A meteor hit Oklahoma 100 million years later than scientists thought

 Researchers at The University of Texas at Austin have revised a key piece of Oklahoma's geologic history, with possible implications for how scientists interpret major events in the history of life on Earth.

Beneath the town of Ames, Oklahoma, lies a meteor impact structure that stretches for miles underground. Layers of sediment now cover the crater, but it remains significant both scientifically and economically. The Ames impact structure is also a major producer of oil and gas.

A Crater Long Linked to an Ancient Meteor Event

For years, the Ames crater was thought to belong to a cluster of major meteor impacts across North America dating to roughly 467.5 million years ago. That period is known as the Ordovician Meteor Event.

Because so many impact structures appear to date from around the same time, some researchers have proposed that Earth may once have been surrounded by a Saturn-like ring of asteroid debris during the Middle Ordovician.

New work from UT researchers now shows that the Ames impact does not belong to that episode.

By dating zircon crystals taken from granite altered by the impact, the team determined that the meteorite struck about 370 million years ago during the Late Devonian. That makes the crater nearly 100 million years younger than previously believed.

"No matter what technique we used, it was coming back to this younger signal," said lead author Elizabeth Catlos, associate professor at UT's Department of Earth and Planetary Sciences.

The research was published in July in Meteoritics & Planetary Science.

Why the Earlier Date Was Misleading

Before this study, the Ames impact had only been dated using biological evidence. Researchers had found teeth from an ancient eel-like animal called a conodont preserved in the rock. Those fossils came from organisms that lived during the older Ordovician period.

But Catlos said the teeth were probably already millions of years old by the time the asteroid struck. The impact likely churned up older material and mixed the fossils into the rocks while still preserving them.

The zircon dating provides a very different timeline. It shows that the Ames crater could not have formed during the Ordovician Meteor Event.

Instead, its new age places it close to the Frasnian-Famennian mass extinction event, which occurred about 372 million years ago and wiped out a large proportion of marine life on Earth.

Tiny Zircon Crystals Preserve the Impact

Danny Stockli, dean of the Jackson School of Geosciences and a co-author of the study, said zircon U-Pb dating offers one of the most accurate ways to determine when events occurred deep in Earth's past.

Zircon crystals can also preserve microscopic structures created by the intense pressures generated during an impact.

"These small crystals allow us to go back in time and learn about the major changes to Earth's ancient landscapes," Stockli said. "It would be great to do this for more of the meteor impact sites across the continent so we could get a more accurate timeline for these major events."

To confirm that the zircons had actually been affected by the meteor strike, the team worked with NASA to image the crystals using cathodoluminescence and electron backscatter diffraction.

When zircon experiences the extreme conditions of an impact, it recrystallizes in a distinctive way. Those changes can be detected with these imaging techniques, allowing researchers to verify that the crystals recorded the collision itself.

A New Piece of a Mass Extinction Puzzle

According to Catlos, establishing more precise dates for mass extinctions and other major events is essential for understanding how Earth has changed over time.

One key question is whether extinction events were triggered primarily by forces from space, such as meteor impacts, or by processes within Earth, including episodes of massive volcanic activity.

"With this research, we're basically taking a major pawn out of the Ordovician Meteor Event and dumping it into the Frasnian-Famennian event, and saying, 'This is where this impact belongs,'" she said.

The project was initiated by former Jackson School of Geosciences graduate student Andrew Parisi, who graduated in 2018 and has since passed away. Parisi traveled to Oklahoma to obtain the Ames rock core from the Oklahoma Geological Survey, extracted zircon crystals from the material, and helped determine their ages.

Co-author Michael Brookfield, an affiliated researcher at the school, also passed away before the paper was published.

Research Professor Sean Gulick and Professor Emeritus Mark Cloos at the Jackson School also contributed to the research.

