Traumatic brain injury in Pakistan linked to poor long-term survival

Weill Cornell Medicine

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Dr. Junaid Razzak

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Credit: Weill Cornell Medicine

Traumatic brain injury (TBI) in Pakistan is associated with a high risk of death and disability long after the initial injury, even in mild to moderate cases, according to two new studies in JAMA Network Open led by Weill Cornell Medicine researchers. While most TBIs occur in low- and middle-income countries due to road traffic accidents, long-term patient outcomes remain poorly understood.

To shed light on this critical issue, the researchers analyzed data from a trauma registry of all injured patients from two care centers in Karachi, Pakistan, from December 2021 to May 2024. The studies followed patients for a year after injury, providing one of the most detailed pictures to date of what happens after TBI in a resource-limited setting.

The first study, published Aug. 11, focused on patients with severe to moderate TBI. A second paper, published Aug. 13, looked at outcomes of mild traumatic brain injuries. Together, the studies found that the consequences of brain injury depend on more than severity at admission and many patients remain vulnerable after leaving the hospital.

“We found that TBIs are responsible for a high number of trauma-related deaths in Pakistan, even with more mild to moderate injuries, which we were not expecting,” said senior author Dr. Junaid Razzak, professor of emergency medicine at Weill Cornell and an emergency medicine physician at NewYork-Presbyterian/Weill Cornell Medical Center. “Patients are falling through gaps in the trauma care system before, during and especially after hospitalization.”

The study suggests that many deaths and disabilities could potentially be prevented in Pakistan and similar low- and middle-income countries with stronger trauma systems, including faster access to appropriate care, structured post-discharge monitoring and expanded rehabilitation services.

Focusing on the First Month After Discharge

Clinicians use the Glasgow Coma Scale (GCS), a 15-point measure of eye, verbal and motor responses to gauge how alert patients are after a head injury. Severe TBI, a score of 3 to 8, means people cannot follow commands or respond to pain and may have trouble with their airway. Moderate TBI, a score of 9 to 12, means patients may be confused but can still respond to simple commands.

The first study focused on 819 registry patients diagnosed with moderate (45%) to severe (55%) TBI based on the GCS. As expected, patients with severe injuries faced the greatest risk of death and disability. However, researchers were surprised by the poor outcomes among patients with moderate injuries, who would typically be expected to have a better chance of recovery.

Many deaths occurred during the first month after discharge, suggesting that patients remain vulnerable during the transition from hospital care to life at home. At 12 months, mortality reached nearly 60% in patients with moderate TBI and almost 88% among those with severe injury. In comparison, a previous study in high-income countries found respective mortality rates of 9% and 30%.

For both studies, the researchers found that older age, no surgical intervention and greater injury severity were associated with a higher risk of death.

Telehealth and regular remote follow-up may be a practical way to monitor recovery and identify complications early, proposed the authors.

Reconsidering How "Mild" TBI Is Defined

The second study assessed 602 registry patients with mild TBI, defined as a GCS of 13 to 15. These patients tend to be awake and can follow commands but may experience brief confusion or memory loss.

The researchers found that not all mild TBIs had the same prognosis. Some patients at the lower end of the GCS mild range experienced substantially worse outcomes, including higher mortality and poorer quality of life during recovery, than those who scored 15. Potentially, some injuries classified and treated as mild may have actually been more serious, said the authors. In addition, premature hospital discharge may have contributed to this finding, as patients stayed approximately two days.

Overall, the 12-month mortality rate was 14% for all groups in the second study, which is relatively high, compared to higher-income countries in the published literature.

“My hunch is that even people with mild disabilities, who are already living at the edge of poverty, fall below the poverty line when they can't work or perform basic tasks,” Dr. Razzak said. “Then their access to basic healthcare and ability to take care of themselves drops significantly.”

Future Research

“A broken 'chain of survival’ exists, in which bystanders don't know how to respond to an accident, ambulance drivers don't know which hospitals have open beds and emergency room healthcare providers race against the clock,” Dr. Razzak said. “Treatment in the first 48 hours is critical for better outcomes.”

