Publisher Health

Scientists have created a promising new compound that could mark a major step forward in the global effort to control tuberculosis, the world’s deadliest infectious disease.
A new study in Nature highlights the potential of this compound, called CMX410, which targets a key enzyme in Mycobacterium tuberculosis, the bacterium that causes tuberculosis. The compound has shown success even against drug-resistant strains, a growing global problem that makes treatment more difficult and less effective.
The research was led by James Sacchettini, Ph.D., the Rodger J. Wolfe-Welch Foundation Chair in Science and professor at Texas A&M University, along with Case McNamara, Ph.D., senior director of infectious disease at the Calibr-Skaggs Institute for Innovative Medicines, a division of Scripps Research that develops next-generation therapies.
This discovery emerged from collaborations within the TB Drug Accelerator program, a Gates Foundation-funded initiative that brings together researchers to advance the most promising tuberculosis treatments.
“A lot of people think of tuberculosis as a disease of the past,” Sacchettini said. “But in reality, it remains a major public health issue requiring significant attention, collaboration and innovation to overcome.”
A new approach to an old enemy
The newly identified compound from AgriLife Research and Calibr-Skaggs works by shutting down a vital enzyme, polyketide synthase 13 (Pks13), which the bacterium needs to build its protective cell wall. Without this structure, M. tuberculosis cannot survive or infect the body.

Scientists have long known that Pks13 is an important target for TB drugs, but developing a safe and effective inhibitor has proven difficult. CMX410 succeeds where earlier attempts fell short. Its design makes it extremely specific to its target, resulting in fewer unwanted effects. The compound forms an irreversible bond with a critical site on Pks13, which prevents resistance from developing and keeps the drug focused on its intended target.
To achieve this, researchers used a technique known as click chemistry — a method that links molecules together like puzzle pieces. The approach was pioneered by co-author Barry Sharpless, Ph.D., W.M. Keck Professor of Chemistry at Scripps Research and a two-time Nobel Laureate. His work has opened the door to vast libraries of chemical compounds that can be rapidly tested and refined.
“This technique represents a new tool for drug design,” said McNamara. “We expect to see its uses expand in the coming years to help address public health concerns with a critical need, including tuberculosis.”
Promising early results
The team began by screening a collection of compounds from the Sharpless lab to find those capable of slowing M. tuberculosis growth. After months of optimization, led by co-first authors Baiyuan Yang, Ph.D., and Paridhi Sukheja, Ph.D., CMX410 emerged as the most effective and balanced candidate.
Yang’s team tested more than 300 variations to fine-tune the compound’s power, safety, and selectivity. The final version was tested against 66 different TB strains, including multidrug-resistant samples taken from patients, and proved effective in nearly all cases.

“Identifying this novel target was an exciting moment,” said Sukheja, who led many early studies showing CMX410 could target a previously unexplored gene. “It opened up a completely new path forward, especially against strains that have learned to evade existing treatments.”
The researchers also found that CMX410 can be used safely alongside existing TB drugs, a crucial advantage since treatment typically involves multiple medications taken for several months. In animal testing, no negative side effects were observed even at the highest doses. Because of its precision, the compound is unlikely to disturb healthy bacteria or cause gut imbalance — an issue often linked to traditional antibiotics.
Moving closer to better therapies
The addition of a specialized chemical group that allows CMX410 to permanently attach to its target makes it one of the most selective compounds of its kind. Although more studies are needed before it can be tested in humans, early findings suggest strong potential for future TB treatment.
“These early results are very encouraging,” said Inna Krieger, Ph.D., senior research scientist in Sacchettini’s lab and co-first author of the paper. “Cell wall-targeting antibiotics have long been a cornerstone of tuberculosis treatment. However, after decades of widespread use, their effectiveness is waning due to the rise of drug-resistant strains.
“We are working to discover new drugs that disrupt essential biological processes and identify optimal combinations with existing drugs to enable shorter, safer and more effective treatment regimens. Through these efforts, we hope to help move the world closer to a future free from tuberculosis.”

