mirrors embryonic development.
“As an engineer, the challenging part is to learn neural development and stem cell biology,” said Xufeng Xue, first author of the study and a postdoctoral fellow in mechanical engineering U-M. “It was a team effort to make this happen, with amazing collaborators at UPenn and Weizmann.”
The team grew the cells for 40 days, simulating development of the central nervous system to about 11 weeks post-fertilization. In this time, the team was able to demonstrate the roles of specific genes in spinal cord development and learn how certain cell types in the early human nervous system differentiate into different cells with specialized functions.
“In many cases, animal models simply do not recapitulate either the characteristics or the degree of severity seen in human brain diseases such as microcephaly,” Song said. “Even nonhuman primates are not the same. So in the context of disease biology and treatment strategies, a human cell model is almost irreplaceable.”
The team plans to apply the model to study different human brain diseases using patient derived stem cells.

Xue hopes to continue using this model to study the interplay among different parts of the brain during development. He is also interested in studying how the brain sends instructions for movement via the spinal cord. This line of inquiry, which could shed new light on disorders like paralysis, would require the neurons to link up into working circuits — something that was not observed in this study.
Insoo Hyun, a bioethicist at the Museum of Science in Boston who was not part of the study, notes that experiments like these are closely scrutinized before they are allowed to move forward.
“Research groups must be clear about the scientific question they are trying to answer — and that the degree of development they allow in the model is the minimum to answer the question,” he said.
The model does not include peripheral nerves or functioning neural circuitry — features that are critical for humans’ ability to experience our environment and process that experience.
The study was funded by the Michigan-Cambridge Collaboration Initiative, University of Michigan, State of Michigan, Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, National Science Foundation and National Institutes of Health.
The research conforms to the 2021 Guidelines for Stem Cell Research and Clinical Translation recommended by the International Society for Stem Cell Research. All protocols used in this work were approved by the Human Pluripotent Stem Cell Research Oversight Committee at the University of Michigan, Ann Arbor.
The team has applied for patent protection with the assistance of U-M Innovation Partnerships and is seeking partners to bring the technology to market.

A long-term analysis conducted by leading microbiologists at the Icahn School of Medicine at Mount Sinai reveals that antibody responses induced by COVID-19 vaccines are long-lasting. The study results, published online in the journal Immunity on February 22, challenge the idea that mRNA-based vaccine immunity wanes quickly.
The emergence of SARS-CoV-2, the virus that causes COVID-19, in late 2019 sparked the global pandemic that is now in its fifth year. Vaccines that were developed at record speed have saved millions of lives. However, the emergence of SARS-CoV-2 variants and waning immunity have decreased the effectiveness of the vaccines against symptomatic disease. The common perception now is that mRNA-based vaccine-induced immunity wanes quickly. However, this assumption is largely based on data from short-term studies that include a very limited number of data points following peak responses.
The Mount Sinai research team’s analysis of more than 8,000 samples collected over a three-year period in New York City examined how antibody responses to the virus’s spike protein changed after infections, during the primary immunization series, during monovalent and bivalent booster vaccination, and during breakthrough infections.
They found that upon primary immunization, participants with pre-existing immunity (those who had previously been infected with the virus) mounted higher antibody responses faster and achieved higher steady-state antibody titers than individuals who had not been previously infected. The waning of antibody response was characterized by two phases: an initial rapid decay from the strong peak after vaccination, followed by a stabilization phase with very slow decay, suggesting that antibody levels were very long-lasting. Booster vaccination equalized the differences in antibody concentration between participants with and without pre-existing immunity. Breakthrough infections increased antibodies to similar levels as an additional vaccine dose in individuals who had not previously been infected.
This investigation represents one of the most extensive and in-depth assessments of the longevity of SARS-CoV-2 immune responses to date. Its major conclusion is that changes in the virus that allow it to evade immunity, rather than waning immunity, are the major reason for breakthrough infections.
