Publisher Health

A new study by researchers at The Ohio State University Comprehensive Cancer Center — Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC — James) suggests a way to re-energize critical killer immune cells that have become exhausted when fighting cancer or chronic viral infections.
Immune cells called CD8 T cells are critically important in the immune system’s efforts to eliminate cancer cells and viral infected cells from the body. These cells are also key players in immune therapies called immune checkpoint blockade and CAR T-cell therapy.
For this animal and cell study, researchers first developed a new model system to study human CD8 T-cell dysfunction and whether the dysfunction can be reversed.
The work revealed that chronic signaling by transforming growth factor beta 1 (TGFβ1) accelerates the killer cells’ loss of function. It also showed that boosting the activity of a cytokine called bone morphogenetic protein 4 (BMP4) while blocking TGFβ1 could preserve the function of chronically stimulated human CD8 T cells. This also improved responses in animal models to tumors and to a chronic viral infection.
The researchers report their findings in the journal Nature Immunology.
“When killer T cells become severely dysfunctional, they are unable to effectively clear cancer or viral infections from the body, and they do not respond well to immunotherapies,” said principal investigator Hazem Ghoneim, assistant professor in the Department of Microbial Infection and Immunity.

“We found that rebalancing TGFβ1 and BMP signaling can unleash these dysfunctional T cells and enhance their response to T cell-based immunotherapies and other immune checkpoint therapies,” said Ghoneim, who is also a member of OSUCCC — James Cancer Biology Research Program.
“This novel strategy could potentially improve the effectiveness of these therapies and help to clear chronic infections or tumors more effectively,” he added.
Ghoneim and his colleagues reasoned that cues in the tumor microenvironment likely triggered the shift of T cells to a pathway leading to dysfunction. They also reasoned that identifying the key signals involved in that shift would reveal new targets that could improve the effectiveness of T-cell immune therapies.
Constant exposure to cancer-cell antigens in the tumor microenvironment causes killer T cells to show signs of mild burnout and to become mildly dysfunctional. The researchers found that these mildly dysfunctional T cells are driven to a state of profound dysfunction by chronic exposure to TGFβ1 that remain stable even after resting the cells.
They also found that the cytokine BMP4 limits the exhaustion and improves the survival of chronically stimulated CD8 T cells.
The researchers then used animal models to show that adjusting the balance of TGFβ1 and BMP signaling could: Maintain the tumor-killing ability of human CD8 T cells; Boost exhausted T-cell responses to an immune checkpoint blockage therapy; and Control a lifelong chronic lymphocytic choriomeningitis viral infection.”Our findings,” Ghoneim said, “indicate that relative levels of TGF beta and bone morphogenetic protein in a tumor microenvironment strongly influence the function of chronically stimulated CD8 T cells, revealing a potential new strategy to epigenetically reprogram dysfunctional T cells during immune checkpoint blockade therapy.”
Funding: this study was supported by startup funding from by the Ohio State University Comprehensive Cancer Center and College of Medicine.
Other Ohio State researchers involved in this study were Abbey A. Saadey, Amir Yousif, Nicole Osborne, Roya Shahinfar, Yu-Lin Chen, Brooke Laster, Meera Rajeev, Parker Bauman and Amy Webb.

New research findings show in detail how self-reactive T cells — white blood cells that mistakenly attack healthy instead of infected cells, thereby causing an autoimmune or an inflammatory response — are held in check by regulatory T cells.
Regulatory T cells, or Tregs, are patrolling white blood cells that help maintain law and order among the body’s sometimes overzealous disease-fighting T cells, also called CD4 effector cells, or Teffs.
New research findings show in detail how self-reactive T cells — white blood cells that mistakenly attack healthy instead of infected cells, thereby causing an autoimmune or an inflammatory response — are held in check by regulatory T cells. the researchers found.
This rapid Treg intervention reduces the size and number of Teff cells in order to appropriately manage the magnitude of the immune response. However, when Tregs are depleted or undergo loss of function, trouble can arise with the now unmanaged population of Teffs, which can cause disease by becoming self-reactive or hyperinflammatory.
The latest information on how Tregs operate to suppress activated Teff cells suggests that drug therapies might fill in cases when Tregs don’t function properly.
Research on the strategies used by Tregs to control Teff cell populations was recently conducted in the immunology labs of Ram Savan, associate professor of immunology at the University of Washington School of Medicine, and Steven F. Ziegler of the Benaroya Research Institute in Seattle. The lead authors were Lomon So and Kazushige Obata-Ninomiya.