Adding even a modest number of steps to your daily routine may help delay the advancement of Alzheimer’s disease, especially among those most vulnerable to it, according to new research. In a study published in Nature Medicine, scientists from Mass General Brigham found that greater physical activity was linked to slower cognitive decline in older adults who had higher levels of amyloid-beta, a protein strongly tied to Alzheimer’s.
On average, people who walked between 3,000 and 5,000 steps a day experienced about three years of delay in cognitive decline. Those who walked 5,000 to 7,500 steps per day saw that delay extend to around seven years. In contrast, participants who were largely inactive showed faster accumulation of tau proteins in the brain, which is associated with Alzheimer’s progression, and more rapid declines in thinking skills and daily functioning.
“This sheds light on why some people who appear to be on an Alzheimer’s disease trajectory don’t decline as quickly as others,” said senior author Jasmeer Chhatwal, MD, PhD, of the Mass General Brigham Department of Neurology. “Lifestyle factors appear to impact the earliest stages of Alzheimer’s disease, suggesting that lifestyle changes may slow the emergence of cognitive symptoms if we act early.”
Long-Term Study on Activity and Brain Changes
Researchers examined 296 individuals aged 50 to 90 who showed no cognitive impairment at the start of the Harvard Aging Brain Study. Participants wore waistband pedometers to track physical activity and underwent PET scans to measure amyloid-beta plaques and tau tangles in the brain. They completed yearly cognitive assessments over a period ranging from two to 14 years (average = 9.3 years), and a subset received additional brain scans to monitor changes in tau over time.
The results showed that participants with elevated amyloid-beta who took more daily steps experienced slower cognitive decline and a slower buildup of tau proteins. Statistical modeling indicated that the primary benefit of physical activity came from its association with slower tau accumulation. Among participants with low amyloid-beta levels, there was little evidence of either cognitive decline or tau buildup, and no significant link to activity levels.
Building Cognitive Resilience Through Movement
“We are thrilled that data from the Harvard Aging Brain Study has helped the field better understand the importance of physical activity for maintaining brain health,” said co-author Reisa Sperling, MD, a neurologist at Mass General Brigham and co-principal investigator of the Harvard Aging Brain Study. “These findings show us that it’s possible to build cognitive resilience and resistance to tau pathology in the setting of preclinical Alzheimer’s disease. This is particularly encouraging for our quest to ultimately prevent Alzheimer’s disease dementia, as well as to decrease dementia due to multiple contributing factors.”

The team plans to further explore which types of physical activity are most beneficial, including how intensity and long-term exercise patterns might influence brain health. They also aim to uncover the biological mechanisms that connect physical activity, tau buildup, and cognitive function. The researchers believe these insights could inform future clinical trials that test whether exercise-based interventions can slow cognitive decline in older adults, particularly those at elevated risk for Alzheimer’s.
Empowering People to Take Action
“We want to empower people to protect their brain and cognitive health by keeping physically active,” said first-author Wai-Ying Wendy Yau, MD, a cognitive neurologist at Mass General Brigham. “Every step counts — and even small increases in daily activities can build over time to create sustained changes in habit and health.”
Authorship: In addition to Yau, Chhatwal and Sperling, Mass General Brigham authors include Dylan R. Kirn, Michael J. Properzi, Aaron P. Schultz, Zahra Shirzadi, Kailee Palmgren, Paola Matos, Courtney Maa, Stephanie A. Schultz, Rachel F. Buckley, Dorene M. Rentz, and Keith A. Johnson. Additional authors include Jennifer S. Rabin and Jeremy J. Pruzin.
Disclosures: The authors have no competing interests relevant to the current study. Potential conflicts of interest outside of the submitted work are listed in Nature Medicine.
Funding: This work was supported by the National Institutes of Health (K23 AG084868, K01 AG084816, P01 AG036694, K24 AG035007, R01 AG062667, R01 AG071865, P41EB015896, S10RR021110, S10RR023401, S10RR023043), the Doris Duke Charitable Foundation Clinical Scientist Development Award, and the Massachusetts Life Sciences Center.

Researchers at the Institute of Food Technology (ITAL) and the University of Campinas (UNICAMP) in São Paulo, Brazil, working with colleagues from the Fraunhofer IVV Institute in Germany, have developed a new type of food made from sunflower flour that can serve as a substitute for meat.
The process begins by extracting oil from sunflower seeds. To make the resulting flour safe and digestible for humans, the outer husks and certain phenolic compounds must first be removed. These elements normally give the flour a darker color and make it harder for the body to absorb nutrients effectively.
Creating and Testing the Sunflower-Based Burgers
Researchers prepared two variations of the meat substitute. One was made from flour derived from roasted sunflower grains, while the other used textured sunflower protein. Both formulations were enhanced with tomato powder, spices, and a blend of sunflower, olive, and linseed oils to improve flavor and nutritional value.
The team shaped the mixtures into small burger patties and baked them. They then conducted sensory and physicochemical tests to evaluate the products’ texture, flavor, and composition. Results revealed that the version made from textured sunflower protein had better consistency and higher levels of protein, along with healthy fats such as monounsaturated fatty acids. It also contained impressive mineral levels, providing 49% of the recommended daily intake of iron, 68% of zinc, 95% of magnesium, and 89% of manganese.
Sustainable, Non-GMO Protein Potential
The study, supported by FAPESP, focused on sunflower meal because sunflower oil is already widely used in Europe, and sunflower cultivation is steadily increasing in Brazil. Another advantage is that the plant is not genetically modified, making it an appealing ingredient for consumers seeking non-GMO options.

