Publisher Health

Obesity has increased rapidly in recent decades to affect more than 2 billion people, making it one of the largest contributors to poor health worldwide. Despite decades of research on diet and exercise treatments, many people continue to struggle to lose weight. Researchers at Baylor College of Medicine and collaborating institutions now think they know why, and say we must shift the focus from obesity treatment to prevention.
The team reports in the journal Science Advances that molecular mechanisms of brain development during early life are likely a major determinant of obesity risk. Previous large studies in humans have hinted that genes that are most strongly associated with obesity are expressed in the developing brain. This current study in mice focused on epigenetic development. Epigenetics is a system of molecular bookmarking that determines which genes will, or will not, be used in different cell types.
“Decades of research in humans and animal models have shown that environmental influences during critical periods of development have a major long-term impact on health and disease,” said corresponding author Dr. Robert Waterland, professor of pediatrics-nutrition and a member of the USDA Children’s Nutrition Research Center at Baylor. “Body weight regulation is very sensitive to such ‘developmental programming,’ but exactly how this works remains unknown.”
“In this study we focused on a brain region called the arcuate nucleus of the hypothalamus, which is a master regulator of food intake, physical activity and metabolism,” said first author Dr. Harry MacKay, who was a postdoctoral associate in the Waterland lab while working on the project. “We discovered that the arcuate nucleus undergoes extensive epigenetic maturation during early postnatal life. This period is also exquisitely sensitive to developmental programming of body weight regulation, suggesting that these effects could be a consequence of dysregulated epigenetic maturation.”
The team conducted genome-wide analyses of both DNA methylation — an important epigenetic tag — and gene expression, both before and after closure of the postnatal critical window for developmental programming of body weight. “One of our study’s biggest strengths is that we studied the two major classes of brain cells, neurons and glia,” MacKays said. “It turns out that epigenetic maturation is very different between these two cell types.”
“Our study is the first to compare this epigenetic development in males and females,” Waterland said. “We were surprised to find extensive sex differences. In fact, in terms of these postnatal epigenetic changes, males and females are more different than they are similar. And, many of the changes occurred earlier in females than in males, indicating that females are precocious in this regard.”
The human connection
The biggest surprise came when the investigators compared their epigenetic data in mice to human data from large genome-wide association studies that screen for genetic variants associated with obesity. The genomic regions targeted for epigenetic maturation in the mouse arcuate nucleus overlapped strongly with human genomic regions associated with body mass index, an index of obesity.
“These associations suggest that obesity risk in humans is determined in part by epigenetic development in the arcuate nucleus,” MacKay said. “Our results provide new evidence that developmental epigenetics is likely involved in both early environmental and genetic influences on obesity risk. Accordingly, prevention efforts targeting these developmental processes could be the key to stopping the worldwide obesity epidemic.”
Other contributors to this work include Chathura J. Gunasekara, Kit-Yi Yam, Dollada Srisai, Hari Krishna Yalamanchili, Yumei Li, Rui Chen and Cristian Coarfa. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Vanderbilt University, Jan and Dan Duncan Neurological Research Institute atTexas Children’s Hospital and Baylor’s Dan L Duncan Comprehensive Cancer Center.
This work was supported by grants from the USDA (CRIS 3092-5-001-059), the NIH (5R01DK111831, S10OD023469, CA125123 and 1159 RR024574), NIEHS (P30 ES030285) and CPRIT (CPRIT-RP180672).
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Materials provided by Baylor College of Medicine. Original written by Homa Shalchi. Note: Content may be edited for style and length.

Supporting emotional connection between a premature baby and mother during the intensive care unit treatment effectively improves the baby’s brain development. The effects are clearly visible in the baby’s brain network function and later neurocognitive development.
A joint study by the University of Helsinki and Columbia University showed that supporting emotional connection between mother and her premature baby following birth in the hospital intensive care unit improves the baby’s brain development.
Columbia University Professors Martha G. Welch and Michael M. Myers had previously discovered that supporting the emotional connection between mother and infant during neonatal intensive care significantly improved later neurobehavioral development.
In the current study, the brain network functions of premature infants were measured at term age, following approximately 6 weeks of Family Nurture Intervention (FNI) in the neonatal intensive care unit. All babies received normal high-standard premature care, but some families were given additional FNI to strengthen mother-infant emotional connection.