“Ours is one of the longest-running COVID-19 studies out there,” said Viviana Simon, MD, PhD, Professor of Microbiology, Medicine and Pathology, Molecular and Cell-Based Medicine, at Icahn Mount Sinai and lead author of the paper. “Following the same group of people monthly over time is rare and powerful because you can compare immune responses on an individual level. SARS-CoV-2 continues to evolve, so this research is important to provide an understanding about the impact of new variants and new vaccine doses on a healthy immune system, and to guide all of us to make the best choices to maintain protection against the virus that continues to circulate in our communities.”
This in-depth analysis was made possible through the Protection Associated with Rapid Immunity to SARS-CoV-2 (PARIS) study, an observational, longitudinal cohort of health care workers of the Mount Sinai Health System that was initiated in April 2020. At that time, the densely populated New York metropolitan area was hit with an exponential increase in severe SARS-CoV-2 infections, and essential workers in the health care system were at high risk for infection. In response to the crisis, a team of leading virologists, physician-scientists, and pathologists at Mount Sinai established a specific and sensitive SARS-CoV-2 binding enzyme-linked immunosorbent assay to accurately measure the SARS-CoV-2 antibody titers. This test was used to measure immune responses in the PARIS cohort in order to determine how quickly the antibody defenses were mounted and much these changed over the months and years of follow up.

In addition to showing the impact on a person’s individual antibody response to vaccines based on the type of vaccine received and whether or not they were infected before receiving the first dose, the PARIS study made possible the development of a mathematical model that can be used to predict and characterize antibody responses of both individual people and populations.
“People have pandemic fatigue and vaccine uptake has slowed, especially after the vaccines started to be charged to insurance,” said Komal Srivastava, MS, Director of Strategy and Operation of the Mount Sinai Center for Vaccine Research and Pandemic Preparedness and co-first author of the paper. “We were pleasantly surprised to see that the booster doses promoted a large antibody response regardless of a person’s personal infection history, so we are hopeful that our study findings will encourage people to get their vaccine boosters when eligible and to stay engaged in research. Our work also showcases the impact of viral evolution over time and why it’s critical to keep studies like this going, despite the pandemic fatigue.”
According to the research team, the PARIS model has broad applications for studying the kinetics of antibodies produced to different COVID-19 vaccines in diverse populations. They stress much more work remains to analyze side effects, applications of the antibody model and continued research about new vaccines and viral variants.
“This study adds an essential piece of data to understand the intricate immune response elicited by SARS-CoV-2 infection and COVID-19 vaccination,” says Juan Manuel Carreno Quiroz, PhD, Assistant Professor in the Department of Microbiology and co-first author of the paper. “In light of the emerging viral variants, which predominantly induce a cross-reactive antibody response against the spike protein, it will be exciting to characterize in depth the role of these antibodies — in particular the non-neutralizing ones — in protection against the most recent circulating viral variants. Likewise, monitoring the induction of variant-specific antibodies after multiple exposures by breakthrough infections and by administration of updated COVID-19 vaccines, such as the XBB.1.5 monovalent booster, will be key to understand the evolution of the antibody response over time.”

As climate changes, temperature isn’t the only factor to influence the spread of infectious diseases. Humidity plays a role, too, according to new research published this week (Feb. 25) in Ecology Letters. The international team, led by Penn State researchers, developed a model to examine how parasitic worms, specifically species that infect livestock and wildlife, respond to changes in temperature and humidity and how those variables may shape the risk of infection and the development of new hot spots in the future. The findings, which may suggest similar behavior among worms that infect humans, could guide improvements in livestock management and public health interventions in endemic areas.
“We need to understand how climate change can affect the future of these infections,” said Isabella Cattadori, professor of biology at Penn State and senior author of the study. “Are they going to get worse? Are they going to shift into different habitats and create new hotspots? Will they mutate and develop into more pathogenic infections?”
Parasitic worms, specifically soil-transmitted helminths, are common and infect roughly 25% of the global human population, according to theWorld Health Organization. They’re also a major source of infection in animals, causing large economic loss to the livestock industry. Yet, Cattadori said, studies on climate and infections typically look at diseases carried by vectors like mosquitoes and ticks.