Their team used a new technique, called SPEED, to detect changes in Teff protein production that could not be discovered using traditional methods
Their findings are published in the Journal of Experimental Medicine.
The scientists explained that the thymus, where T cells develop, usually recognizes, and filters out, self-reactive T cells. However, as this is not a perfect process, some self-reactive T cells escape to another location in the body. If they are not subdued, they have the potential to multiply and cause autoimmunity and inflammatory disease.
In healthy humans, cell signaling pathways increase when Teffs are activated by the presence of pathogens. These signals coordinate the growth and proliferation of the white blood cells to fight the invading pathogen and keep the host healthy.
As a countermeasure to ensure Teffs do not cause rampant inflammation or autoimmunity, Tregs produce a combination of two cytokines, Interleukin 10 (IL-10) and translational growth factor beta (TGFb), to disrupt mTORC1 signaling in activated Teff cells. This blockade in turn inhibits the translation of certain messenger RNAs. Translation is a cellular activity where mRNA is decoded into a series of amino acids to form proteins.

Tregs suppress the translation of messenger RNAs that contain a specific motif. When these messenger RNAs are blocked, the Teff cell has difficulty making fresh proteins. Therefore, by actively controlling messenger RNA translation in Teff cells, Treg cells can turn down the protein machinery that was preparing to run in high gear. Tregs thereby de-activate the stimulated Teff cells to manage the inflammatory response and keep it within appropriate bounds.
“This is a highly efficient mode of regulation: inhibiting the ramp up of biosynthesis that proceeds cell division,” the scientists noted. “It stops proliferation before it starts.” It is also a novel way, they said, for inducing and maintaining immune tolerance to avoid an autoimmune response.
When the body has an acute loss of regulatory T cells, Teff cells exhibit a fast and aberrant increase protein synthesis, in an effort to stock up their protein biomass in preparation for cell division.
In that case, the researchers learned that they could directly tamp down protein synthesis in Teff cells by using a small molecule inhibitor called rocaglamide A, or RocA. This chemical was first isolated in China in 1982 from a plant called Large-leaved Aglaia. The chemical has already been shown by several other labs to have a variety of properties against insects, fungus and cancer.
The experiments conducted in the Savan and Ziegler labs suggest that RocA might also have other therapeutic benefits, the researchers noted, by mitigating the unwanted inflammatory response that occurs from CD4 Teff cell activation. Like Treg cells, the chemical RocA suppressed protein synthesis through control of RNA translation.