Dr. Razzak plans to research how trauma care systems can be designed and better equipped to get patients to the right facilities. “By making this issue more visible to the government, we hope these gaps can be fixed, saving a significant number of lives," he said.

 

This research was funded by the Fogarty International Centre of the National 3 Institutes of Health under award No. D43TW007292—The Aga Khan University Trauma and 4 Injury Research Training Program; this funding solely supported data collection.

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Journal

JAMA Network Open

Study overturns 100-year-old assumption about common bacteria in the lungs

New findings raise questions about function of lung microbiome residents

Michigan Medicine - University of Michigan

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Our bodies are teeming with more than 35 trillion bacteria, coexisting in microbiomes inside our guts, mouths, lungs, skin and urogenital tract.

While it’s now clear these microbes are associated with health and disease, scientists have only begun to uncover the full scale of their biology and functions.

In a striking example of just how much is still unknown, a new University of Michigan study overturns a 100-year-old assumption about one common bacterial resident of the lungs, Prevotella melaninogenica.

The lab led by Ariangela Kozik, Ph.D., Assistant Professor of Internal Medicine at U-M Medical School and Assistant Professor of Molecular, Cellular and Developmental Biology at U-M, is interested in Prevotella because the bacteria are commonly found in the respiratory tract and reportedly associated with all manner of chronic conditions, yet also found in healthy people. It's also widely thought to be an obligate anaerobe, incapable of surviving in the presence of oxygen.

What, they wondered, is it doing in the lungs?

Kozik, an asthma researcher, notes that Prevotella are found differing amounts inside the respiratory tract in both healthy people and in people with asthma and COPD, accounting for roughly 10% of microbial populations in healthy lungs and up to 13% on average, in individuals with respiratory disease.

To unravel this paradox, Kozik’s team subjected cultures of P. melaninogenica to increasing percentages of oxygen, comparing the rates of growth and survival.

They found that the upper threshold for growth was between 5-8% oxygen, and the bacteria could briefly survive oxygen levels as high as 21%.

Furthermore, the study found, using a new real-time sensor platform and RNA sequencing, that Prevotella appear to be consuming oxygen and dealing with oxidative stress and DNA damage differently than other aerobic bacteria.

“Prevotella has all of these mechanisms to allow it to survive in oxygenated environments that previously were not appreciated for this organism at all, changing what we thought we knew,” said Kozik.

The ability to exist in the presence of oxygen may lie along a spectrum and not be as clear cut as scientists have traditionally defined, she notes.

Kozik and her lab hope to next interrogate how the immune system responds to Prevotella and dive deeper into lung bacteriology to understand specifically how these microbes affect the body.

“We need to work to look at the bacterial community and ask, how does this community function currently? What metabolites are they making, what signals are they sending to the immune system? How's the immune system responding to it? How does this activity differ in health versus in the context of chronic lung diseases?” said Kozik.

This deeper understanding of the body’s various microbiomes could help drive more targeted therapies, she adds.

“Those kinds of questions about the relationships between bacteria and the body are what is a big black box right now.”

Additional authors: Claire Albright, Gouri Anil, Jacob Evans and Souzane Ntamubano

Michigan Research Core(s): MCDB Imaging Core, MCDB Biomolecular Science Facility, Advanced Genomics Core

Paper cited: “Aerotolerant capacity of the lung symbiont Prevotella melaninogenica,” The Journal of Bacteriology. DOI: 10.1128/jb.00142-26

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Journal

Journal of Bacteriology

DOI

10.1128/jb.00142-26 

 

A new Bournemouth University study reveals how ‘pioneering pairs’ of ospreys drive population recovery

Bournemouth University

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Dorset Osprey

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Credit: Birds of Poole Harbour

A new study by Bournemouth University (BU) has discovered that faster recovery of osprey populations relies on a small number of ospreys who, unlike most, prefer to nest away from others of the same species. These birds have been referred to as ‘pioneering pairs’ and could be the secret to helping conservationists increase their population spread. 

The study looked at a rare long-term dataset covering 54 years of recolonisation of ospreys in Northern Scotland. It investigated the distribution and density of nests and the resulting patterns of settlement to understand how populations spread and what drives spatial recovery. 