“There isn’t much attention on helminth infections because they’re not as threatening as vector-borne diseases, and people tend to underestimate the importance of worm infections,” Cattadori said, further explaining that most studies focus on temperature, and few consider other climate-related variables, like humidity, as drivers of infection.
The lifecycle of soil-transmitted helminths has two phases — a free-living stage as eggs and larvae in the environment and an adult stage inside the host. Researchers sought to understand how the free-living stages were affected by climate. They reviewed current scientific literature to gather data on the effect of temperature and relative humidity on helminth egg and larval stages of nine species of helminth that commonly infect livestock and wildlife. These species were then divided into two groups depending on where they reside in their host: worms that live in the stomach and worms that live in the intestines.
Based on this information, they developed a mathematical model to describe how helminth hatching, development and mortality of each helminth group responds to temperature and humidity. They then applied this model to look at historical and future projections of infection risk under different climate change scenarios across Southern, Central and Northern Europe. For future projections, they considered short-term, from 2041 to 2060, and long-term, from 2081 to 2100, scenarios.
“We didn’t just look at correlation or linear relationships between variables. We disentangled how each component of the free-living stages is affected by climatic conditions, developing a mechanistic understanding of how helminths respond to these environmental stressors,” said Chiara Vanalli, postdoctoral scholar at Penn State and lead author of the study, which she conducted as a graduate student in Cattadori’s lab. “This is essential for understanding what might happen in the future.”
The study is one of the first, Cattadori said, to look at the interaction between multiple climate variables across multiple parasitic worm species to understand how these factors may alter the seasonal profile of disease transmission, as well as when and where these patterns might arise.

Researchers discovered that not all parasite species behave the same way. Those that reside in the host’s intestines were strongly affected by temperature, reaching the highest risk of infection at 50 degrees Fahrenheit. On the other hand, helminths that reside in the stomach responded strongly to humidity, reaching their peak when humidity was 80% or higher. When researchers looked at the seasonality in these patterns across Europe, they found that historically, infection risk has one or two peaks in the spring and summer for the intestinal group and one peak for the stomach group. However, in the future, they expect these peaks may change.
“The intensity of these peaks and the way they shift will depend on location and specific climatic conditions as well as helminth species type,” Vanalli said. A two-season trend, with one peak in spring and one in fall, is expected to intensify for intestinal helminths while stomach helminths may be more likely to maintain the summer peak, especially at northern regions.
Researchers also considered how spatial distribution may change too. Historically, infection risk is low in Northern Europe. However, when researchers looked into the future, they found that infection hot spots will shift north, facilitated by increasingly milder climate in central and northern regions while southern regions will undergo more extreme temperature and drier conditions. Over the long-term, Scandinavian countries are projected to experience the greatest risk among both groups of helminths, up to an increase of 100% for the intestinal species and 55% for the stomach species compared to the rest of the continent. What’s more, the drastic increase in infection risk at mid-to-high latitudes may likely intensify the risk of co-infection since multiple species of helminths could thrive together.
With a better understanding of how animals are exposed to these infections and potential changes in the future, the findings could lead to the development of better livestock management and preventative control strategies, the researchers said. The dynamics described by the researchers could also shed light on the potential risk for human health because some of the family groups studied include parasites that also affect humans.
“We need to start thinking about how to adapt our strategies to a world where climate is changing,” Cattadori said.
Cattadori is also affiliated with the Center for Infectious Disease Dynamics in the Penn State Huck Institutes of the Life Sciences. Other authors on the paper are Marino Gatto, Lorenzo Mari and Renato Casagrandi, all faculty in the Department of Electronics, Information and Bioengineering at Politecnico di Milano.
Funds from the Huck Institutes of the Life Sciences and the Eberly College of Science supported this work.

Black carbon is the most dangerous air pollutant you’ve never heard of. Its two main sources, diesel exhaust and wood smoke from wildfires and household heating, produce ultrafine air particles that are up to 25 times more of a health hazard per unit compared to other types of particulate matter. Despite its danger, black carbon is understudied due to a lack of monitoring equipment. Regulatory-standard sensors are wildly expensive to deploy and maintain, resulting in sparse coverage in regions infamous for poor air quality, such as the greater Salt Lake City metropolitan area in Utah.