DNA can signal the presence of or predisposition to a slew of diseases, including cancer. The ability to flag down these clues, known as biomarkers, allows medical professionals to make critical early diagnoses and provide personalized treatments. The typical methods of screening can be laborious, expensive or limited in what they can uncover. A new biosensor chip that boasts an accurate and inexpensive design may increase accessibility to high-quality diagnostics.
The biosensor, developed by researchers at the National Institute of Standards and Technology (NIST), Brown University and the French government-funded research institute CEA-Leti, identifies biomarkers by measuring how binding occurs between DNA strands and the device. What sets it apart from other similar sensors is its modular design, which lowers costs by making it easier to mass produce and allowing the most expensive components to be reused.
In a paper from the latest IEEE International Electron Devices Meeting just posted online, the researchers presented results of a study that demonstrates the device’s high sensitivity and precision despite its modularity, which is typically associated with diminished performance.
Like other DNA biosensors, the device takes advantage of the fact that a single DNA strand, when not paired with another within the familiar double helix, is primed for chemical bonding. Part of the device is coated with single strands of DNA. When these “probes” encounter DNA biomarkers that have a corresponding, or complementary, genetic sequence, the two strands bind, sending a signal that is picked up by the device.
“To make the measurement, we need two DNA molecules. We place one strand on our sensor that is complementary to the target DNA, that’s the proverbial needle in the haystack,” said NIST researcher Arvind Balijepalli, a co-author of the new study.
When a strand of target DNA binds to a probe, it induces a voltage shift that a semiconductor device, called a field-effect transistor (FET), can measure. These voltage shifts can occur hundreds of times a second as the molecules pop on and off the sensor.

Because of its high time resolution, this approach can tell you not only whether a DNA strand is bound to a probe, but how long it takes to connect and disconnect — a factor called binding kinetics that is key for discerning different markers that may bind to the same probe to varying degrees.
And with this method, you don’t need much space to measure a lot.
“This is a very scalable technique. In principle, we can have hundreds if not thousands of sensors in an area of one square millimeter integrated into a device the size of a smartphone, which is much less cumbersome than some of the technology currently used in the clinic,” Balijepalli said.
FET-based methods have yet to hit the mainstream, however. A significant stumbling block is their single-use nature, which until now has seemed a necessity but increases their cost.
Similar to how your radio becomes increasingly noisy as you drive away from a radio station, electrical signals also get noisier the longer they have to travel within electronics. The unwanted random noise picked up along the way makes the signal harder to measure.

To limit noise, DNA probes in FET-based sensors are normally attached to the transistor directly, which converts the signal into readable data. The drawback is that the probes are spent after being exposed to a sample, and thus the whole device is as well.
In the new study, Balijepalli and his colleagues increased the distance between the probes and the transistor so that the more expensive elements of the circuitry could be reused. The upfront penalty was that the distance could increase the amount of noise; however, there was much to be gained from the design choice, even beyond the cost savings.
“If the reader is reusable, we can build more sophisticated technology into it and get higher precision out of the readings, and it can interface with the inexpensive and disposable sensing element,” Balijepalli said.
Because they anticipated that the modular design would diminish the biosensor’s sensitivity, the researchers took a page out of the Internet of Things (IoT) playbook, which accommodates the losses associated with wireless devices. The NIST authors paired their circuitry with a specific type of extremely low-power FET developed at CEA-LETI that is used in smartwatches, personal assistants and other devices to amplify signals and compensate for the lost sensitivity.
To test the performance of their device, they placed it in liquid samples containing DNA strands associated with exposure to harmful ionizing radiation. Complementary DNA probes adorned electrodes wired to the FET. Across several samples, they varied the amount of target DNA.
The researchers found that the binding kinetics were sensitive enough to make accurate measurements even at low concentrations. Overall, the performance of the modular design matched that of integrated, nonmodular FET-based biosensors.
The next step in their research is to find out if their sensor can perform similarly with varying DNA sequences caused by mutations. Since many diseases are caused by or associated with mutated DNA, this capability is essential for clinical diagnostics.
Other studies may evaluate the sensor’s ability to detect genetic material associated with viruses, such as COVID-19, that could hint at infection.
In the meantime, the new technology could represent a viable foundation to build upon.
“There’s an opportunity to develop more sophisticated modular sensors that are much more accessible without sacrificing high quality measurements,” Balijepalli said.