The study was led by PhD Researcher at BU, Brittany Maxted, in collaboration with Dorset charity, Birds of Poole Harbour and The Roy Dennis Wildlife Foundation who monitor ospreys in parts of Northern Scotland. Brittany said: “Ospreys usually like to nest in areas where there are already other ospreys, which we refer to as conspecific attraction. Most males also exhibit natal philopatry, which means they tend to breed close to their own birthplace. Together, these factors lead to very slow population spread for such a large bird. However, in Scotland we noticed that a small number of pairs were choosing to settle more than 20 km away from all the others, in areas with no competition. We call these ‘pioneering pairs’ as they recolonise new areas, and in doing so create separate subpopulations and increase the speed of recovery for the species.” 

Restoring lost species is a key goal for conservationists, but very little is known about the process of recolonisation. This study found that the patterns seen in ospreys are very similar to other types of population expansion which have been much better studied, like invasive species. The tools that scientists use to investigate these species could therefore also be used to better understand and help recovering species. 

The paper’s findings also point to other potential solutions to speed up the recovery of osprey populations. Dr Tim Mackrill, Lead Ornithologist at the Roy Dennis Wildlife Foundation and co-author on the paper said: “This study highlights how much the spatial expansion of ospreys relies on the long-distance dispersal of these rare pioneering individuals. It suggests that the best way to accelerate natural recovery rates is for conservationists to encourage or even replicate these pioneering movements. We can do this by building artificial nests to help entice ospreys into new areas or by physically moving individuals via translocation.” 

Ospreys once bred across much of Britain, but by 1916 they had disappeared due to hunting and egg collecting. However, after a pair naturally returned to a nest site at Loch Garten in Scotland in 1954, a conservation movement began to protect nesting pairs and help the species recover. Dr Roy Dennis OBE, founder of the Roy Dennis Wildlife Foundation has been monitoring and conserving the Scottish population since the 1960s, leading to the dataset behind this study. Roy said: “It’s fantastic that this dataset, which we’ve collected over many decades, continues to teach us more about these remarkable birds. Our findings reinforce that we’re taking the right approach to restore ospreys across the UK and beyond, and suggest that we should be using these measures even more widely to see faster recovery of the species across Europe.” 

One example of where these techniques have already helped ospreys recover is in Poole Harbour in Dorset. Starting in 2017, the Roy Dennis Wildlife Foundation and Birds of Poole Harbour ran a five-year translocation project in collaboration, moving young ospreys from Northern Scotland to Poole Harbour. Healthy chicks were taken from longstanding nests at seven weeks old and moved temporarily to hacking cages in Dorset to finish developing before being released into the surrounding landscape, which they quickly came to recognise as home. Brittany said: “Through translocation we can essentially create our own pioneering birds to kickstart a new population. The first breeding pair in Poole Harbour was a male named 022 who we had translocated from Scotland, and a female named CJ7 who had visited from a population 200 km away and was attracted to stay by the presence of translocated chicks. In 2022 they hatched two chicks of their own, becoming the first breeding ospreys in Southern England since 1847. If it wasn’t for the translocation project, we may have had to wait another 60 years for breeding ospreys to reach Dorset naturally.” 

The team and volunteers have described it as a “huge success story” with the original Poole Harbour pair returning to breed and producing chicks at the same nest each year since. This summer they have hatched four chicks for the third year in a row, all of which will remain in the area and reliant on their parents for food until they leave on migration around early September. And several pioneering movements have also been recorded, with a second pair breeding away from the harbour and the first wild born Poole Harbour chick now breeding in the East Midlands. Both pairs are forming new subpopulations and starting to close the gap between Poole Harbour and the nearest osprey population in Rutland Water. 

Brittany, who is currently leading a team of Birds of Poole Harbour staff and volunteers who monitor the growing population said: “Translocation is an incredible tool, but it can take many years to see the results. We’re still in the early stages in Dorset, but are already seeing some of the first wild born chicks returning, with four eligible young males currently exploring suitable nest sites and looking for mates. We hope that in the coming years some of them will become pioneers themselves, helping the population spread along the south coast of England. Artificial nests have already been built for them in neighbouring counties like Devon and Hampshire, and based on the results of our study we’ll be aiming to provide lots more.” 