The study shows that such parental support during the intensive care treatment removed the developmental abnormalities in brain function that are typically seen in the prematurely born infants. The brain network function of the premature infants in the treatment group were not different from their control peers that were born at the normal term age.
“Treatment of premature babies in the intensive care unit has improved enormously, but supporting brain development is still a global challenge. Along with treatment innovations, better methods are needed to measure how the new treatments directly affect the developing child’s brain,” says Professor Sampsa Vanhatalo, who led the research.
New research methods facilitate care innovations by measuring the direct brain effect of novel treatments
“The new analysis methods for infant’s brain function showed that FNI affected development of the baby’s brain networks such that by term age they closely matched those of a full-term control group. And most importantly, we found that these changes also link to better neurocognitive development at 18 months,” says PhD researcher Pauliina Yrjölä, who carried out the computational analyses.
“The current research also shows how important it is to combine long-term technical research and development with innovative development of clinical treatments. In Helsinki, pioneering neuroscience work has been carried out for two decades to improve the assessment of infant brain function, while in New York exceptionally interesting non-pharmacological research on the treatment of premature infants has been carried out. The results open up a lot of perspectives both in the field of neuroscience research and clinical treatment,” says Dr. Anton Tokariev, who was responsible for the technical development.
In recent years, several studies have introduced various approaches to “enrich” the infant’s environment in the neonatal intensive care using specific sensory stimuli such as music, massage or skin contact. A new study conducted now emphasizes the importance of the natural live interaction between parent and child. The research shows that supporting the emotional connection between mother and infant leads to direct improvements in the brain activity networks, the foundation of lifelong neurocognitive performance.
“From a global point of view, the new findings are particularly interesting because this kind of treatment advance makes the intervention accessible to everyone, regardless of the resources of the healthcare system or the individual patient,” Professor Vanhatalo concludes.
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One reason that it’s so difficult to deliver large protein drugs orally is that these drugs can’t pass through the mucus barrier that lines the digestive tract. This means that insulin and most other “biologic drugs” — drugs consisting of proteins or nucleic acids — have to be injected or administered in a hospital.
A new drug capsule developed at MIT may one day be able to replace those injections. The capsule has a robotic cap that spins and tunnels through the mucus barrier when it reaches the small intestine, allowing drugs carried by the capsule to pass into cells lining the intestine.
“By displacing the mucus, we can maximize the dispersion of the drug within a local area and enhance the absorption of both small molecules and macromolecules,” says Giovanni Traverso, the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital.
In a study appearing today in Science Robotics, the researchers demonstrated that they could use this approach to deliver insulin as well as vancomycin, an antibiotic peptide that currently has to be injected.
Shriya Srinivasan, a research affiliate at MIT’s Koch Institute for Integrative Cancer Research and a junior fellow at the Society of Fellows at Harvard University, is the lead author of the study.
Tunneling through
For several years, Traverso’s lab has been developing strategies to deliver protein drugs such as insulin orally. This is a difficult task because protein drugs tend to be broken down in acidic environment of the digestive tract, and they also have difficulty penetrating the mucus barrier that lines the tract.

Dogs can smell stress from human sweat and breath, a new study by Queen’s University Belfast researchers has found.
The study involved four dogs from Belfast — Treo, Fingal, Soot and Winnie — and 36 people.
Researchers collected samples of sweat and breath from participants before and after they did a difficult maths problem. They self-reported their stress levels before and after the task and researchers only used samples where the person’s blood pressure and heart rate had increased.
The dogs were taught how to search a scent line-up and alert researchers to the correct sample. The stress and relaxed samples were then introduced but at this stage the researchers didn’t know if there was an odour difference that dogs could detect.
In every test session, each dog was given one person’s relaxed and stressed samples, taken only four minutes apart. All of the dogs were able to correctly alert the researchers to each person’s stress sample.
Clara Wilson, a PhD student in the School of Psychology at Queen’s, explains: “The findings show that we, as humans, produce different smells through our sweat and breath when we are stressed and dogs can tell this apart from our smell when relaxed — even if it is someone they do not know.
“The research highlights that dogs do not need visual or audio cues to pick up on human stress. This is the first study of its kind and it provides evidence that dogs can smell stress from breath and sweat alone, which could be useful when training service dogs and therapy dogs.