A soldier suffers a serious gunshot wound on a remote battlefield or a machinist has a work accident and gets stuck in traffic on the way to the hospital. Secondary, uncontrolled bleeding from traumatic injury is the leading cause of death of Americans from ages one to 46.
Amir Sheikhi, assistant professor of chemical engineering and of biomedical engineering at Penn State, has a plan to change that with a novel microneedle patch that can immediately stop bleeding after injury.
He laid out his prototype in a new paper that will be published in the May issue of Bioactive Materials, available now online.
“Excessive bleeding is a serious challenge for human health,” Sheikhi said. “With hemorrhaging injuries, it is often the loss of blood — not the injury itself — that causes death. There is an unmet medical need for ready-to-use biomaterials that promote rapid blood coagulation.”
The hemostatic microneedle technology developed by Sheikhi can be applied like a typical adhesive bandage to quickly stop bleeding. The biocompatible and biodegradable microneedle arrays (MNAs) on the patch increase its surface contact with blood and accelerate the clotting process. The needles also increase the adhesive properties of the patch via mechanical interlocking to promote wound closure.
“In vitro, the engineered MNAs reduced clotting time from 11.5 minutes to 1.3 minutes; and in a rat liver bleeding model, they reduced bleeding by more than 90%,” Sheikhi said. “Those 10 minutes could be the difference between life and death.”
The MNA patch can be compared with the hydrogel technology that is currently used to treat bleeding wounds in hospitals, but hydrogel applications require preparation and medical expertise. The microneedle patch is pre-engineered for immediate application that anyone can use to stop bleeding, Sheikhi said, much like a typical over-the-counter adhesive bandage.
Microneedles — which are already in use to deliver biologics, such as cells or drugs, through the skin or for cosmetic procedures to stimulate collagen production — are tiny, making their application pain-free, according to Sheikhi.
The researchers are now working to translate the patch from the lab to the market, with plans to further test the technology.
All the animal experiments were carried out after the approval of animal protocol by the UCLA Animal Research Committee. Animal handling procedures were performed following the “Guide for the Care of Laboratory Animals.”
Sheikhi received financial support from the Canadian Institutes of Health Research through a postdoctoral fellowship as well as the startup fund from The Pennsylvania State University.
Sheikhi started this work as a postdoctoral scholar at the University of California, Los Angeles, in the lab of Ali Khademhosseini, now the chief executive officer of Terasaki Institute for Biomedical Innovation (TIBI). Other UCLA contributors include Reihaneh Haghniaz, Hossein Montazerian, Avijit Baidya, Maryam Tavafoghi and Yi Chen. Han-Jun Kim, Yangzhi Zhu and Solmaz Karamikamkar, all formerly with the Khademhosseini Lab and now all affiliated with TIBI, also contributed.