Source: ScienceDaily

Easing constipation: A 20-minute walk can get your gut moving almost immediately

 Constipation is one of the most common digestive problems, affecting people across age groups and backgrounds. Beyond causing bloating, straining, and infrequent bowel movements, it can also interfere with daily life by increasing stress, reducing productivity, and lowering overall quality of life. When constipation becomes persistent, it may also contribute to complications such as hemorrhoids, cardiovascular strain, and an increased risk of colorectal problems.

Despite how widespread it is, constipation is often ignored or left untreated until symptoms become difficult to manage. That makes it important to better understand both what causes sluggish bowel function and which strategies can help restore normal digestion.

Why Walking May Help the Gut

Physical activity is one of the simplest approaches commonly recommended for constipation. People who are more active generally tend to have healthier bowel function, while prolonged inactivity is often associated with slower digestion.

Exactly why movement helps, however, is not fully understood. Much of the previous research has examined the effects of regular exercise over longer periods. Scientists know much less about what happens inside the digestive system immediately after a person starts moving.

Understanding those rapid changes could help explain why even a relatively short walk may help stimulate bowel function.

Researchers from Fujita Health University set out to investigate how quickly physical activity can influence gut motility in healthy adults. In their study, published in Scientific Reports, the team used bowel sounds (BS) as a non-invasive way to monitor intestinal activity.

Bowel sounds are produced as gas and fluid move through the intestines. Because those movements are related to the contractions that propel digestive contents through the gut, the sounds can provide clues about gut motility. By recording them before and after exercise, the researchers were able to examine how rapidly the digestive system responded to walking.

What Happened After a 20 Minute Walk

The study included 21 healthy young adults. At the beginning of the experiment, each participant lay quietly while the researchers recorded one minute of baseline BS using an electronic stethoscope and advanced signal-processing software.

The participants then walked on a treadmill for 20 minutes at a comfortable, self-selected pace. After the walk, they returned to a lying position while the researchers recorded BS at several points during the following 15 minutes.

Gut motility was evaluated using three measurements. These included the Sound Index (SI), which measures the total amplitude of sound activity; the percentage of recording time during which BS could be detected; and the number of separate BS events occurring each minute.

The response appeared quickly.

Within one to two minutes after participants finished walking, all three measures had risen significantly compared with their resting levels. The amplitude of the bowel sounds nearly doubled, the sounds were present during a much larger share of the recordings, and the number of individual sounds per minute also increased.

The effect did not last long. The increases diminished within two to three minutes. Still, the speed of the response showed that even light activity can produce an immediate and measurable increase in gut motility.

A Possible Explanation for Walking and Constipation Relief

The findings may help clarify why walking is so often recommended for people dealing with constipation.

Professor Yohei Otaka, senior author of the study, shares, "Walking can serve as an effective, immediate tool for stimulating bowel function. The findings also point to potential underlying mechanisms, such as changes in autonomic nervous system activity or reflexes triggered by the body's natural oscillations during movement."

The autonomic nervous system helps regulate many automatic functions in the body, including digestion. The physical motion created while walking could also contribute by triggering reflexes that encourage the intestines to become more active.

The research team also included Professor Shigeo Tanabe (Graduate School of Health Sciences, Fujita Health University) and Kento Katagiri (Department of Rehabilitation Medicine, School of Medicine, Fujita Health University), who contributed to study design, analysis, and manuscript preparation.

Bowel Sounds Could Offer a New Research Tool

Beyond the effects of walking itself, the findings suggest that BS analysis could become a useful non-invasive method for studying gastrointestinal function and constipation.

Because bowel sounds can be monitored without more invasive procedures, researchers may be able to use the technique to track short term changes in intestinal movement and better understand how different behaviors or treatments affect the digestive system.

Source: ScienceDaily

The “glue” holding your cells together has a surprising second job

 A protein best known for helping cells and tissues stay connected has another unexpected role. Researchers have found that it also helps epithelial cells, which form continuous sealed layers throughout the body, engulf nearby dead cells.

The discovery could have implications for chronic inflammation. Debris from dying cells is a major contributor to inflammatory responses, so understanding how tissues remove that material may reveal new clues about what happens when the cleanup process fails.