Sunflower flour also offers a valuable source of plant-based protein, aligning with the growing global demand for sustainable and environmentally friendly food choices.
Mild Flavor and Strong Nutritional Profile
Maria Teresa Bertoldo Pacheco, a researcher at ITAL’s Center for Food Science and Quality and lead author of the paper published in Food Research International, explained that removing the husks and phenolic compounds gives the flour a neutral flavor and aroma. “It should also be noted that, after removing the husks and phenolic compounds, the flour has a very neutral taste and aroma, especially compared to the various vegetable proteins on the market,” she said.
Pacheco also highlighted the favorable balance of essential amino acids in the flour, which adds to its nutritional value. From a technological standpoint, she noted that creating a fibrous structure through processes like extrusion is key to achieving a product with a more authentic, meat-like appearance and texture.
Pacheco emphasized that the research contributes valuable insights for maximizing the use of sunflower cultivars while encouraging appreciation for their nutritional benefits. She also praised the collaboration with German researchers, noting that the partnership fostered technical exchanges, knowledge sharing, and opportunities for students and scientists to work together.

For the first time in Great Britain, there are more over-16s using vapes or e-cigarettes than smoking cigarettes, according to the Office for National Statistics.Some 5.4 million adults use vapes daily or occasionally, compared with 4.9 million using cigarettes, an ONS survey for 2024 suggests.Daily use of vapes is most common among 25-49 year olds, with rising use among women. The popularity of cigarette smoking has been falling for the past decade as the harmful effects of tobacco encouraged many to quit, while less risky vape use has been rising – particularly among younger age groups.Vaping poses a small fraction of the risks of smoking, the NHS says, since cigarettes release thousands of chemicals when they burn, many of which are poisonous and can cause cancer. Switching to vaping reduces those risks.The ONS’s Opinions and Lifestyle Survey suggests that 10% of adults aged 16 and over currently use an e-cigarette every day or occasionally – slightly more than the 9.1% who say they currently smoke.The number saying they’ve given up smoking has risen – 74.2% in 2024, up from 70.3% in 2023.Back in the 1970s, less than 30% had quit the habit. At that time, nearly half of the population were smokers.But much has changed since then. In 2006-2007, a ban on smoking in enclosed public places and workplaces was introduced and in 2015, a ban on smoking in cars with children was brought in.More recently in 2017, plain cigarette packaging was introduced.And government legislation currently progressing through parliament will soon mean anyone born on or after 1 January 2009 will not be legally allowed to buy tobacco in the UK.Rules on how vapes are packaged and displayed in shops are also set to be tightened over concerns that the devices are appealing to children.The ONS survey suggests 6.7% of people aged 16 and over in Great Britain use a vape or e-cigarette every day, up from 5.9% in 2023.Another 3.3% say they use one occasionally.This equates to 5.4 million current vape users, a rise from 5.1 million in 2023.The use of e-cigarettes “daily or occasionally” remained highest among 16 to 24 year olds in Great Britain in 2024 at 13.0%. But this is down from 15.8% in 2023.

A research team at the Institute for Neurosciences (IN), led by Juan Lerma, has uncovered how a distinct group of neurons in the amygdala — a region of the brain involved in processing emotions — contributes to anxiety, depression, and changes in social behavior. The discovery, published in iScience, shows that restoring the balance of neuronal excitability within a precise part of the amygdala can reverse these behavioral changes in mice.
Restoring Brain Balance to Reverse Anxiety
“We already knew the amygdala was involved in anxiety and fear, but now we’ve identified a specific population of neurons whose imbalanced activity alone is sufficient to trigger pathological behaviors,” explains Lerma. His team used a genetically modified mouse model that overexpresses the Grik4 gene, which increases the production of GluK4-type glutamate receptors and heightens neuronal excitability. These mice, developed by the same laboratory in 2015, displayed anxiety and social withdrawal similar to symptoms seen in people with conditions such as autism or schizophrenia.
The researchers were able to normalize Grik4 expression specifically in neurons located in the basolateral amygdala. This adjustment reestablished normal communication with a group of inhibitory neurons in the centrolateral amygdala known as “regular firing neurons.” “That simple adjustment was enough to reverse anxiety-related and social deficit behaviors, which is remarkable,” says Álvaro García, the study’s first author.
The team assessed the animals using electrophysiological recordings and behavioral tests designed to measure anxiety, depression, and social interaction. These tests evaluate traits such as the preference for open or enclosed spaces and interest in unfamiliar mice. Using genetic engineering tools and modified viruses, the scientists precisely corrected the dysfunction in the basolateral amygdala and tracked changes in both neuronal activity and overall behavior.
Widespread Effects Beyond Genetic Models
The researchers then applied the same approach to normal (wild-type) mice that naturally showed higher anxiety levels. The treatment also reduced their anxiety. “This validates our findings and gives us confidence that the mechanism we identified is not exclusive to a specific genetic model, but may represent a general principle for how these emotions are regulated in the brain,” Lerma notes.
Some cognitive deficits, such as problems with object recognition memory, were not corrected, suggesting that other regions like the hippocampus may also play a role in these disorders. Even so, the results open promising new avenues for therapy. “Targeting these specific neural circuits could become an effective and more localized strategy to treat affective disorders,” Lerma concludes.
This research was supported by the Spanish State Research Agency (AEI) — Spanish Ministry of Science, Innovation and Universities, the Severo Ochoa Excellence Program for Research Centers at the Institute for Neurosciences CSIC-UMH, the European Regional Development Fund (ERDF), and the Generalitat Valenciana through the PROMETEO and CIPROM programs.