A new Cedars-Sinai study suggests that some patients diagnosed with behavioral-variant frontotemporal dementia (bvFTD) — an incurable condition that robs patients of the ability to control their behavior and cope with daily living — may instead have a cerebrospinal fluid leak, which is often treatable.
Researchers say these findings, published in the peer-reviewed journal Alzheimer’s & Dementia: Translational Research and Clinical Interventions, may point the way to a cure.
“Many of these patients experience cognitive, behavioral and personality changes so severe that they are arrested or placed in nursing homes,” said Wouter Schievink, MD, director of the Cerebrospinal Fluid Leak and Microvascular Neurosurgery Program and professor of Neurosurgery at Cedars-Sinai. “If they have behavioral-variant frontotemporal dementia with an unknown cause, then no treatment is available. But our study shows that patients with cerebrospinal fluid leaks can be cured if we can find the source of the leak.”
Cerebrospinal fluid (CSF) circulates in and around the brain and spinal cord to help cushion them from injury. When this fluid leaks into the body, the brain can sag, causing dementia symptoms. Schievink said many patients with brain sagging — which can be detected through MRI — go undiagnosed, and he advises clinicians to take a second look at patients with telltale symptoms.
“A knowledgeable radiologist, neurosurgeon or neurologist should check the patient’s MRI again to make sure there is no evidence for brain sagging,” Schievink said.
Clinicians can also ask about a history of severe headaches that improve when the patient lies down, significant sleepiness even after adequate nighttime sleep, and whether the patient has ever been diagnosed with a Chiari brain malformation, a condition in which brain tissue extends into the spinal canal. Brain sagging, Schievink said, is often mistaken for a Chiari malformation.
Even when brain sagging is detected, the source of a CSF leak can be difficult to locate. When the fluid leaks through a tear or cyst in the surrounding membrane, it is visible on CT myelogram imaging with the aid of contrast medium.
Schievink and his team recently discovered an additional cause of CSF leak: the CSF-venous fistula. In these cases, the fluid leaks into a vein, making it difficult to see on a routine CT myelogram. To detect these leaks, technicians must use a specialized CT scan and observe the contrast medium in motion as it flows through the cerebrospinal fluid.
In this study, investigators used this imaging technique on 21 patients with brain sagging and symptoms of bvFTD, and they discovered CSF-venous fistulas in nine of those patients. All nine patients had their fistulas surgically closed, and their brain sagging and accompanying symptoms were completely reversed.
“This is a rapidly evolving field of study, and advances in imaging technology have greatly improved our ability to detect sources of CSF leak, especially CSF-venous fistula,” said Keith L. Black, MD, chair of the department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai. “This specialized imaging is not widely available, and this study suggests the need for further research to improve detection and cure rates for patients.”
The remaining 12 study participants, whose leaks could not be identified, were treated with nontargeted therapies designed to relieve brain sagging, such as implantable systems for infusing the patient with CSF. However, only three of these patients experienced relief from their symptoms.
“Great efforts need to be made to improve the detection rate of CSF leak in these patients,” Schievink said. “We have developed nontargeted treatments for patients where no leak can be detected, but as our study shows, these treatments are much less effective than targeted, surgical correction of the leak.”

About 13,200 men and another 2,300 women in the United States over age 50 are estimated to have VEXAS syndrome, according to a new study. Long considered a mystery illness until its genetic basis was identified in 2020, the latest findings, led by researchers at NYU Grossman School of Medicine, offer the first indication of how common the illness is domestically.
Although a rare disorder, the syndrome carries a high mortality rate, with up to half of people, mostly men, dying within five years of diagnosis. The syndrome most often involves unexplained fevers and low blood oxygen levels in people diagnosed with other diseases, such as rheumatoid arthritis, lupus, and blood cancer. Some of the symptoms have been linked to an overactive immune system, which can cause inflammation and classifies the syndrome as an autoimmune condition.
Researchers say they hope their findings will raise awareness of the disorder among physicians, particularly because high-dose steroids, JANUS kinase inhibitors, and bone marrow transplantation have proven effective in controlling some symptoms.
“Now that we know VEXAS syndrome is more common than many other types of rheumatologic conditions, physicians need to add this condition to their list of potential diagnoses when confronted by patients with persistent and unexplained inflammation and low blood cell counts, or anemia,” says geneticist and study lead investigator David Beck, MD, PhD. Beck, an assistant professor in the Department of Medicine and the Department of Biochemistry and Molecular Pharmacology at NYU Langone Health, also led the federal research team that initially identified the shared UBA1 mutation among VEXAS patients.
In the new study, publishing in the Journal of the American Medical Association (JAMA) online Jan. 24, researchers analyzed the electronic health records of 163,096 mostly white men and women in Pennsylvania who agreed to have their blood DNA screened for signs of genetic disease. Twelve were found to have the UBA1 mutation, with all experiencing VEXAS symptoms.
Statistically, this corresponded to one in 4,269 American men over age 50 and one in 26,238 women over age 50 having or are likely to develop the syndrome. This, researchers say, is a higher prevalence figure than many other inflammatory conditions, including vasculitis and myeloid dysplasia syndrome.