The study, published in Nature Communications, focuses on the E-cadherin complex. This molecular system includes E-cadherin along with three additional proteins. Together, they connect epithelial cells lining areas such as the skin, gut and airways, giving tissues the structural strength they need to remain intact. In these tissues, each cell connects to E-cadherin molecules on neighboring cells.

Cellular Glue Takes on a Cleanup Role

A team led by Verena Ruprecht examined epithelial tissues in living zebrafish and mouse embryos. They found that the same molecular machinery also gathers at the exact location where a dying cell comes into contact with the tissue.

The researchers wanted to know whether E-cadherin and its partners were attaching to the dying cell in the same way they normally attach neighboring epithelial cells. To test that possibility, they carried out two experiments.

First, they presented the tissue with dying cells that had been stripped of E-cadherin. The epithelial tissue removed those cells just as effectively as it removed normal dying cells. Next, the team introduced fat droplets that contained no protein at all but carried a signal normally displayed on the surface of dying cells. The epithelial cells engulfed those droplets as well.

"We were intrigued to find out that epithelial cells repurpose their molecular adhesion machinery -- the 'glue' that normally holds them together -- to engulf dying cells," says ICREA Research Professor Verena Ruprecht, senior author of the study.

How Cells Eat Without Breaking the Barrier

Engulfing something roughly the size of another cell presents a difficult mechanical problem. Epithelial cells are tightly packed into barriers that often need to remain sealed, even while individual cells reshape themselves to remove debris.

Live imaging revealed how they accomplish this. The upper and lower surfaces of the same epithelial cell can behave differently from one another. The lower surface stretches and bends around the dead cell, while the opposite side remains relatively unchanged.

That upper surface, which may face the outside environment or an open space such as the inside of a lumen, continues maintaining the tissue barrier. Measurements taken before, during and after engulfment showed that the area of the upper surface changed very little. By contrast, the lower surface underwent substantial deformation during the 'eating' process.

Ruprecht compares the behavior to a row of dancers standing with their arms linked. Their upper bodies remain steady while their feet perform increasingly complicated movements when a dying cell appears. "It's the same dancer with a different choreography," she says.

A Molecular Rope and Brake

The researchers also examined the mechanics that allow the cells to perform this cleanup.

One protein in the E-cadherin complex acted much like a rope. It connected the molecular assembly to the cell's internal skeleton, allowing force to be transmitted across the surface of the material being engulfed. When cells lacked this tethering protein, or lacked the specific region that attaches it to the skeleton, they could no longer swallow dead cells.

Another component behaved more like a brake on the cell's contractile machinery. Surprisingly, removing this brake did not make the cleanup process more effective. Instead, the cell became too stiff and lost its ability to properly remove dying cells.

The Same Mechanism Appears in Mammals

The team next investigated whether the process extends beyond zebrafish.

In early mouse embryos, blocking E-cadherin caused dying cells to remain uncleared. This matched the results seen in zebrafish and suggests that the mechanism is shared among vertebrates.

The new work builds on earlier research from Ruprecht showing that embryos can use epithelial tissues to cooperatively remove dying cells. That behavior represents a form of early innate immune defense.

Embryos are particularly useful for studying these events because they are transparent. Researchers can observe living cells and tissues directly at a level of detail that cannot currently be achieved inside the human body.

Source: ScienceDaily

One immune switch may help drive aging across the body

 Aging happens at different speeds from one person to another, but it eventually affects everyone. New research from Stanford Medicine, conducted in mice and human cells, points to a particular failure in the immune system that may help explain why.

The researchers found that tissue-resident macrophages, a type of immune cell that lives permanently within organs, become less able with age to dispose of another class of immune cells. That decline appears to contribute to aging throughout the body.

When the scientists blocked a single receptor on these macrophages, multiple organs in mice retained more youthful characteristics. The effects were seen in the brain, heart, skeletal and heart muscle, liver, spleen, bone marrow, kidney, and colon. The receptor normally responds to a hormone involved in inflammation and pain in both mice and humans.

