Acetaminophen poisoning is one of the leading causes of hospitalization and death related to non-prescription drugs in the United States, according to Kennon Heard, MD, PhD, a professor in the CU Anschutz Department of Emergency Medicine and the department’s section chief of medical toxicology.

Each year, an estimated 56,000 people visit emergency departments because of acetaminophen poisoning, and about 2,600 are hospitalized. The drug is responsible for nearly half of all acute liver failure cases in the U.S. and roughly 20% of liver transplants nationwide.

Heard has studied acetaminophen poisoning for more than 25 years. He is now helping to lead a long-term clinical trial that is testing a potential new way to reduce liver damage in severe overdose cases. The experimental approach uses a medication typically given to patients poisoned by antifreeze.

Heard says CU and Denver Health, which is home to the Rocky Mountain Poison & Drug Safety center, have played a central role in this research for decades. “have been the center of the acetaminophen research universe for the past 40 years. There’s been a long history of this type of work being done here, and it’s great to be a part of it.”

Why Acetaminophen Overdoses Happen

Acetaminophen is the main ingredient in Tylenol and many store-brand pain relievers used for mild to moderate pain and low-grade fever. It is also included in a wide range of over-the-counter products for colds, flu, sinus symptoms, and menstrual discomfort.

The medication has been used safely for decades when taken according to instructions. Problems arise when people exceed recommended doses, either by taking too much at once or by repeatedly taking more than advised over time.

“There are cases where people accidentally take too much acetaminophen,” Heard says. “Or maybe they have a really bad toothache, and they think if two is good, four is better, eight is even better, and so on. Or it’s someone who’s taking multiple repeated overdoses. Those are the people who get into trouble.”

Overdoses are also frequently linked to suicide and self-harm, Heard notes. “The No. 1 rule at the Poison Center is that if it’s available, people will take it, and a lot of people have Tylenol in their medicine chest.”

Limits of the Standard Antidote

For decades, doctors have relied on a drug called acetylcysteine as an effective antidote for acetaminophen overdose. When given early, it can prevent serious liver damage.

Its effectiveness drops sharply, however, if treatment begins more than eight hours after the overdose.

“The problem is that many patients don’t present with acetaminophen poisoning until after they have liver injury, at which point the acetylcysteine is less effective, and in some cases doesn’t really work at all,” Heard says.

Testing an Antifreeze Antidote

The current clinical trial led by Heard and his colleagues is focused on fomepizole, a drug approved to treat poisoning from ethylene glycol and methanol, substances commonly found in antifreeze. Exposure can occur accidentally, and in some cases people with alcohol use disorder have consumed antifreeze as a substitute for alcohol.

Fomepizole works by blocking enzymes known as alcohol dehydrogenase, stopping the body from converting ethylene glycol and methanol into toxic byproducts.

Heard says interest in using fomepizole for acetaminophen overdose dates back to the 1990s, when he was training in medical toxicology. Evidence came from individual patient case reports and animal studies, particularly in severe overdose cases.

More recently, research has shown that doctors are increasingly using fomepizole off-label to treat serious acetaminophen poisoning.

Richard Dart, MD, PhD, a professor of emergency medicine and Heard’s longtime mentor, ultimately suggested formally testing the drug in a clinical trial. Dart has served as director of Rocky Mountain Poison & Drug Safety since 1992.

A Proof of Concept Clinical Trial

The ongoing phase II trial is designed to determine whether adding fomepizole to standard acetylcysteine treatment can reduce liver damage in patients at high risk after acetaminophen overdose. It is considered a “proof of concept” study to see whether the combination shows enough promise to justify larger trials.

Participants are randomly assigned to receive either both medications or acetylcysteine alone. The study is double-blind, meaning neither the patients nor the researchers know which treatment each participant receives until the trial ends.

“We’ll compare the amount of liver damage, as measured by their liver enzymes, to see whether the fomepizole provides an added protective benefit beyond the standard treatment,” Heard says.

Patients are currently being enrolled at Denver Health, UCHealth University of Colorado Hospital, Children’s Hospital Colorado, and several additional sites. Enrollment has been slow due to the challenge of finding patients who meet the study criteria, but researchers hope to enroll about 40 participants within 12 to 18 months.

If the findings are positive, Heard expects the research to move into a larger trial that would examine longer-term outcomes, including survival and the need for liver transplants.