A University of Utah-led study found that the AethLabs microAeth MA350, a portable, more affordable sensor, recorded black carbon concentrations as accurately as the Aerosol Magee Scientific AE33, the most widely used instrument for monitoring black carbon in real time. Researchers placed the portable technology next to an existing regulatory sensor at the Bountiful Utah Division of Air Quality site from Aug. 30, 2021-Aug. 8, 2022. The AethLabs technology recorded nearly identical quantities of black carbon at the daily, monthly and seasonal timescales. The authors also showed that the microAeth could distinguish between wildfire and traffic sources as well as the AE33 at longer timescales.
Because black carbon stays close to the source, equipment must be localized to yield accurate readings. The microAethsensor’s portability would allow monitoring at remote or inaccessible stationary sites, as well as for mobile use.
“Having a better idea of black carbon exposure across different areas is an environmental justice issue,” said Daniel Mendoza, research assistant professor of atmospheric sciences at the University of Utah and lead author of the study. “The Salt Lake Valley’s westside has some of the region’s worst air quality partly because it’s closest to pollution sources, but we lack the ability to measure black carbon concentrations accurately. Democratizing data with reliable and robust sensors is an important first step to safeguarding all communities from hazardous air pollution.”
The study was published on Feb. 1, 2024, in the journal Sensors.
In the dark
Black carbon pollutants are a type of fine particulate matter (PM2.5), a class of air particles small enough to be inhaled into the lungs and absorbed into the bloodstream. Black carbon is true soot, produced when hydrocarbons do not fully burn, and has been shown to migrate into the heart, brain, fetal tissue, and other biological systems.

“The combination of increasing wildfires driven by anthropogenic climate change and steady population growth along the Wasatch Front in coming decades will result in new pollution challenges that Utah will have to face,” said Erik Crosman, assistant professor of environmental sciences at West Texas A&M University and a co-author of the study.”The portable MA350 ‘micro’ aethalometer could be utilized in building a better spatial observational network of accurate but lower cost black carbon sensors across the region.”
Though research suggests exposure to black carbon is 10 to 25 times more hazardous to respiratory and cardiovascular health than other PM2.5, long-term health outcomes are largely unknown. An accurate observation network is the first step to establishing disease risk and creating effective public health policies. This study, funded by the Salt Lake City Corporation, aims to help regions with poor air quality establish a baseline of black carbon distribution.
“It’s crucial that we target our measurements to identify the largest and most relevant black carbon sources,” said Drew Hill, a study coauthor who leads data science and applied research work at AethLabs. “We’ve added a feature rooted in physical principles to provide real-time estimates of the amount of measured black carbon produced by fossil fuel burning versus wood burning to allow researchers and policy makers to triangulate such sources.”
Having established the portable sensor’s accuracy and regional relevance, the researchers are measuring black carbon levels around the Salt Lake Valley, including testing concentrations present inside school buildings.
“First, you need to get readings. In some neighborhoods you could look at air quality concentrations, then look at the cancer or other disease rate in that neighborhood,” said Mendoza, who is also an adjunct assistant professor in the Division of Pulmonary Medicine at University of Utah Health. “Getting measurements with a high degree of accuracy, now we can really think about health and policy avenues to really protect everyone’s lung health.”

Inspired by the design of space shuttles, Penn Engineering researchers have invented a new way to synthesize a key component of lipid nanoparticles (LNPs), the revolutionary delivery vehicle for mRNA treatments including the Pfizer-BioNTech and Moderna COVID-19 vaccines, simplifying the manufacture of LNPs while boosting their efficacy at delivering mRNA to cells for medicinal purposes.
In a paper in Nature Communications, Michael J. Mitchell, Associate Professor in the Department of Bioengineering, describes a new way to synthesize ionizable lipidoids, key chemical components of LNPs that help protect and deliver medicinal payloads. For this paper, Mitchell and his coauthors tested delivery of an mRNA drug for treating obesity and gene-editing tools for treating genetic disease.