Disabling the receptor specifically in tissue-resident macrophages also protected mice from several problems associated with chronic inflammation and aging, including frailty, excess fat accumulation and heart trouble. Cognitive decline was substantially reduced as well, according to Katrin Andreasson, MD, the Edward F. and Irene Thiel Pimley Professor in Neurology and Neurological Sciences.

"We've been trying to figure out why we age," Andreasson said. "Now we know at least one big reason for it."

The findings are described in a paper published in Science. Andreasson is the senior author, and Jessy Tan, PhD, an instructor in neurology, is the lead author.

The results provide new insight into the important role that chronic, body-wide inflammation plays in aging and its associated health problems. They also point toward a potential drug strategy that could slow age-related deterioration in organs and possibly extend the number of years people remain healthy.

How the Immune System Clears Aging Cells

Neutrophils are the most abundant white blood cells in the immune system and serve as some of the body's most important first responders. They are produced in bone marrow and then enter the bloodstream, where they patrol for bacterial, viral, and fungal threats.

When neutrophils encounter pathogens, they can release toxic substances and even destroy themselves, spilling long strands of biological material that form web-like traps around invading microbes.

These cells do not live for long. A neutrophil may survive for as much as 24 hours, although 12 hours is more typical. Roughly 90% of circulating neutrophils eventually arrive in the liver, spleen, and bone marrow, where other immune cells remove them.

That disposal process is especially important as the body grows older. In aging animals, most neutrophils that never encounter a pathogen quickly enter senescence, a dysfunctional state in which they can release harmful chemicals that damage nearby cells and promote inflammation.

Neutrophil numbers increase with age, and a growing proportion of them become senescent.

"Senescent neutrophils are killing our tissues," Andreasson said. "Clearance of these cells is essential for preventing chronic inflammation."

The Body's Cellular Garbage Collectors

Macrophages are responsible for much of that cleanup. These versatile immune cells fight pathogens, coordinate responses from other cells and release growth factors that help damaged tissues repair themselves.

They also remove dead and dysfunctional cells.

"They're the body's garbage collection crew. A lot of that garbage is defunct cells." Andreasson said.

A large share of that cellular waste consists of neutrophils, with roughly 100 billion of them needing to be cleared every day.

There are several kinds of macrophages. Tissue resident macrophages are unusually long-lived cells that settle into organs during fetal development. Once established, they remain in those organs throughout life and adapt to perform specialized jobs in each location.

One of their most important responsibilities is swallowing senescent cells. The new findings show that neutrophils are particularly significant targets. About 100 billion neutrophils are produced each day, and they begin showing signs of senescence only 8 to 12 hours after entering the bloodstream. (Neutrophils that haven't arrived at senescence yet but have lived long enough and seen enough to put out "kill me now" flags of surrender on their cell surfaces are fair game.)

The problem is that tissue-resident macrophages themselves deteriorate with age. Andreasson and her colleagues reported in a 2021 Nature study that these long-lived immune cells become increasingly vulnerable to inflammation as animals grow older. They can then contribute to that inflammation themselves.

An Inflammatory Signal Grows Stronger With Age

One important part of this process involves prostaglandins, hormones produced by immune cells. One of the five types, called PGE2, can affect cells in different ways depending on which receptors are present on their surfaces.

One receptor for PGE2, known as EP2, strongly promotes inflammation. Tissue-resident macrophages contain large amounts of EP2.

PGE2 production rises in response to infection, injury and toxic substances, including compounds produced as the body ages. The researchers' earlier work showed that PGE2 levels increase substantially over time. At the same time, tissue resident macrophages develop higher concentrations of EP2.

Together, those changes create a harmful feedback process. Increasing PGE2 activity repeatedly stimulates EP2 receptors on tissue-resident macrophages. The new study found that this stimulation weakens the macrophages' ability to engulf neutrophils.

As a result, senescent neutrophils begin accumulating in the bloodstream and tissues.