“Our study offers the first glimpse of just how common VEXAS syndrome is in the United States, particularly among men, who also happen to be the most to die from it,” says Beck, who is leading several clinical research efforts into VEXAS syndrome at NYU Langone’s Center for Human Genetics and Genomics.
Previous research, led by Beck, traced the origins of the syndrome to a mutation, or change in the letter code that makes up DNA, in the gene UBA1 (short for ubiquitin-like modifier activating enzyme 1.) The enzyme usually assists in protein breakdown.
VEXAS stands for many of its biological characteristics: vacuoles in blood cells, the E1 enzyme, X-linked, autoinflammatory, and somatic.
For the study, researchers analyzed the electronic medical records of adult patients who volunteered to participate in the Geisinger MyCode Community Health Initiative. The program has been collecting data for more than 25 years from patients in Geisinger’s 10-plus hospitals in Central and Northeastern Pennsylvania. Almost all study participants who agreed to have their blood DNA tested were white; half were over the age of 60.
Beck says the team next plans to analyze patient records in more racially diverse groups, especially among those with higher rates of rheumatologic and blood disease, to gain a more precise picture of who is most at risk of VEXAS syndrome. They also plan to look for additional genetic causes, test new therapies for the syndrome, and develop a simple blood test for UBA1 to make it easier to diagnose.
Funding for the study was provided by National Institute of Health grants R00AR078205 and T32GM136542.
Besides Beck, other NYU Langone researchers involved in this study are Samuel Magaziner, MPhil; and Ann Cantor, MS. Other study co-investigators are Dale Bodian, PhD, at Geisinger Research in North Bethesda, Md.; Vandan Shah, MD; Uyenlinh Mirshahi, PhD; Natasha Strande PhD; Jeremy Haley, MS; Adam Cook, MS; Wesley Hill; Yi Ding, MD, PhD; and David Carey, PhD, at Geisinger Health in Danville, Pa.; Jung Kim, PhD, and Douglas Stewart, at the National Cancer Institute in Rockville, Md.; Alan Schwartz, MD, PhD, at the University of Washington in St. Louis, Mo.; Peter Grayson, MD, and Marcela Ferrada, MD, at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda; and Daniel Kastner, MD, at the National Human Genome Research Institute, also in Bethesda.