A Caution for Medicine Cabinets Everywhere

“The message that I would want to get out,” Heard says, is that people should carefully read medication labels, avoid exceeding recommended doses, and recognize that acetaminophen may be present in multiple products at home.

“We’ve started to recognize that the number of people who die from an accidental overdose is pretty close to the number of people who deliberately take an overdose,” he says.

Heard’s collaborators on the study include Dart and Andrew Monte, MD, PhD, also a professor of emergency medicine.

The iron cloud is being reported for the first time in Monthly Notices of the Royal Astronomical Society. It forms a long strip that fits neatly inside the nebula’s inner region, which has an elliptical shape seen in many well known images, including those captured by the James Webb Space Telescope at infrared wavelengths.¹ The structure is immense. Its length is about 500 times greater than Pluto’s orbit around the Sun, and the total amount of iron it contains is roughly equal to the mass of Mars.

What Makes the Ring Nebula Special

The Ring Nebula was first observed in 1779 by French astronomer Charles Messier in the northern constellation Lyra.² It is a glowing shell of gas produced when a star reaches the end of its nuclear fuel burning stage and ejects its outer layers into space. Astronomers expect the Sun to shed its outer material in a similar way several billion years from now.³

How the Iron Bar Was Found

The iron cloud was revealed through observations made with the Large Integral Field Unit (LIFU) mode of a new instrument known as the WHT Enhanced Area Velocity Explorer (WEAVE).⁴ WEAVE is mounted on the Isaac Newton Group’s 4.2-meter William Herschel Telescope.⁵

LIFU is made up of hundreds of optical fibers working together. This setup allowed the researchers to collect spectra (where light is separated into its constituent wavelengths) from every point across the face of the Ring Nebula, covering all optical wavelengths for the first time.

Seeing the Nebula in a New Way

Lead author Dr. Roger Wesson, who is based at both UCL’s Department of Physics & Astronomy and Cardiff University, described how the finding emerged. “Even though the Ring Nebula has been studied using many different telescopes and instruments, WEAVE has allowed us to observe it in a new way, providing so much more detail than before. By obtaining a spectrum continuously across the whole nebula, we can create images of the nebula at any wavelength and determine its chemical composition at any position.

“When we processed the data and scrolled through the images, one thing popped out as clear as anything — this previously unknown ‘bar’ of ionized iron atoms, in the middle of the familiar and iconic ring.”

Competing Ideas About Its Origin

The researchers say the origin of the iron bar is still unknown. More detailed observations will be needed to understand how it formed. One possibility is that the structure preserves new information about how the dying star expelled its material. Another, more speculative explanation suggests the iron could be part of a curved arc of plasma created when a rocky planet was vaporized during an earlier expansion of the star.

Co author Professor Janet Drew of UCL Physics & Astronomy stressed that key information is still missing. “We definitely need to know more — particularly whether any other chemical elements co-exist with the newly-detected iron, as this would probably tell us the right class of model to pursue. Right now, we are missing this important information.”

What Comes Next for the Research

The team is now preparing a follow up study and plans to gather new data using WEAVE’s LIFU at higher spectral resolution. These observations should help clarify how the iron bar formed and whether other elements are present alongside it.

WEAVE is scheduled to conduct eight major surveys over the next five years, studying objects that range from nearby white dwarfs to extremely distant galaxies. One part of the project, the Stellar, Circumstellar and Interstellar Physics survey led by Professor Drew, is already observing many additional ionised nebulae across the northern Milky Way.

Dr. Wesson noted that similar structures may turn out to be common. “It would be very surprising if the iron bar in the Ring is unique. So hopefully, as we observe and analyze more nebulae created in the same way, we will discover more examples of this phenomenon, which will help us to understand where the iron comes from.”

Professor Scott Trager, WEAVE Project Scientist at the University of Groningen, added: “The discovery of this fascinating, previously unknown structure in a night-sky jewel, beloved by sky watchers across the Northern Hemisphere, demonstrates the amazing capabilities of WEAVE. We look forward to many more discoveries from this new instrument.”