Previous research from Andreasson's group also showed that the energy metabolism of tissue resident macrophages gradually deteriorates with age.

"Once that starts, there's a steady decline in a macrophage's performance," she said.

The new work suggests that EP2 is critical to that decline.

"We've shown that when tissue-resident macrophages don't have EP2 on their surfaces anymore or when that receptor is plugged up by a drug, this decline doesn't happen."

Blocking One Receptor Protects Multiple Organs

To investigate the receptor's role more closely, Andreasson's laboratory engineered mice whose EP2 gene could be deleted at a time chosen by the scientists, specifically in tissue-resident macrophages.

Removing EP2 restored the macrophages' ability to dispose of neutrophils, reversing the disruption caused by PGE2.

Source: ScienceDaily

Scientists say house cats could help unlock better cancer treatments for humans

 Scientists have taken a major step toward understanding cancer in cats, opening what researchers once described as a genetic "black box."

In a large international study published in Science, researchers genetically analyzed cat cancers on a scale that had not been attempted before. The work could improve cancer care for cats while also helping scientists better understand how some cancers develop in humans and other animals.

The researchers also created a freely available resource that other scientists can use to study the genetics of feline cancer.

Cancer is one of the leading causes of illness and death in cats, yet scientists have historically known far less about the genetic changes behind feline tumors than they do about cancers in humans or dogs.

Dr. Geoffrey Wood, a University of Guelph pathobiology professor and co-senior author of the study, said that gap has now begun to close.

"Despite domestic cats being common pets, there was very little known about the genetics of cancer in these animals," Wood says, "until now."

Cat and Human Cancers Share Key Genetic Changes

Researchers examined tumor samples from almost 500 domestic cats in five countries, searching for mutations and other genetic changes that help cancers form and grow.

Many cancers are driven by changes in certain genes that normally help control how cells grow, divide, repair damage, or die. When these genes are altered, cells can begin multiplying uncontrollably. Scientists often refer to genes that contribute directly to tumor growth as cancer driver genes.

The team found that many of the driver genes involved in cat cancers were also familiar from human and dog cancers.

One of the clearest examples appeared in aggressive mammary cancers, which arise in breast tissue.

The most common driver gene found in cat mammary tumors was FBXW7. More than 50 percent of the tumors examined carried a mutation in this gene.

FBXW7 normally helps regulate proteins involved in cell growth and division. When the gene is damaged, some of those growth promoting proteins can accumulate, potentially helping cancer cells survive and spread.

In humans, mutations in the FBXW7 gene in breast cancer are associated with worse prognosis - paralleling the change seen in cats.

Researchers also identified similarities between cat and human cancers affecting the blood, bones, lungs, skin, gastrointestinal system and central nervous system.

Shared Environments May Offer Cancer Clues

The similarities may be especially useful because domestic cats often live in the same environments as people.

Cats can encounter some of the same environmental factors as their owners, including household chemicals, air pollutants, smoke and other exposures that may influence cancer risk. Studying naturally occurring cancer in pets could therefore help researchers investigate how genetics and the surrounding environment interact.

"This study can help us understand more about why cancer develops in cats and humans, how the world around us influences cancer risk, and possibly find new ways to prevent and treat it," says Wood.

The genetic findings could also have implications for treatment.

Researchers found that certain chemotherapy drugs were more effective against cat mammary tumors carrying the mutated FBXW7 gene.

The result was observed only in tissue samples, so it does not yet show that the same approach will work in living cats or people. Still, the finding suggests that genetic information could eventually help doctors and veterinarians identify treatments that work better for particular tumors.

This type of approach is known as precision oncology. Instead of treating every cancer of the same general type in exactly the same way, precision oncology uses the molecular and genetic features of an individual tumor to help guide therapy.

"Having access to such a large set of donated tissues allowed us to assess drug responses across tumor types," says Dr. Sven Rottenberg, co-senior author at the University of Bern, "in a way that hasn't been possible at this scale before."