Previous experiments have shown that lipidoids with branched tails perform better at delivering mRNA to cells, but the methods for creating these molecules are time- and cost-intensive. “We offer a novel construction strategy for rapid and cost-efficient synthesis of these lipidoids,” says Xuexiang Han, a postdoctoral student in the Mitchell Lab and the paper’s co-first author.
The method involves combining three chemicals: an amine “head,” two alkyl epoxide “tails” and, finally, two acyl chloride “branched tails.” The completed lipidoid’s resemblance to a space shuttle strapped to two booster rockets is not coincidental: in college, recalls Han, a documentary about the space shuttle left him impressed with the design of solid rocket boosters that enabled the shuttle to enter orbit. “I figured that we could append two branch tails as ‘boosters’ into the lipidoid to promote the delivery of mRNA,” says Han.
Indeed, the addition of the branched tails led to a striking increase in the ability of LNPs equipped with the new lipidoid to deliver mRNA to target cells, much like a rocket whose boosters allow it to more easily penetrate the atmosphere. “We saw a dramatic increase of a hormone that regulates metabolism to target cells after delivering mRNA using these lipidoids, which is really exciting when you consider it as a way to treat obesity,” says Mitchell.
This study was conducted at the University of Pennsylvania School of Engineering and Applied Science and supported by the National Institutes of Health (Award DP2 TR002776); Burroughs Wellcome Fund Career Award at the Scientific Interface; National Science Foundation CAREER Award (CBET-2145491) and the American Cancer Society (Grant RSG-22-122-01-ET).
Other co-authors include Junchao Xu, Lulu Xue, Ningqiang Gong and Rohan Palanki from Penn Engineering; Mohamad-Gabriel Alameh, Rakan El-Mayta, Claude C. Warzecha, James M. Wilson and Drew Weissman in the Perelman School of Medicine at Penn; Gan Zhao and Andrew E. Vaughan from Penn Vet; and Ying Xu of Case Western Reserve University.

The field of biomedical engineering anticipates an amazing future for the field, its researchers, and students.
IEEE, the world’s largest technical professional organization dedicated to advancing technology for humanity, and the IEEE Engineering in Medicine and Biology Society (IEEE EMBS), recently published a detailed position paper on the field of biomedical engineering titled, “Grand Challenges at the Interface of Engineering and Medicine.” The paper, published in the IEEE Open Journal of Engineering in Medicine and Biology (IEEE OJEMB), was written by a consortium of 50 renowned researchers from 34 prestigious universities around the world, and lays the foundation for a concerted worldwide effort to achieve technological and medical breakthroughs.
Representing the University of Pittsburgh in the position paper is Sanjeev G. Shroff, Interim U.S. Steel Dean of the Swanson School of Engineering; Distinguished Professor of and Gerald E. McGinnis Chair in Bioengineering; and Professor of Medicine.
“What we’ve accomplished here will serve as a roadmap for groundbreaking research to transform the landscape of medicine in the coming decade,” said Dr. Michael Miller, senior author of the paper and professor and director of the Department of Biomedical Engineering at Johns Hopkins University. “The outcomes of the task force, featuring significant research and training opportunities, are poised to resonate in engineering and medicine for decades to come.”
“Since the founding of our Department of Bioengineering 25 years ago, we have witnessed transformative advances and new technologies developed through partnerships between Pitt’s Swanson School of Engineering, School of Medicine, School of Health and Rehabilitation Sciences, McGowan Institute for Regenerative Medicine, Brain Institute, and the University of Pittsburgh Medical Center (UPMC),” Dr. Shroff said. “The field of biomedical engineering is at a critical juncture in its evolution, with a need to reflect on the past and identify singular challenges that will continue to improve the human condition, These new Grand Challenges, developed through a global debate, will help guide our academic programs and research as well as prepare the next generation of bioengineers.”