Cells zealously protect the integrity of their genomes, because damage can lead to cancer or cell death. The genome — a cell’s complete set of DNA — is most vulnerable while it is being duplicated before a cell divides. Cancer cells constantly are dividing, so their genomes are constantly in jeopardy.
Researchers at Washington University School of Medicine in St. Louis have identified a previously unknown signaling pathway cells use to protect their DNA while it is being copied. The findings, published Jan. 24 in the journal Molecular Cell, suggest that targeting this pathway potentially could boost the potency of cancer therapeutics.
“A cell that can’t protect its genome is going to die,” said senior author Zhongsheng You, PhD, a professor of cell biology & physiology. “This entire pathway we found exists to protect the genome so the cell can survive in the face of replication stress. By combining inhibitors of this pathway with chemotherapy drugs that target the DNA replication process, we potentially could make such drugs more effective.”
Replication stress occurs when the cell’s DNA duplication machinery runs into problems copying the genome. Certain stretches of DNA are inherently difficult to copy, because they contain many repeated sequences. Factors that damage the DNA, such as radiation and toxic molecules, also cause replication stress, as does the activation of cancer-causing genes. Dozens of cancer drugs, including widely used medications such as cisplatin and doxorubicin, work by damaging the DNA and increasing replication stress.
You studies how cells protect their genomes while they are being duplicated. Early in his career, he worked on the ATR-Chk1 genome-protection pathway — a pathway that controls the cell-division cycle and prevents stalled replication machinery from failing entirely and causing breaks in the DNA. For the past eight years, he and his team painstakingly have been piecing together another previously unknown genome-protection pathway. With this new study, the final piece of the puzzle has clicked into place.
The process they discovered goes like this: When the DNA-duplicating machinery stalls, a protein called Exo1 that normally follows behind the machinery gets a little out of hand. Exo1’s job is to perform quality control by cutting out incorrectly copied pieces of DNA, but when the machinery stops moving forward, Exo1 starts snipping away haphazardly, cleaving off bits of DNA that then make their way out of the nucleus and into the main part of the cell. DNA is not found outside the nucleus under normal conditions, so its presence in the main part of the cell sets off an alarm. Upon encountering a fragment of DNA, a sensor molecule triggers a cascade of molecular events, including the release of the calcium ion from a cellular organelle known as the endoplasmic reticulum, which in turn shuts down Exo1, preventing it from dicing up the genome any further until the problem with the machinery can be fixed.
This newest study describes the discovery of DNA fragments as the warning signal that sets off the whole genome-protection response. The study was led by first author Shan Li, PhD, as a postdoctoral researcher and then a staff scientist in You’s lab. Li is now an assistant professor at Zhejiang University School of Medicine in Hangzhou, China. Co-author Lingzhen Kong, a graduate student, also made important contributions to the study.
Over the years, You and colleagues have identified eight protein factors involved in this genome-protection pathway. Most of them already have inhibitors under development that could be repurposed for cancer studies.
“Now that we have the pathway, we want to know whether it can be targeted for cancer treatment,” You said. “Lung, ovarian and breast cancer are intrinsically under replication stress. Other cancers are put under replication stress by chemotherapy drugs. This pathway protects cells from replication stress, so if we could block the pathway, it might improve patients’ response to cancer therapies.”
Several of the proteins in this pathway also play a role in other critical biological processes, including immunity, metabolism and autophagy, the process by which cells break down their own unwanted materials.
“One of the most exciting things about this pathway is how it intersects with so many other pathways,” You said. “I’ve been focusing on cancer, but much of this could also apply to autoimmune diseases. Two of the proteins we identified have been linked to chronic activation of the immune response and autoimmune disease. We want to understand the relationship between this replication-stress response pathway and the innate immune response pathway. The work we do is very basic, and it is so exciting to connect the dots between these fundamental processes and see how they relate to human health and disease.”

There is scientific evidence that maternal exposure to natural environments supports healthy fetal growth. However, study results up to date had been heterogeneous across regions and there is very little research on the effects of blue spaces such as rivers, the sea or lakes. A new study involving a team from the Barcelona Institute for Global Health (ISGlobal), an institution supported by “la Caixa” Foundation,” assessed the associations between maternal exposure to green and blue spaces during pregnancy and birth outcomes in 11 birth cohorts from nine European countries, including Spain.
The results of the study, published in the journal Environment International, indicate that proximity to residential green space is associated with higher birth weight and lower odds of having a small-for-gestational-age baby, or SGA, as newborns whose birth weight is less than or equal to the 10th lower percentile are called. In contrast, greater distance to residential green space is associated with lower birth weight and higher odds of SGA. The results showed almost no associations for accessibility to green spaces and exposure and accessibility to blue spaces.
“A healthy fetal growth can greatly reduce the risk of adverse health outcomes, both early and later in life,” says Maria Torres, first author of the study. “For example, babies with low birth weight or being SGA could have an increased risk of growth impairment, lower IQ and premature death in childhood, as well as obesity, cardiovascular disease and diabetes in adulthood.”
This study, part of the LifeCycle project, was based on a sample of 69,683 newborns, with an average birth weight of 3.42 kg, of whom 6.6% were classified as SGA. For each participant, seven indicators of residential exposure to natural environments were calculated: surrounding green space within 100, 300 and 500 metres of the household — calculated using the Normalised Difference Vegetation Index (NDVI)-, distance to the nearest green space, accessibility to green space, distance to the nearest blue space and accessibility to blue space.
The research team also evaluated the potential effect modification by socioeconomic status (SES) and region of Europe. The results indicate stronger associations between residential green spaces and higher birth weight for participants with lower educational levels, from more deprived areas, and residing in the Northern European region.
The results of this study are in line with previous research from various regions around the world. An increasing number of studies have reported associations between maternal exposure to green spaces and higher birth weight. However, most of these studies were conducted in a single country with a particular climate and vegetation type, and estimates of the effect differed from region to region. “Capitalising on data from 11 birth cohorts across Europe allowed us to assess, for the first time, this association in different countries and shed light on the regional role in this issue,” explains Payam Dadvand, ISGlobal researcher and senior author of the study.
The research involved people from the Netherlands, United Kingdom, Denmark, France, Spain, Lithuania, Norway, Italy and Greece. According to the authors, the results of this study could support the implementation of policies to promote natural environments in our cities, starting with the most disadvantaged areas. “Having accessible natural environments in our cities could benefit our children’s health from before birth and beyond, and this should be taken into account by urban designers,” concludes Maria Torres.