Notes

1. 1 See e.g. https://www.ucl.ac.uk/news/2023/aug/second-james-webb-image-ring-nebula-hints-dying-stars-companion https://www.cardiff.ac.uk/news/view/2739414-astronomers-spy-structures-that-no-previous-telescope-could-detect-in-new-images-of-dying-star
2. The Ring Nebula is also known as M 57 — the 57th listing in Messier’s catalogue of ‘Nebulae and Star Clusters’. John L E Dreyer also included it in his New General Catalogue, first published in 1888 by the Royal Astronomical Society, where it appears as NGC 6720.
3. Once a star like the Sun runs out of hydrogen fuel, it expands to become an extreme red giant and sheds its outer layers, which then coast out to form a glowing shell. A shell created in this way is known in astronomy as a planetary nebula. The leftover stellar core becomes a white dwarf, which, though no longer burning any fuel, continues to shine as it slowly cools over billions of years. The Ring Nebula is a planetary nebula located 2,600 light years (or 787 parsec) away, that is thought to have formed about 4,000 years ago. Planetary nebula ejection returns matter forged in a star to interstellar space and is the source of much of the Universe’s carbon and nitrogen — key building blocks of life on Earth. Stars more than about eight times the mass of the Sun age differently, ending life abruptly in a powerful explosion called a supernova as they collapse to form a black hole or neutron star.
4. Funding for the WEAVE facility has been provided by UKRI STFC, the University of Oxford, NOVA, NWO, Instituto de Astrofísica de Canarias (IAC), the Isaac Newton Group partners (STFC, NWO, and Spain, led by the IAC), INAF, CNRS-INSU, the Observatoire de Paris, Région Île-de-France, CONACYT through INAOE, the Ministry of Education, Science and Sports of the Republic of Lithuania, Konkoly Observatory (CSFK), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Lund University, the Leibniz Institute for Astrophysics Potsdam (AIP), the Swedish Research Council, the European Commission, and the University of Pennsylvania. The WEAVE Survey Consortium consists of the ING, its three partners, represented by UKRI STFC, NWO, and the IAC, NOVA, INAF, GEPI, INAOE, Vilnius University, FTMC — Center for Physical Sciences and Technology (Vilnius), and individual WEAVE Participants. The WEAVE website can be found at https://weave-project.atlassian.net/wiki/display/WEAVE and the full list of granting agencies and grants supporting WEAVE can be found at https://weave-project.atlassian.net/wiki/display/WEAVE/WEAVE+Acknowledgements.
5. The William Herschel Telescope is the leading telescope of the Isaac Newton Group (ING), which in turn is part of the Roque de los Muchachos Observatory on La Palma, in the Canary Islands. The ING is jointly operated by the United Kingdom (STFC-UKRI), the Netherlands (NWO) and Spain (IAC, funded by the Spanish Ministry of Science, Innovation and Universities).

Interactions between phages — viruses that infect bacteria — and their hosts play an integral role in microbial ecosystems. Often described as being in an evolutionary “arms race,” bacteria can evolve defenses against phages, while phages develop new ways to thwart defenses. While virus-bacteria interactions have been studied extensively on Earth, microgravity conditions alter bacterial physiology and the physics of virus-bacteria collisions, disrupting typical interactions.

However, few studies have explored the specifics of how phage-bacteria dynamics differ in microgravity. To address that gap, Huss and colleagues compared two sets of bacterial E. coli samples infected with a phage known as T7 — one set incubated on Earth and the other aboard the International Space Station.

Analysis of the space-station samples showed that, after an initial delay, the T7 phage successfully infected the E. coli. However, whole-genome sequencing revealed marked differences in both bacterial and viral genetic mutations between the Earth samples versus the microgravity samples.

The space-station phages gradually accumulated specific mutations that could boost phage infectivity or their ability to bind receptors on bacterial cells. Meanwhile, the space-station E. coli accumulated mutations that could protect against phages and enhance survival success in near-weightless conditions.

The researchers then applied a high-throughput technique known as deep mutational scanning to more closely examine changes in the T7 receptor binding protein, which plays a key role in infection, revealing further significant differences between microgravity versus Earth conditions. Additional experiments on Earth linked these microgravity-associated changes in the receptor binding protein to increased activity against E. coli strains that cause urinary tract infections in humans and are normally resistant to T7.

Overall, this study highlights the potential for phage research aboard the ISS to reveal new insights into microbial adaption, with potential relevance to both space exploration and human health.

The authors add, “Space fundamentally changes how phages and bacteria interact: infection is slowed, and both organisms evolve along a different trajectory than they do on Earth. By studying those space-driven adaptations, we identified new biological insights that allowed us to engineer phages with far superior activity against drug-resistant pathogens back on Earth.”