The position paper was the result of two years of discussion culminating in a two-day workshop organized by IEEE EMBS and the Department of Biomedical Engineering at Johns Hopkins University and the Department of Bioengineering at the University of California San Diego. Through the course of the workshop, the researchers identified five primary medical challenges that have yet to be addressed, but by solving them with advanced biomedical engineering approaches, can greatly improve human health. By focusing on these five areas, the consortium has laid out a roadmap for future research and funding.
The Five Grand Challenges Facing Biomedical Engineering Bridging precision engineering and precision medicine for personalized physiology avatars In an increasingly digital age, we have technologies that gather immense amounts of data on patients, which clinicians can add to or pull from. Making use of this data to develop accurate models of physiology, called “avatars” — which take into account multimodal measurements and comorbidities, concomitant medications, potential risks and costs — can bridge individual patient data to hyper-personalized care, diagnosis, risk prediction, and treatment. Advanced technologies, such as wearable sensors and digital twins, can provide the basis of a solution to this challenge. The pursuit of on-demand tissue and organ engineering for human health

Tissue engineering is entering a pivotal period in which developing tissues and organs on demand, either as permanent or temporary implants, is becoming a reality. To shepherd the growth of this modality, key advancements in stem cell engineering and manufacturing — along with ancillary technologies such as gene editing — are required. Other forms of stem cell tools, such as organ-on-a-chip technology, can soon be built using a patient’s own cells and can make personalized predictions and serve as “avatars.” Revolutionizing neuroscience using artificial intelligence (AI) to engineer advanced brain-interface systems Using AI, we can analyze the various states of the brain through everyday situations and real-world functioning to noninvasively pinpoint pathological brain function. Creating technology that does this is a monumental task, but one that is increasingly possible. Brain prosthetics, which supplement, replace or augment functions, can relieve the disease burden caused neurological conditions. Additionally, AI modeling of brain anatomy, physiology, and behavior, along with the synthesis of neural organoids, can unravel the complexities of the brain and bring us closer to understanding and treating these diseases. Engineering the immune system for health and wellness With a heightened understanding of the fundamental science governing the immune system, we can strategically make use of the immune system to redesign human cells as therapeutic and medically invaluable technologies. The application of immunotherapy in cancer treatment provides evidence of the integration of engineering principles with innovations in vaccines, genome, epigenome and protein engineering, along with advancements in nanomedicine technology, functional genomics and synthetic transcriptional control. Designing and engineering genomes for organism repurposing and genomic perturbations Despite the rapid advances in genomics in the past few decades, there are obstacles remaining in our ability to engineer genomic DNA. Understanding the design principles of the human genome and its activity can help us create solutions to many different diseases that involve engineering new functionality into human cells, effectively leveraging the epigenome and transcriptome, and building new cell-based therapeutics. Beyond that, there are still major hurdles in gene delivery methods for in vivo gene engineering, in which we see biomedical engineering being a component to the solution to this problem. “This paper represents a major milestone in the advancement of biomedical engineering, which could only have been achieved through close collaboration rather than the work of many siloed individuals,” said consortium member Dr. Metin Akay, founding chair of the Biomedical Engineering Department at the University of Houston and Ambassador of IEEE EMBS. “We have a shared commitment to advancing patient-centric technologies, and healthcare efficacy and accessibility — which extends beyond academic institutions — and elevating healthcare quality, reducing costs and improving lives worldwide.”
“These grand challenges offer unique opportunities that can transform the practice of engineering and medicine,” remarked Dr. Shankar Subramaniam, lead author of the taskforce, distinguished professor, Shu Chien-Gene Lay Department of Bioengineering at the University of California San Diego and past President of IEEE EMBS. “Innovations in the form of multi-scale sensors and devices, creation of humanoid avatars and the development of exceptionally realistic predictive models driven by AI can radically change our lifestyles and response to pathologies. Institutions can revolutionize education in biomedical and engineering, training the greatest minds to engage in the most important problem of all times — human health.”