Brittany and her co-authors hope that their research will help motivate more conservation action for ospreys across Europe, where they are still missing from much of their historical range. They also have many more questions about what determines where ospreys choose to nest and what makes pioneering pairs different, which they plan to investigate in the future. 

The full study has been published in the Journal of Animal Ecology. To find out more about the conservation of ospreys and where to see them in Dorset visit the Roy Dennis Wildlife Foundation and Birds of Poole Harbour website.  

For further information about courses in Ecology & Wildlife Conservation please visit the BU website. 

 

Dorset Osprey

Credit

Mark Wright

 

Webcam picture taking in 2024 showing female osprey, far right (CJ7) and male osprey, second right (022), with four chicks.

Credit

Birds of Poole Harbour

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Journal

Journal of Animal Ecology

DOI

10.1111/1365-2656.70322 

Method of Research

Observational study

Subject of Research

Animals

Article Title

A new Bournemouth University study reveals how ‘pioneering pairs’ of ospreys drive population recovery

Article Publication Date

13-Aug-2026

 

Mutation hotspots help 'friendly' viruses outmaneuver the bacteria in your gut

Could we harness their chameleon-like nature to treat infections when antibiotics don’t work?

Michigan State University

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Certain bacteriophages found in the human gut have mutation hotspots scattered throughout their genomes that help them modify key defense genes, researchers report.

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Credit: Sundharraman Subramanian and Alaina Pabbathi, Cryo-EM Core Facility, Michigan State University

Every 15 minutes, someone in the U.S. dies of a drug-resistant superbug. A few decades from now, antibiotic-resistant bacterial infections threaten to become the leading cause of death worldwide, outpacing cancer.

In the race for a solution to the antibiotic resistance crisis, a century-old practice is attracting renewed interest. The treatment, called phage therapy, involves co-opting friendly viruses that kill bacteria but ignore human cells.

Bacteria can — and do — develop resistance to phages, just as they do with antibiotics. But unlike antibiotics, phages can evolve counter defenses of their own.

Now, researchers at Michigan State University have identified a counter defense used by a group of phages common in the human gut, called Enterobacteria phage T2, that helps them stay one step ahead of their bacterial hosts.

These phages have mutation hotspots scattered throughout their genomes that help them modify key defense genes, the researchers report.

In a study published Aug. 13 in the journal Nature Microbiology, they show that these mutation hotspots help diversify their progeny to employ different survival strategies, ensuring that at least some continue to infect and kill no matter what countermeasures their bacterial hosts throw at them.

“They’re essentially hedging their bets,” said co-author Chris Waters, a core faculty member in MSU’s Ecology, Evolution, and Behavior program.

“If we can harness these kinds of evolutionary tricks, we might be able to make more effective phage therapies in response to the antibiotic resistance crisis,” Waters added.

The idea of using phages in medicine isn’t new. Cocktails of phages have been used since the 1920s to treat dysentery, sepsis, pneumonia and other ailments, particularly in France, Poland and parts of the former Soviet Union.

Interest in phage therapy waned in the West after the discovery of penicillin and other chemical antibiotics in the 1940s. But now, with deadly microbes from MRSA to tuberculosis becoming resistant to more and more of these drugs, researchers are revisiting phage therapy to combat antibiotic-resistant infections.

When phages invade, they latch onto a bacterium and inject their genes into the cell. Once inside, they hijack the bacterium’s internal machinery and turn it into a virus factory, forcing their host to churn out new phages until the cell bursts and releases them.

To fend off these attacks, bacteria have their own tactics. The researchers were studying one such strategy — a system in the bacterium that causes cholera — when they noticed something odd. In previous work, they identified a set of genes in cholera that spot the DNA of invading phages and chop it up before the phages can take over. But interestingly, this anti-virus protection didn’t last for long.

First author Jasper Gomez conducted the work while earning his Ph.D. in the Waters lab in MSU’s department of microbiology, genetics, & immunology.