Scientists have discovered that the human brain has its own built-in pain map, activating different regions when easing pain in the face, arms, or legs. Placebo pain relief only works in the exact area where the brain expects it to happen. Understanding this system could lead to safer, more precise treatments that target pain exactly where it occurs.Mapping the Brain’s Hidden System for PainResearchers at the University of Sydney have revealed a brainstem network that manages pain differently depending on where it occurs in the body. Using placebo pain relief, they discovered a map-like system that fine-tunes pain control for specific regions, such as the face, arms, or legs. The findings could lead to safer and more precise pain therapies that avoid the risks of opioid-based treatments.
The brainstem functions as the main communication pathway between the brain and spinal cord, directing signals that control thought, sensation, and survival responses. It also produces most of the brain’s vital neurochemicals, making it a central hub for regulating both physical and emotional states.
Published in Science, the study used 7-Tesla functional magnetic resonance imaging (fMRI) (one of the most advanced brain scanners available, with only two in Australia) to identify how two major regions of the brainstem coordinate pain relief through placebo responses.
Dr. Lewis Crawford, lead author and research fellow at the School of Medical Sciences and the Brain and Mind Centre, explained, “This is the first time we’ve seen such a precise and detailed pain map in the human brainstem, showing us that it tailors pain relief to the specific part of the body that’s experiencing it.”
This breakthrough builds on decades of research led by co-author Professor Kevin Keay, Deputy Head of the School of Medical Sciences, who has long studied the brain’s role in pain regulation.

How the Placebo Effect Reveals the Brain’s Pain Control
To explore how the brain organizes pain relief, researchers tested 93 healthy volunteers by applying heat to different parts of their bodies. A placebo cream was used on some areas, but scientists secretly lowered the temperature to convince participants that the cream was reducing pain.
Each participant’s heat level was personalized to reach a moderate level of discomfort, based on a scale from 0 (no pain) to 100 (worst pain imaginable), typically between 40 and 50 degrees Celsius.
When the same heat stimulus was later reapplied, participants continued to feel less pain in the areas where the placebo cream had been used, even though the temperature was no longer reduced. About 61 percent reported this effect, a strong indication of genuine placebo-driven pain relief.
Dr. Crawford noted, “We found that upper parts of the brainstem were more active when relieving facial pain, while lower regions were engaged for arm or leg pain.”
Pinpointing the Brain’s Pain-Relief Centers
Two major brainstem regions, the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM), were identified as central to this system. Each showed distinct patterns of activity depending on where the pain occurred. Upper sections of the PAG and RVM responded to facial pain, while lower sections activated for pain in the limbs.

According to Dr. Crawford, “The brain’s natural pain relief system is more nuanced than we thought. Essentially, it has a built-in system to control pain in specific areas. It’s not just turning pain off everywhere; but working in a highly coordinated, anatomically precise system.”
A Blueprint for Targeted Pain Therapies
Understanding which brainstem areas are linked to different parts of the body may open new avenues for developing non-invasive therapies that reduce pain without widespread side effects.
“We now have a blueprint for how the brain controls pain in a spatially organized way,” said Professor Luke Henderson, senior author and Professor in the School of Medical Sciences and the Brain and Mind Centre. “This could help us design more effective and personalized treatments, especially for people with chronic pain in a specific area of their body.”
The study also challenges long-held assumptions about how placebo pain relief works. Instead of relying on the brain’s opioid system, experts say a different part of the brainstem — the lateral PAG — is not only responsible but works without using opioids and could instead be linked to cannabinoid activity.
“Opioid-based pain relief typically activates central areas of the brain and can affect the whole body, whereas the cannabinoid circuit that we identified appears to operate in more targeted regions of the brainstem,” said Dr. Crawford. “This supports the idea that cannabinoids may play a role in localized, non-opioid pain control.”
“Knowing exactly where pain relief is happening in the brain means we can target that area or assess whether a drug is working in the right place,” said Dr. Crawford. “This could lead to more precise treatments for chronic pain that don’t rely on opioids and work exactly where the brain expects pain relief to occur — a huge step forward for pain management.”