Bailey Francis, co-first author at the Wellcome Sanger Institute, said the findings could also have implications for dogs.

"When knowledge and data flows between different disciplines, we can all benefit."

Using Cat Cancer Research to Help Pets and People

The project brought together researchers from the Wellcome Sanger Institute, U of G's Ontario Veterinary College, the University of Bern and other institutions.

Rather than collecting all new samples, the team sequenced DNA from tissues that veterinarians had already obtained for diagnostic purposes.

That allowed scientists to study naturally occurring cancers from a large number of cats and compare the genetic patterns among different tumor types.

The findings also support a broader research strategy known as One Medicine.

The One Medicine approach emphasizes that human and veterinary medicine can inform one another. Cancer treatments developed for humans could potentially be evaluated in cats with naturally occurring tumors, while discoveries made during feline cancer studies and clinical trials could provide clues that help shape future human research.

That two way exchange is especially valuable because pets naturally develop many of the same diseases as people while sharing many aspects of the same environment.

Researchers hope the new genetic database will ultimately help bring more personalized cancer care to cats.

Dr. Louise Van Der Weyden, senior author at the Wellcome Sanger Institute, said the study provides a foundation for the next stage of feline cancer research.

"We can now begin to take the next steps forwards towards precision feline oncology, to catch up with the diagnostic and therapeutic options that are available for dogs with cancer, and ultimately one day, humans."

The research was funded in part by EveryCat Health Foundation, the CVS Group, Wellcome, the Natural Sciences and Engineering Research Council of Canada and the Swiss National Science Foundation.

Source: ScienceDaily

Stopping Ozempic may raise heart attack and stroke risk

 GLP-1 drugs such as semaglutide (Ozempic and Wegovy) and tirzepatide (Mounjaro and Zepbound) have surged in popularity for treating diabetes and helping people lose weight. About one in eight U.S. adults now use these medications, which are also known to provide cardiovascular benefits. But new research suggests that those heart benefits may fade quickly when treatment is stopped.

Researchers at Washington University School of Medicine in St. Louis tracked more than 333,000 U.S. veterans with type 2 diabetes for three years. They found that interrupting or stopping GLP-1 treatment for as little as six months was associated with a meaningful increase in the risk of major cardiovascular events compared with remaining on the medication.

The longer patients stayed off treatment, the greater the increase in risk. After two years without GLP-1 therapy, the risk of heart attack, stroke and death was up to 22% higher than among people who continued treatment, largely wiping out the cardiovascular protection gained while taking the drugs.

The findings, published in BMJ Medicine, suggest that stopping GLP-1 medications may have consequences that extend well beyond weight regain. They also point to the importance of uninterrupted treatment for maintaining heart protection.

"There is enormous exuberance about starting GLP-1 drugs, but not nearly enough attention to what happens when people stop," said senior author Ziyad Al-Aly, MD, a WashU Medicine clinical epidemiologist and chief of the Research and Development Service at the VA Saint Louis Health Care System. "Many quit after a few months because of cost, side effects or shortages. When they stop, it's not just weight that comes back; they experience a resurgence in inflammation, blood pressure, and cholesterol. Weight regain is visible; the metabolic reversal is not."

"Our data suggest this metabolic whiplash is detrimental to heart health," Al-Aly added. "Restarting the medication helped restore some protection, but only partially, showing that discontinuation leaves a lasting scar."

Heart protection depends on continued GLP-1 use

GLP-1 medications include the semaglutide drugs Ozempic and Wegovy and the tirzepatide drugs Mounjaro and Zepbound. After observing that about half of users stop taking GLP-1 drugs not long after beginning treatment, Al-Aly set out to examine what happens to cardiovascular health after therapy is discontinued.

The study focused on major adverse cardiovascular events, including heart attack, stroke and death. Researchers analyzed data from 333,687 veterans with type 2 diabetes. Of those, 132,551 had been prescribed GLP-1 drugs, while 201,136 had been prescribed sulfonylureas, another class of diabetes medications.