A new study by researchers at the University of British Columbia and the University of Victoria has shown that common levels of traffic pollution can impair human brain function in only a matter of hours.
The peer-reviewed findings, published in the journal Environmental Health, show that just two hours of exposure to diesel exhaust causes a decrease in the brain’s functional connectivity — a measure of how The study provides the first evidence in humans, from a controlled experiment, of altered brain network connectivity induced by air pollution.
“For many decades, scientists thought the brain may be protected from the harmful effects of air pollution,” said senior study author Dr. Chris Carlsten, professor and head of respiratory medicine and the Canada Research Chair in occupational and environmental lung disease at UBC. “This study, which is the first of its kind in the world, provides fresh evidence supporting a connection between air pollution and cognition.”
For the study, the researchers briefly exposed 25 healthy adults to diesel exhaust and filtered air at different times in a laboratory setting. Brain activity was measured before and after each exposure using functional magnetic resonance imaging (fMRI).
The researchers analyzed changes in the brain’s default mode network (DMN), a set of inter-connected brain regions that play an important role in memory and internal thought. The fMRI revealed that participants had decreased functional connectivity in widespread regions of the DMN after exposure to diesel exhaust, compared to filtered air.
“We know that altered functional connectivity in the DMN has been associated with reduced cognitive performance and symptoms of depression, so it’s concerning to see traffic pollution interrupting these same networks,” said Dr. Jodie Gawryluk, a psychology professor at the University of Victoria and the study’s first author. “While more research is needed to fully understand the functional impacts of these changes, it’s possible that they may impair people’s thinking or ability to work.”
Taking steps to protect yourself
Notably, the changes in the brain were temporary and participants’ connectivity returned to normal after the exposure. Dr. Carlsten speculated that the effects could be long lasting where exposure is continuous. He said that people should be mindful of the air they’re breathing and take appropriate steps to minimize their exposure to potentially harmful air pollutants like car exhaust.
“People may want to think twice the next time they’re stuck in traffic with the windows rolled down,” said Dr. Carlsten. “It’s important to ensure that your car’s air filter is in good working order, and if you’re walking or biking down a busy street, consider diverting to a less busy route.”
While the current study only looked at the cognitive impacts of traffic-derived pollution, Dr. Carlsten said that other products of combustion are likely a concern.
“Air pollution is now recognized as the largest environmental threat to human health and we are increasingly seeing the impacts across all major organ systems,” says Dr. Carlsten. “I expect we would see similar impacts on the brain from exposure to other air pollutants, like forest fire smoke. With the increasing incidence of neurocognitive disorders, it’s an important consideration for public health officials and policymakers.”
The study was conducted at UBC’s Air Pollution Exposure Laboratory, located at Vancouver General Hospital, which is equipped with a state-of-the-art exposure booth that can mimic what it is like to breathe a variety of air pollutants. In this study, which was carefully designed and approved for safety, the researchers used freshly-generated exhaust that was diluted and aged to reflect real-world conditions.