A large review of health data from more than 130,000 adults with insomnia found that people who took melatonin for a year or longer were more likely to develop heart failure, be hospitalized for the condition, or die from any cause compared to those who didn’t take the supplement. While the study cannot prove that melatonin directly causes these outcomes, the strong association raises important safety questions about long-term use of this popular sleep aid. Researchers emphasize that more studies are needed to fully understand melatonin’s impact on heart health and ensure it can be used safely.Long-Term Melatonin Use Linked to Higher Heart Failure RiskPeople who regularly take melatonin to improve sleep may face serious health risks. A preliminary study presented at the American Heart Association’s Scientific Sessions 2025 found that adults with chronic insomnia who used melatonin for a year or longer were more likely to develop heart failure, be hospitalized for heart failure, and die from any cause than those who did not take the supplement. The findings will be discussed at the AHA’s annual meeting, taking place Nov. 7-10 in New Orleans, a leading international event for cardiovascular science and clinical research updates.
Melatonin is a hormone produced by the pineal gland that regulates the body’s sleep-wake cycle. Its levels naturally rise in the dark and drop during daylight hours. Synthetic melatonin, which is chemically identical to the natural hormone, is widely used to treat insomnia (difficulty falling and/or staying asleep) and jet lag. In many countries, including the U.S., melatonin supplements can be purchased over the counter. However, because they are not regulated in the U.S., products can differ widely in purity and dosage.
How the Study Was Conducted
Researchers divided participants into two groups based on their medical records. Those who had taken melatonin for at least one year were classified in the “melatonin group,” while individuals with no record of melatonin use were placed in the “non-melatonin group.”
“Melatonin supplements may not be as harmless as commonly assumed. If our study is confirmed, this could affect how doctors counsel patients about sleep aids,” said Ekenedilichukwu Nnadi, M.D., lead author of the study and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York.

Investigating Heart Failure and Sleep Aid Safety
Although melatonin is marketed as a safe and natural sleep remedy, little evidence exists on its long-term cardiovascular effects. The research team wanted to know whether long-term use could influence heart failure risk in people with chronic insomnia. According to the American Heart Association’s 2025 Heart Disease and Stroke Statistics, heart failure occurs when the heart cannot pump enough oxygen-rich blood to sustain the body’s organs. The condition affects about 6.7 million U.S. adults.
To explore this question, scientists used data from the TriNetX Global Research Network, an international database of de-identified medical records. They reviewed five years of data on adults diagnosed with chronic insomnia who had documented melatonin use for more than a year. Each was matched with another person who also had insomnia but had never used melatonin. Individuals with a previous diagnosis of heart failure or who had been prescribed other sleep medications were excluded.
The main analysis found: Among adults with insomnia, those whose electronic health records indicated long-term melatonin use (12 months or more) had about a 90% higher chance of incident heart failure over 5 years compared with matched non-users (4.6% vs. 2.7%, respectively). There was a similar result (82% higher) when researchers analyzed people who had at least 2 melatonin prescriptions filled at least 90 days apart. (Melatonin is only available by prescription in the United Kingdom.)A secondary analysis found: Participants taking melatonin were nearly 3.5 times as likely to be hospitalized for heart failure when compared to those not taking melatonin (19.0% vs. 6.6%, respectively). Participants in the melatonin group were nearly twice as likely to die from any cause than those in the non-melatonin group (7.8% vs. 4.3%, respectively) over the 5-year period.”Melatonin supplements are widely thought of as a safe and ‘natural’ option to support better sleep, so it was striking to see such consistent and significant increases in serious health outcomes, even after balancing for many other risk factors,” Nnadi said.