Sulfonylureas include glipizide (Glucotrol), glimepiride (Amaryl), and glyburide (Diabeta and others). Participants were followed for up to three years.

Researchers reassessed GLP-1 treatment status every six months. During the study, 26% of GLP-1 users stopped taking the medication altogether. Another roughly 23% experienced a treatment gap lasting at least six months before eventually restarting therapy.

Continuous treatment produced the greatest benefit

The clearest cardiovascular benefit appeared among people who remained on GLP-1 medications throughout the full three-year study period.

Compared with participants taking sulfonylureas, those who consistently stayed on GLP-1 therapy had an 18% lower risk of major cardiovascular events. That translated to about four fewer major cardiovascular events for every 100 people over three years.

Participants who stayed on GLP-1 treatment for two years or two-and-a-half years before stopping for the rest of the study also saw meaningful reductions in risk, at 7% and 15%, respectively.

By contrast, people who discontinued GLP-1 therapy before reaching 18 months showed no significant reduction in cardiovascular risk compared with those taking sulfonylureas by the end of the study.

Treatment gaps weakened heart protection

Interrupting treatment and then restarting it also appeared to reduce the cardiovascular benefit.

People who remained on GLP-1 drugs continuously for three years had an 18% reduction in risk, while those who stopped temporarily and later resumed treatment saw an average reduction of 12%.

Even a six-month interruption before restarting therapy was enough to weaken the benefit. Compared with continuous use, those treatment gaps were associated with a 4% to 8% increase in cardiovascular risk.

Longer periods off the drugs were linked to even greater losses of protection. People who stopped GLP-1 treatment for one year without restarting had a 14% higher risk of cardiovascular events compared with continuous users. After two years off treatment, that increase reached 22%.

The pattern suggests that cardiovascular benefits accumulated during GLP-1 treatment can be lost relatively quickly once the medication is discontinued.

Restarting may not fully restore lost benefits

The findings reinforce the importance of continuous treatment if patients and clinicians want to preserve the cardiovascular effects of GLP-1 therapy. They also suggest that reducing treatment interruptions could help maximize the drugs' protective effects on the heart.

"Clinicians should treat adherence to GLP-1 treatment as an important outcome in its own right -- not an afterthought," Al-Aly said. "Health systems need plans in place to help people continue their medication indefinitely, recognizing that GLP-1s treat chronic conditions. That includes proactive management of side effects, candid conversations about the long-term nature of treatment, infrastructure to identify and support patients at risk of stopping and addressing the cost barriers that make GLP-1 therapy unsustainable for many."

Al-Aly noted that this is especially important because cardiovascular protection from GLP-1 treatment appears to accumulate gradually but disappear much more quickly.

For study participants, spending only one year off the medication was enough to lose benefits that had taken years of continuous treatment to build. Restarting the drug restored some of that protection, but not all of it.

The research was funded by the United States Department of Veterans Affairs. The funders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication. The contents do not represent the views of the US Department of Veterans Affairs or the US Government.

Source: ScienceDaily

Hidden gut defect that may explain why IBD keeps coming back

 Researchers have identified early molecular warning signs of inflammatory bowel disease that may appear before symptoms and remain active even when patients seem to be doing well.

The study, led by WEHI in partnership with the Royal Melbourne Hospital, uncovered a hidden defect in intestinal cells that can make them vulnerable to damage. The problem was still detectable in some patients whose disease appeared to be well controlled.

Published in Science, the findings may help explain why people with inflammatory bowel disease can experience sudden flare-ups even after reaching remission.

Key findings

WEHI researchers identified a 'smoldering' molecular defect in gut cells from people with inflammatory bowel disease.

The defect involves abnormal cell death and could be detected even in patients whose disease was under good control.

The work, carried out through a broad collaboration with the Royal Melbourne Hospital, could eventually lead to earlier prediction of flare-ups, more precise monitoring and treatment tailored more closely to individual patients.