In their experiments, the researchers transferred cholera DNA encoding the protective system to E. coli, a bacterium that is easier to work with in the lab, and exposed the bacteria to phages. Before long, the engineered E. coli were under attack. In other words, the phages quickly devised a workaround to bypass their hosts’ defenses, allowing them to sneak in and hijack their victims’ cells anyway.

“Within a few hours, the phages always started to win,” Waters said. “We couldn’t understand why,” he added.

The researchers sequenced the DNA of the resistant phages and found that many had “typos” in a gene called agt, particularly in a region of repetitive DNA where the same letter, or nucleotide base, appeared multiple times in the gene sequence.

“When I saw the data, I thought, oh my gosh,” Waters said. The region resembled a type of mutational hotspot called a contingency locus. Well studied in other organisms but never shown in phages before, such regions of the genome are known to be places where the cell’s DNA copying machinery sometimes “slips” and makes mistakes, Waters said.

The result is that, each time new phages are produced, they aren’t producing exact genetic copies of their ancestor. Some of the resistant mutants gain an extra repeat unit in the agt gene, while others lose one, throwing off how the gene’s instructions are read.

The researchers found that the repetitive region accumulates mutations thousands of times faster than the rest of the genome.

While mutations are often harmful, this changeability can give phages an evolutionary edge, Waters said. By continually churning out new mutants, they increase the odds that at least some will carry a mutation that lets them evade or disarm their host’s ever-changing arsenal.

“This changes our understanding of how phages evolve,” Waters said. “Instead of hijacking their hosts to mass produce exact copies of themselves, they are actually using these mutation hotspots to make a zoo.”

Phages outnumber bacteria by around ten to one, making them the most abundant organisms on the planet. The researchers focused on a type of phage that lurks in the gut, where it specializes on E. coli bacteria, but phages can be found just about anywhere, from the sands of the Sahara Desert to the ice of the Arctic Sea.

Working with MSU microbial evolution expert Jeffrey Barrick, the team found hundreds of similar mutation hotspots scattered across the genomes of other phage species as well.

Next, the researchers are looking into whether these mutation hotspots give phages an edge in other situations, such as adapting to survive and exploit their bacterial hosts after a shift in the environment, or evolving to infect new types of bacteria.

In much of the U.S., the U.K., and elsewhere, phage therapy is still far from mainstream; regulatory hurdles make it available only as a last resort. In the meantime, Waters and other researchers at MSU are exploring potential applications beyond the clinic, to treat bacterial infections in everything from honeybees and crops to pets and livestock.

“MSU could be a great phage therapy center for veterinary and agriculture applications,” Waters said.

“We’re never going to be able to completely get rid of resistance,” he added. “But if we can better understand how bacteria protect themselves from phage infection and how phages fight back, we might be able to minimize it.”

This research was supported by grants from the U.S. National Institutes of Health (GM139537, AI158433, GM088344 and F31AI186463) and the National Science Foundation (DEB-1813069 and DEB-1951307).

CITATION: "Phage-encoded contingency loci enable bet-hedging against host defence mechanisms," Jasper B. Gomez, Jeffrey E. Barrick, Christopher M. Waters. Nature Microbiology, Aug. 13, 2026. DOI: 10.1038/s41564-026-02445-w  

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Journal

Nature Microbiology

DOI

10.1038/s41564-026-02445-w 

Method of Research

Experimental study

Subject of Research

Cells

Article Title

Phage-encoded contingency loci enable bet-hedging against host defence mechanisms

Article Publication Date

13-Aug-2026

 

A novel intervention to potentially improve the outcome of children with malnutrition

Baylor College of Medicine

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Researchers at Baylor College of Medicine and Texas Children’s Hospital have uncovered an intervention that can potentially improve the outcome of children with malnutrition, a condition that contributes to nearly half of all deaths in children under 5 years of age. The study appears in the Proceedings of the National Academy of Sciences.

“One poorly understood consequence of malnutrition is intestinal barrier erosion, which allows bacteria to escape the gut and cause invasive infections including sepsis, leading causes of mortality in malnourished children,” said study lead and co-corresponding author Dr. Geoffrey Preidis, associate professor of pediatrics – gastroenterology, hepatology and nutrition and member of the USDA/ARS Children’s Nutrition Research Center at Baylor and Texas Children's. Preidis also is co-director of the Texas Medical Center Digestive Diseases Center.