Expert Reactions and Caution From Sleep Researchers
“I’m surprised that physicians would prescribe melatonin for insomnia and have patients use it for more than 365 days, since melatonin, at least in the U.S., is not indicated for the treatment of insomnia. In the U.S., melatonin can be taken as an over-the-counter supplement and people should be aware that it should not be taken chronically without a proper indication,” said Marie-Pierre St-Onge, Ph.D., C.C.S.H., FAHA, chair of the writing group for the American Heart Association’s 2025 scientific statement, Multidimensional Sleep Health: Definitions and Implications for Cardiometabolic Health. St-Onge, who was not involved in this study, is a professor of nutritional medicine in the division of general medicine and director of the Center of Excellence for Sleep & Circadian Research in the department of medicine at Columbia University Irving Medical Center in New York City.
The study has several limitations. First, the database includes countries that require a prescription for melatonin (such as the United Kingdom) and countries that don’t (such as the United States), and patient locations were not part of the de-identified data available to the researchers. Since melatonin use in the study was based only on those identified from medication entries in the electronic health record, everyone taking it as an over-the-counter supplement in the U.S. or other countries that don’t require a prescription would have been in the non-melatonin group; therefore, the analyses may not accurately reflect this. Hospitalization figures were also higher than those for initial diagnosis of heart failure because a range of related diagnostic codes may be entered for the hospitalization, and they may not always include the code for a new diagnosis of heart failure. The researchers also lacked information on the severity of insomnia and the presence of other psychiatric disorders.
“Worse insomnia, depression/anxiety or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk,” Nnadi said. “Also, while the association we found raises safety concerns about the widely used supplement, our study cannot prove a direct cause-and-effect relationship. This means more research is needed to test melatonin’s safety for the heart.”
Study details, background and design: The study included 130,828 adults (average age of 55.7 years; 61.4% women) diagnosed with insomnia. The study data was from TriNetX, established in 2013, a growing global network of real-world, de-identified patient data available for research. 65,414 participants had been prescribed melatonin at least once and reported taking it for at least a year. A second group of people were examined for comparison (control group) — those who had never been prescribed melatonin and were matched to the group taking melatonin on 40 factors including demographic information, health conditions and medications. Participants were excluded if they had already been diagnosed with heart failure or had been prescribed other types of sleeping pills such as benzodiazepines. The melatonin and control groups were matched for age, sex, race/ethnicity, heart and nervous system diseases, medications for heart and nervous system diseases, blood pressure and body mass index. Researchers looked at electronic medical records from the five years after the matching date. For the main findings, records were searched for codes related to an initial diagnosis of heart failure. Secondary findings included codes for hospitalization related to heart failure or death. Following the initial analyses, researchers validated the credibility of their findings by conducting a sensitivity analysis. This involved slightly changing the criteria: they required participants in the melatonin group to have filled at least two melatonin prescriptions that were at least 90 days apart. This adjustment aimed to determine whether the extended duration of confirmed melatonin prescriptions influenced the outcomes.Note: The study featured in this article is a research abstract. Abstracts presented at American Heart Association’s scientific meetings are not peer-reviewed, and the findings are considered preliminary until published as full manuscripts in a peer-reviewed scientific journal.

The network of tiny blood vessels within the eyes may offer powerful clues about a person’s risk of heart disease and how quickly their body is aging, according to new research from McMaster University and the Population Health Research Institute (PHRI), a joint institute of Hamilton Health Sciences and McMaster.
Published in Science Advances on October 24, 2025, the study suggests that simple retinal scans could eventually serve as a non-invasive tool to evaluate both cardiovascular health and biological aging. Such scans may one day help doctors detect problems early and guide preventive care before symptoms appear.
Linking the Eyes, Genes, and Blood
“By connecting retinal scans, genetics, and blood biomarkers, we have uncovered molecular pathways that help explain how aging affects the vascular system,” says Marie Pigeyre, senior author of the study and an associate professor in McMaster’s Department of Medicine.
According to Pigeyre, the eye provides an accessible and unique view into the body’s circulatory system. “Changes in the retinal blood vessels often mirror changes occurring throughout the body’s small vessels,” she explains.
To explore these relationships, the researchers analyzed retinal images, genetic profiles, and blood samples from more than 74,000 participants drawn from four large-scale studies: the Canadian Longitudinal Study on Aging (CLSA), the Genetics of Diabetes Audit and Research Tayside Study (GoDARTS), the UK Biobank (UKBB), and the PHRI Prospective Urban Rural Epidemiological (PURE) study.
Their analysis revealed that individuals with simpler and less branched retinal vessels tended to have a higher likelihood of cardiovascular disease. These same individuals also showed biological signs of accelerated aging, including increased inflammation and a reduced lifespan.