A hidden problem in intestinal cells

Inflammatory bowel disease (IBD), which includes conditions such as Crohn's disease and ulcerative colitis, is a chronic condition that affects around 180,000 Australians.

People with IBD can experience serious symptoms including rectal bleeding, abdominal pain, diarrhea, fatigue, and weight loss.

Modern therapies can help many patients achieve remission, but diagnosing and managing IBD remains challenging.

The disease often alternates between periods when symptoms are controlled and sudden flare-ups that can become severe enough to require hospital care.

Study co-author Dr. Andre Samson said the researchers discovered that intestinal cells could remain vulnerable even when patients felt well, and their disease appeared stable.

"Once you've got the diagnosis, IBD doesn't go away. Even if you become symptom-free on the current treatments, we know there's a likelihood you're going to have a flare or relapse," said Dr. Samson.

"What we found in patient samples was that intestinal cells are primed to die. Even in patients with essentially no symptoms, there's still this persistent problem sitting there."

Cell death may help drive IBD

The results challenge the assumption that cell death in IBD is simply damage caused by inflammation. Instead, the researchers say abnormal cell death may be involved in helping drive the disease itself.

The defect was already present during the earliest stages of disease activity, including in patients with clinically mild IBD. Detecting it required detailed molecular analysis.

Study co-author Professor James Murphy said the discovery revealed a 'smoldering' molecular problem and encouraged the researchers to focus more closely on what happens at the beginning of the disease process.

"Most people have been focusing on the major clinical problem, when someone comes to hospital with severe gut inflammation," Prof Murphy, a WEHI deputy director and lab head, said.

"We've gone to the other end of the spectrum and looked at gut tissue that doesn't have clear signs of active disease. What we're finding is this molecular defect happening very early in disease progression - one of the first dominoes to fall."

Human tissue reveals clues to future flare-ups

The research relied entirely on human tissue and patient-derived organoids.

Working with clinicians from the Royal Melbourne Hospital, the team collected around 900 biopsies from 80 people with and without IBD. Researchers used those samples to grow organoids, lab-grown tissues derived from patients, allowing them to investigate the disease directly in human cells.

Study co-author Professor Edwin Hawkins, head of the Colonial Foundation Diagnostics Center where samples were analyzed, said the size and nature of the patient group were important strengths of the research.

"While cell death has been implicated in IBD for a long time, how it arises in humans has remained unclear, probably because most studies rely on mouse models which often do not accurately mimic the human condition," Prof Hawkins, a WEHI lab head, said.

"Our study is based on human tissue and patient biopsies."

Researchers then tracked the patients for more than two years. They found that people showing stronger intestinal cell death signaling were also more likely to experience a relapse.

Toward earlier IBD detection

IBD can behave very differently from one person to another, making it difficult to know who will respond to a particular treatment or who is most likely to relapse.

Study co-author Dr. Jiyi Pang said the newly identified molecular signals could eventually help scientists develop more precise tools for monitoring patients and selecting treatments based on the biology of an individual's disease.

"The causes of IBD are largely unknown and quite variable," Dr. Pang said.

"Using mini-intestinal organoids grown in a dish and by working alongside a diverse team of researchers and clinicians, we uncovered the inflammatory signals responsible for this cell death response."

"We now have the hallmarks of what underlies disease at the molecular level. The question is which of those are therapeutically actionable and whether they might help us to better match treatments to patients, based on how their disease behaves at a molecular level."

More personalized treatment could follow

Study co-author Dr. Aysha Al-Ani cautioned that the findings are unlikely to produce a new diagnostic test or therapy immediately. However, they provide a foundation for future research into better forecasting tools and potential treatments.

"It opens new avenues for different prognostic tools, using more sophisticated and refined methods than are currently used clinically," Dr. Al-Ani said.

"The ethos behind IBD therapy is to reduce the frequency and severity of flares, halting disease progression and improving patients' lives. More sensitive molecular detection may help us keep patients in deep remission for longer and introduce new treatments."

Source: ScienceDaily