Results from a large clinical trial funded by the National Institutes of Health show that an intervention for anxiety provided to pregnant women living in Pakistan significantly reduced the likelihood of the women developing moderate-to-severe anxiety, depression, or both six weeks after birth. The unique intervention was administered by non-specialized providers who had the equivalent of a bachelor’s degree in psychology — but no clinical experience. The results suggest this intervention could be an effective way to prevent the development of postpartum mental health challenges in women living in low-resource settings.
“In low resource settings, it can be challenging for women to access mental health care due to a global shortage of trained mental health specialists,” said Joshua A. Gordon, M.D., Ph.D., Director of the National Institute of Mental Health, part of NIH. “This study shows that non-specialists could help to fill this gap, providing care to more women during this critical period.”
Led by Pamela J. Surkan, Ph.D., Sc.D., of Johns Hopkins Bloomberg School of Public Health, Baltimore, the study was conducted in the Punjab Province of Pakistan between April 2019 and January 2022. Pregnant women with symptoms of at least mild anxiety were randomly assigned to receive either routine pregnancy care or a cognitive behavioral therapy (CBT)-based intervention called Happy Mother-Healthy Baby. The researchers assessed the participants (380 women in the CBT group and 375 women in the routine care group) for anxiety and depression six weeks after the birth of their child.
The researchers found that 9% of women in the intervention group developed moderate-to-severe anxiety compared with 27% of women in the routine care group. Additionally, 12% percent of women in the intervention group developed depression compared with 41% of women in the routine care group.
“Postpartum depression not only harms mothers, it is also associated with poorer physical growth and delayed cognitive development in their children,” said Dr. Surkan. “The link between maternal and child health highlights the critical importance of developing effective ways to address postpartum anxiety and depression.”
The Happy Mother-Healthy Baby intervention was created using input from pregnant women in a hospital in Rawalpindi, Pakistan. Pregnant women took part in six intervention sessions where they learned to identify anxious thoughts and behaviors, such as thoughts about possible miscarriage, and to practice replacing them with helpful thoughts and behaviors. The first five sessions were conducted in early to mid-pregnancy, and the sixth session occurred in the third trimester.
Prior research suggests that up to 30% of women in the Global South, which includes South America, Africa, and most of southern Asia, report experiencing anxiety during pregnancy. Anxiety during pregnancy predicts the development of anxiety and depression after birth, making the prenatal period a prime target for intervention. However, it can be challenging for women living in low-resource settings to access trained clinical care. The findings from this study demonstrate that an intervention such as Happy Mother-Healthy Baby could be an effective way to help prevent the development of postpartum depression and anxiety in settings where specialist clinical care may be hard to access.
“In the future, we can build on these findings through implementation research. Having identified an intervention that works, the next step is to figure out the best ways to deliver effective treatment to the people who need it, bridging the gap between science and practice,” said Dr. Surkan.

For nearly a week, people have been waylaid at pharmacies after a unit of the nation’s largest insurer was shut down by a possible ransomware assault.A cyberattack on a unit affiliated with UnitedHealthcare, the nation’s largest insurer, has disrupted drug prescription orders at thousands of pharmacies for nearly a week.The assault on the unit, Change Healthcare, a division of United’s Optum, was discovered last Wednesday. The attack appeared to be by a foreign country, according to two senior federal law enforcement officials, who expressed alarm at the extent of the disruption on Monday.UnitedHealth Group, the conglomerate, said in a federal filing that it had been forced to disconnect some of Change Healthcare’s vast digital network from its clients, and as of Monday, had not been able to restore all of those services.Change handles some 15 billion transactions a year, representing as many as one in three U.S. patient records and involving not just prescriptions but dental, clinical and other medical needs. The company was acquired by UnitedHealth Group for $13 billion in 2022.This latest attack underscores the vulnerability of health care data, especially patients’ personal information, including their private medical records. Hundreds of breaches at hospitals, health plans and doctors’ offices are being investigated, according to federal records.In this case, the disturbance has been widespread, including for U.S. military overseas. Change acts as a digital intermediary to helps pharmacies verify a patient’s insurance coverage for their prescriptions, and some reports indicate that people have been forced to pay in cash.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.