Today, evaluating conditions related to aging such as heart disease, stroke, and dementia usually requires multiple, complex tests. Researchers hope that retinal imaging could one day simplify this process, providing a fast and accessible measure of both aging and cardiovascular risk. However, they note that for now, such scans are just one part of a broader clinical picture that still requires comprehensive testing.
Discovering Molecular Clues Behind Aging
A deeper look at blood biomarkers and genetic data revealed more than simple associations — it pointed to biological mechanisms that may drive these changes. Researchers identified several key proteins linked to inflammation and vascular aging, suggesting new avenues for drug development.
Among the most notable proteins were MMP12 and IgG-Fc receptor IIb, both associated with age-related damage in blood vessels. According to Pigeyre, these molecules could represent promising therapeutic targets.
“Our findings point to potential drug targets for slowing vascular aging, reducing the burden of cardiovascular diseases, and ultimately improving lifespan,” Pigeyre says.
The study drew on blood protein biomarker data from the PHRI-led Prospective Urban and Rural Epidemiological study, an international research initiative.
Funding for the project came from the Canadian Institutes of Health Research, the E.J. Moran Campbell Internal Career Research Award from McMaster University, and the Early Career Research Award from Hamilton Health Sciences (HHS). Retinal image analyses conducted through the CLSA were additionally supported by an HHS New Investigator Fund.

The human digestive system relies on two main kinds of macrophages, a type of specialized white blood cell, to maintain intestinal health. One group, the inflammatory macrophages, attacks harmful microbes, while the other, the non-inflammatory macrophages, repairs tissue and promotes healing. In Crohn’s disease (a chronic form of inflammatory bowel disease, or IBD), this balance breaks down. When the inflammatory type dominates, the result is persistent inflammation that damages the intestinal wall and causes pain and other symptoms.
Scientists at the University of California San Diego School of Medicine have created a new method that combines artificial intelligence (AI) with cutting-edge molecular biology tools to uncover what determines whether a macrophage becomes inflammatory or restorative.
Their research also sheds light on a mystery that has puzzled scientists for decades: how a gene known as NOD2 influences this process. Discovered in 2001, NOD2 was the first gene linked to an increased risk of Crohn’s disease.
Mapping the Gut’s Genetic Blueprint
Using advanced machine learning, the team examined thousands of macrophage gene expression profiles taken from both healthy colon tissue and tissue affected by IBD. This analysis revealed a genetic signature made up of 53 genes that consistently distinguished between aggressive, inflammatory macrophages and those responsible for repairing tissue.
Among these 53 genes, one encodes a protein called girdin. The researchers discovered that in non-inflammatory macrophages, a particular part of the NOD2 protein attaches to girdin. This interaction helps keep inflammation under control, removes harmful bacteria, and allows tissue to heal. However, the most common Crohn’s disease mutation in the NOD2 gene deletes the section where girdin normally binds. Without that connection, the system becomes unbalanced, tipping toward chronic inflammation.
“NOD2 functions as the body’s infection surveillance system,” said senior author Pradipta Ghosh, M.D., professor of cellular and molecular medicine at UC San Diego School of Medicine. “When bound to girdin, it detects invading pathogens and maintains gut immune balance by swiftly neutralizing them. Without this partnership, the NOD2 surveillance system collapses.”
Testing the Discovery in Animal Models

To confirm their findings, the scientists compared mouse models of Crohn’s disease that lacked the girdin protein with those that still had it. The mice missing girdin developed severe gut inflammation and an altered microbiome, and many died from sepsis, a dangerous condition caused by an uncontrolled immune response that inflames the entire body and harms vital organs.
“The gut is a battlefield, and macrophages are the peacekeepers,” said co-first author Gajanan D. Katkar, Ph.D., assistant project scientist at UC San Diego School of Medicine. “For the first time, AI has allowed us to clearly define and track the players on two opposing teams.”
Toward New Treatments for Crohn’s Disease
By merging AI-based analysis, biochemical research, and animal experiments, the study resolves one of the longest-standing questions in Crohn’s disease research. The findings explain how a crucial genetic mutation drives inflammation and could guide the development of new therapies aimed at restoring the lost partnership between girdin and NOD2.
The study was published on October 2 in the Journal of Clinical Investigation.