In your coverage, please use this URL to provide access to the freely available paper in PLOS Biology: https://plos.io/4q4S9AO

Citation: Huss P, Chitboonthavisuk C, Meger A, Nishikawa K, Oates RP, Mills H, et al. (2026) Microgravity reshapes bacteriophage-host coevolution aboard the International Space Station. PLoS Biol 24(1): e3003568. https://doi.org/10.1371/journal.pbio.3003568

Author countries: United StatesFunding: This work was supported by the Defense Threat Reduction Agency (https://www.dtra.mil/) (Grant HDTRA1-16-1-0049) to S.R. C.C. was supported by a graduate training scholarship from the Anandamahidol Foundation (Thailand). The sponsors or funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Despite its potential, thyme extract has practical drawbacks that limit how it can be used. It evaporates quickly (a waste of thyme!), which makes storage and precise delivery difficult. In larger amounts, it can also irritate the body, sometimes leading to skin rashes or digestive discomfort.

A New Way to Preserve and Control Thyme Extract

Scientists have identified a way to solve both of these problems by sealing extremely small droplets of thyme extract inside another liquid. This approach allows the extract to be delivered in very small doses while preventing evaporation. Researchers from Tomsk Polytechnic University and Surgut State University in Russia developed this method for creating encapsulated nanodoses of thyme. Their findings were published in Physics of Fluids, by AIP Publishing.

How the Encapsulation Process Works

The process relies on carefully controlled streams of thyme extract, gelatin, sodium alginate — a commonly used thickening agent in the food industry — and oil. First, the researchers combined thyme extract with gelatin and pushed this mixture through a tiny chip at the same time as a stream of sodium alginate. Inside the chip, the two liquids flowed together while remaining clearly separated. A stream of oil introduced from a perpendicular direction then broke the combined flow into extremely small droplets, each one fully encapsulated.

Why Precision Nanodosing Matters

The most important outcome of this research is not the specific amount of thyme extract used, but the proof that precise and consistent nanodosing is achievable. Before this approach can be applied in medicine, additional work will be needed to package these nanodoses into oral capsules suitable for pharmaceutical use.

“The system tends to be self-regulating in order to deliver a relatively consistent dose, which is valuable for drug delivery,” said author Maxim Piskunov. “At the same time, changing and adjusting the diameter of the microdroplets containing a biologically active substance nanodose is only possible by varying the oil phase flow rate.”

Applications Beyond Medicine

The researchers emphasize that the technique is not limited to thyme extract alone. It could also be used for other substances and has potential applications outside pharmaceuticals, including the food industry. Piskunov added that combining this method with machine vision and artificial intelligence could allow real-time monitoring and control of nanodosing.

“We believe that this method can be used to encapsulate various aqueous extracts,” said Piskunov. “From our study, no significant limitations have been identified. Moreover, we are currently working on encapsulating a water-alcohol extract with a much higher concentration of biologically active substances.”

The research, publishedin the leading cancer journal Annals of Oncology, goes beyond broad comparisons to show which specific policy changes or system improvements could have the greatest impact on cancer survival in each nation. The team has also created an online tool that allows users to select a country and see how factors such as national wealth, access to radiotherapy, and universal health coverage relate to cancer outcomes.

Turning Global Data Into Practical Insights

Dr. Edward Christopher Dee, a resident physician in radiation oncology at Memorial Sloan Kettering (MSK) Cancer Center in New York, USA, and a co-leader of the study, highlighted why the work matters. “Global cancer outcomes vary greatly, largely due to differences in national health systems. We wanted to create an actionable, data-driven framework that helps countries identify their most impactful policy levers to reduce cancer mortality and close equity gaps.”

He noted that several factors consistently stood out. “We found that access to radiotherapy, universal health coverage and economic strength were often important levers being associated with better national cancer outcomes. However, other key factors were relevant as well.”

Analyzing Cancer and Health System Data From 185 Countries

To reach these conclusions, Dr. Dee and his colleagues used machine learning to examine cancer incidence and death data from the Global Cancer Observatory (GLOBOCAN 2022), covering 185 countries. They combined this information with health system data gathered from the World Health Organization, the World Bank, United Nations agencies, and the Directory of Radiotherapy Centres.

The dataset included health spending as a percentage of GDP, GDP per capita, the number of physicians, nurses, midwives, and surgical workers per 1000 people, levels of universal health coverage, access to pathology services, a human development index, the number of radiotherapy centers per 1000 people, a gender inequality index, and the share of healthcare costs paid directly by patients.