The intestinal barrier is a dynamic system that is maintained through coordinated functions of the mucus layer, the junctions between epithelial cells lining the gut and immune cells. In addition, gut microbes and products of their metabolism also play a role in regulating intestinal barrier function, but how this occurs is not well understood.

“In the current study, we investigated how the gut microbiota impacts the intestinal barrier in malnutrition and how we might leverage gut bacteria to develop new treatments to prevent sepsis and death in malnourished children,” Preidis said.

The researchers worked with a mouse model of human malnutrition. “We discovered that, just like in malnourished children, in these mice the gut barrier was damaged. The mucus layer that normally coats and protects the intestine became much thinner, and the gut became more permeable, meaning that bacteria could escape the intestines and enter the body. We found live bacteria invading the liver and spleen. Interestingly, these effects were present in male, but not female mice, similar to how malnourished boys are at higher risk of sepsis and death than malnourished girls.”

To understand whether gut bacteria were involved in damaging the gut barrier during malnutrition, the researchers applied the model of malnutrition to germ-free mice, which are raised without any microbes. Interestingly, malnutrition did not cause the same gut barrier problems in germ-free mice. This suggested that the interaction between malnutrition and the gut microbiome, rather than malnutrition alone, plays a key role in damaging the intestinal barrier.

The team also analyzed the products of gut bacterial metabolism, or metabolites, that were present in mice intestines. “One class of microbial metabolites, the branched-chain fatty acids which includes isovalerate, was depleted in malnourished mice, while these metabolites were abundant in healthy mice,” Preidis said. “This led us to identify isovalerate as a previously underappreciated microbiota-derived metabolite that supports intestinal barrier integrity.”

“We explored mechanisms by which isovalerate regulates the gut barrier using human-derived colon organoids – miniature, lab grown versions of the human gut,” Preidis said. “We discovered that isovalerate rearranges some of the proteins that make up the gut barrier and this rearrangement makes the barrier stronger in human organoids.” Would providing isovalerate to malnourished mice rescue gut barrier dysfunction in these animals?

“We provided isovalerate using two therapeutic approaches. One approach delivered isovalerate directly into the colon with enemas. In the second approach, we fed the mice leucine, an amino acid that gut bacteria convert into isovalerate,” Preidis said. “Both strategies improved gut barrier function in malnourished mice.”

Although the research was conducted mainly in mice and future studies will be needed to see whether this approach works in malnourished children, the results point toward a promising new strategy for improving outcomes in child malnutrition.

“We are excited about the possibility of developing a novel treatment for gut barrier damage in malnutrition based on leucine,” Preidis said. “Leucine costs pennies per dose, does not require refrigeration and is well-tolerated by mouth. Administering leucine as a prebiotic can allow the gut microbiota to produce isovalerate in the intestine, right where it is needed.”

“This is an impactful study and I was delighted that human colon organoids validated results from mouse models and provided new insight that isovalerate enhances barrier function by modulating tight junction processes,” said co-corresponding author Dr. Mary K. Estes, Distinguished Service Professor and Cullen Foundation Endowed Chair of molecular virology and microbiology at Baylor. Estes also is the co-director of the Gastrointestinal Experimental Model Systems core at the Texas Medical Center Digestive Diseases Center and a member of Baylor’s Dan L Duncan Comprehensive Cancer Center.

Other contributors to this work include Lauren E. Lynch, Krishnakant G. Soni, Jennifer K. Spinler, Chandra Shekar R. Ambati, Nagireddy Putluri, Stephanie W. Fowler, Margaret E. Conner, Hoa Nguyen-Phu, Xi-Lei Zeng and Sarah E. Blutt. The authors are affiliated with Baylor College of Medicine and/or Texas Children’s Hospital.

For a complete list of financial support for this work, see the publication.

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Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2611392123 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Microbiota-derived isovalerate ameliorates sex-specific gut barrier dysfunction in malnutrition

Article Publication Date

11-Aug-2026