8 hours agoShareSaveGeorgia RobertsPolitical Correspondent ShareSaveSUPPLIEDNatalie Rowntree from North Yorkshire has recently started her IVF journey, and describes the process as “intense”.The 38-year-old has had seven IVF-related appointments in the space of eight weeks, including multiple blood tests, scans and X-rays, one of which left her in physical discomfort for “a good few days”.As is the nature of fertility treatment, all of these appointments have to be done at very specific times of the month – and fitting this around her job at a private opticians has proven difficult.”I’ve just been using sick days and holidays to go through these appointments,” she says.Added to this is the emotional toll of having to manage the process, with no entitlement to time off.Two years ago, Natalie had two miscarriages over a six month period and since then has not been able to conceive with her partner.”The emotion side is quite difficult, and then trying to manage that around work…do I bite the bullet and explain what’s happening? Or keep having sick days and holidays?” she says.According to research from the social enterprise Fertility Matters at Work, Natalie is one of the around 63% of employees undergoing IVF who are taking sick leave to undergo treatment – with most citing they were doing so to hide their treatment from their employer.Now there are calls for women undergoing fertility treatments to have the legal right to paid time off to attend their appointments.Campaigners claim that while some employers offer fertility support, it is unequal and not guaranteed, and should be classed as a medical procedure.Becoming pregnant through IVF enables the same maternity rights as non-IVF pregnancies, but currently in employment law there are no legal rights when it comes to fertility treatment.According to new research by Fertility Matters at Work, that comes at a potential cost of millions to the economy and businesses in lost productivity.Natalie says she has avoided bringing her treatment up with her managers because she is nervous about the reception she might get for taking time off work to go through the process.”If I was to go to my managers and say I was pregnant, I wouldn’t feel nervous at all about that…but with this, because you don’t know how long it’s going to go on for, you can’t give work a timescale.”Employment guidance from the Equality and Human Rights Commission advises “good practice” to employers with workers seeking leave for IVF treatment, but it acknowledges that such requests are not covered by the protected characteristic of pregnancy and maternity in law.However, refusing to grant someone leave for fertility treatment could count as sex discrimination in certain situations – but campaigners say this is hard to prove.’Employers could benefit too’Becky Kearns, from Fertility Matters at Work, co-founded the group with two other women after they all experienced their own difficulties undergoing IVF whilst trying to keep afloat in the workplace.The 39-year-old says providing time off would be a potential benefit of employers, who could save the economy millions in lost productivity.”What we’re finding is, because there’s 63% taking sick leave, that is having an impact on businesses, there’s a cost for the disruption of this absence.”She also thinks employers need to be more aware of the toll IVF – which she considers a “significant life event” – can take on their employees.”You often have a number of very short notice appointments you have to attend, it’s very dependent on how your body is responding to medication.”But we also know there’s still a huge amount of stigma that surrounds IVF and infertility.”We receive messages almost daily from people who are struggling with this experience…people taking sick leave to hide treatment, the fact that they’re then triggered on absence procedures and potentially having their performance monitored.”And it was all because they were going through fertility treatment and just felt unable to say that was what they were going through.”She says women have also told them they have left jobs and signed non-disclosure agreements as a result of going through IVF. EMOTIVE EYEThe government says that while no specific legal right to time off for IVF treatment exists, it expects employers to treat staff fairly and accommodate reasonable requests.The government also says it is strengthening flexible working rules which will make it easier for employees to agree arrangements with their workplace for support.But that isn’t enough reassurance for the Labour MP Alice MacDonald, who will be introducing the issue in Parliament via a ten minute rule bill, which proposes to put into law the legal right to time off for fertility appointments.Whilst it is unlikely the issue becomes law without official government backing, she is seeking to get it “firmly on the government’s radar”.”Many people, especially women, are impacted by this when you’re trying to have a baby and through no fault of your own, you need that extra medical support, you don’t have a right to time off to go to those appointments,” she says.”At a time when you are hoping that it’s going to work, hoping it’s going to be successful, finally be pregnant and have the baby you’ve wanted you’ve got another additional barrier which is with your employer.”There are many employers who are supportive but you have to hope you’ve got one that understands and who will give you the time off.”If it was clearly in law what your rights are we think it opens up that conversation and employers would have to have a policy.”‘Striking a balance’Patrick Milnes from the British Chambers of Commerce says there is a concern amongst businesses about the potential for “over legislation” in anticipation of the Employment Rights Bill in particular, which will seek to ease rules on flexible working.”Small and medium businesses in particular have been talking to us about how concerned they are about navigating different types of legislative leave,” he says.”Most employers that we speak to are doing this kind of thing anyway as a matter of good practice.”If you legislate, those processes can become more complicated it can become more burdensome, and actually in many instances it’s easier to do these things on a case by case, ad hoc basis.”There’s a middle ground between having nothing at all and having a full legislated process that might be overwhelming in some instances.”But Natalie says legal rights to time off would make a “huge” difference to her.”If you didn’t have to think about, ‘what are work going to think about me being off again?’ it would take a lot of the stress away.”I’m at the beginning stages [of IVF] and I’m thinking about what it’s going to look like work-wise going forward. “I don’t want this to be a thing forever, for other women that are also going to go through it. I think it’s an important thing that needs to be fixed.”