Building the Machine Learning Model

The machine learning model was developed by Mr, Milit Patel, the study’s first author. He is a researcher in biochemistry, statistics and data science, healthcare reform and innovation at the University of Texas at Austin, USA, and at MSK.

Mr, Patel explained the reasoning behind this approach. “We chose to use machine learning models because they allow us to generate estimates – and related predictions – specific to each country. We are, of course, aware of the limitations of population level data but hope these findings can guide cancer system planning globally.”

Measuring Cancer Care Effectiveness

The model calculates mortality-to-incidence ratios (MIR), which represent the share of cancer cases that result in death and serve as an indicator of how effective cancer care is in a given country. To show how individual factors influence these estimates, the researchers used a method that explains predictions by measuring each variable’s contribution, known as SHAP (Shapley Additive exPlanations).

According to Mr. Patel, the goal was to move from description to action. “Beyond simply describing disparities, our approach provides actionable, data-driven roadmaps for policymakers, showing precisely which health system investments are associated with the greatest impact for each country. As the global cancer burden grows, these insights can help nations prioritize resources and close survival gaps in the most equitable and effective way possible. International organizations, healthcare providers, and advocates may also use the web-based tool to highlight areas for investment, especially in resource-limited settings.”

Country Examples Show Different Priorities

The results reveal that the most influential factors vary widely by country. In Brazil, the model indicates that universal health coverage (UHC) has the strongest positive association with improved mortality-to-incidence ratios. Other factors, such as pathology services and the number of nurses and midwives per 1000 people, appear to play a smaller role at present. The researchers suggest this means Brazil could see the greatest gains by prioritizing UHC.

In Poland, the availability of radiotherapy services, GDP per capita, and the UHC index show the largest impact on cancer outcomes. This pattern suggests that recent efforts to expand health insurance and access to care have produced stronger improvements than general health spending, which appears to have a more limited effect.

Japan, the USA, and the UK show a broader pattern, with nearly all health system factors linked to better cancer outcomes. In Japan, the density of radiotherapy centers stands out most strongly, while in the USA and the UK, GDP per capita has the greatest influence. These findings point to where policymakers in each country may achieve the biggest gains.

China presents a more mixed picture. Higher GDP per capita, broader UHC, and greater access to radiotherapy centers contribute most to improved cancer outcomes. By contrast, out-of-pocket spending, the size of the surgical workforce per 1000 people, and health spending as a percentage of GDP currently explain less of the variation in outcomes.

The researchers write about China: “High direct costs for patients remain a critical barrier to optimal cancer outcomes, even amidst national improvements in health financing and access. These findings underscore that while China’s rapid health system development is yielding important gains in cancer control, disparities in financial protection and coverage persist, warranting intensified policy focus on reducing out-of-pocket expenditures and further strengthening UHC implementation to maximize health system impact.”

How to Read the Green and Red Bars

Mr, Patel also explained the meaning of the green and red bars shown in the country-specific graphs. “The green bars represent factors that currently appear most strongly and positively associated with improved cancer outcomes in a given country. These are areas where continued or increased investment is most likely to result in meaningful impact.”

He stressed that red bars should not be misunderstood. “However, the red bars do not indicate that these areas are unimportant or should be neglected. Rather, they reflect domains that, according to the model and current data, are less likely to explain the largest differences in outcomes right now. This may be due to already strong performance in these aspects, limitations of the available data, or other context-specific factors.”

He added an important caution. “Importantly, seeing a ‘red’ bar should never be interpreted as a reason to stop efforts to strengthen that pillar of cancer care – improvement in those areas can still be valuable for a country’s overall health system. Our results simply suggest that, if the goal is to maximize improvement in cancer outcomes as defined by the model, focusing first on the strongest positive (green) drivers may be the most impactful strategy.”

Strengths, Limits, and What Comes Next

The study’s strengths include its coverage of nearly all countries, use of current global health data, country-specific policy guidance rather than simple global averages, and the use of more transparent AI models. The researchers also acknowledge key limitations. The analysis relies on national-level data rather than individual patient records, data quality varies widely, especially in many low-income countries, and national trends can hide disparities within countries. In addition, the study cannot prove that focusing on a specific factor will cause better cancer outcomes, only that such efforts are associated with improved results.

Even with these limits, the findings offer a useful way to prioritize action. Dr. Dee concluded: “As the global cancer burden grows, this model helps countries maximize impact with limited resources. It turns complex data into understandable, actionable advice for policymakers, making precision public health possible.”