“It also helps to shed more light on the human-dog relationship and adds to our understanding of how dogs may interpret and interact with human psychological states.”
One of the super sniffer canines that took part in the study was Treo, a two-year old Cocker Spaniel. His owner Helen Parks says: “As the owner of a dog that thrives on sniffing, we were delighted and curious to see Treo take part in the study. We couldn’t wait to hear the results each week when we collected him. He was always so excited to see the researchers at Queen’s and could find his own way to the laboratory.
“The study made us more aware of a dog’s ability to use their nose to “see” the world. We believe this study really developed Treo’s ability to sense a change in emotion at home. The study reinforced for us that dogs are highly sensitive and intuitive animals and there is immense value in using what they do best — sniffing!”
The research findings have been published in PLOS ONE. The study was carried out by Clara Wilson (PhD researcher) and Kerry Campbell (MSc student) in the School of Psychology. They were supervised by Catherine Reeve, with support on collecting the human physiological measures from Zachary Petzel.
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Disruptions in circadian rhythm — the ways that our bodies change in response to the 24-hour light and dark cycle — have been linked to many different diseases, including cancer. The connection between the two has been poorly understood, even though shift workers and others with irregular schedules experience these disruptions regularly. But a new discovery from Scripps Research is helping answer what may be behind this correlation.
Published in Science Advances on September 28, 2022, the findings highlight that chronic circadian disruption significantly increased lung cancer growth in animal models. By identifying the genes implicated, the researchers are illuminating the mysterious link between our sleeping patterns and disease, which could help inform everything from developing more targeted cancer treatments to better monitoring high-risk groups.
“There has always been a lot of evidence that shift workers and others with disrupted sleep schedules have higher rates of cancer, and our mission for this study was to figure out why,” says senior author Katja Lamia, PhD, associate professor in the Department of Molecular Medicine.
To answer this question, the scientists used a mouse model with expressed KRAS — the most commonly mutated gene in lung cancer. Half of the mice were housed in a “normal” light cycle, meaning 12 hours of light and 12 hours of darkness. The other half were housed in a light cycle meant to resemble that of shift workers’, where the light hours were moved earlier by eight hours every two or three days.
The findings aligned with what the researchers initially thought: mice that were exposed to the irregular, shifting light patterns had an increased tumor burden of 68%.
But when they used RNA sequencing to determine the different genes involved in the cancer growth, they were surprised that a collection in the heat shock factor 1 (HSF1) family of proteins was the main culprit.
“This is not the mechanism we were expecting to find here. HSF1 has been shown to increase rates of tumor formation in several different models of cancer, but it has never been linked to circadian disruption before,” Lamia says.
HSF1 genes are responsible for making sure proteins are still made correctly even when a cell is under extreme stress — in this case, when it experiences changes in temperature. The team suspects that HSF1 activity is increased in response to circadian disruption because changes in our sleep cycles disturb the daily rhythms of our bodies’ temperature.
“Normally, our body temperature changes by one or two degrees while we’re sleeping. If shift workers don’t experience that normal drop, it could interfere with how the HSF1 pathway normally operates — and ultimately lead to more dysregulation in the body,” Lamia adds. She believes cancer cells may exploit the HSF1 pathway to their own benefit and create mutant, misfolded proteins, but says more research is needed in this area.
These findings help shape not only our understanding of how circadian rhythms impact cancer, but also potentially a preventative way of protecting more vulnerable groups who are at risk. By non-invasive monitoring of body temperature, it may be possible to optimize shift workers’ schedules and even halt this type of dysregulation that can lead to cancer.
With these discoveries in hand, the scientists are now evaluating if HSF1 signaling is required to increase tumor burden and isn’t solely just a correlation.
“Now that we know there’s a molecular link between HSF1, circadian disruption and tumor growth, it’s our job to determine how they’re all connected,” Lamia says.
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Many diseases have at their origin a protein that does not function properly. Now, a multidisciplinary research team with Texas A&M AgriLife and Texas A&M University has found a way to deliver a protein quickly, effectively and briefly to the brain, with therapeutic and scientific implications.
Potential uses for the method in the future could include repairing spinal cord injuries and a range of other localized injection applications.
“We found that we could successfully deliver a protein into mouse brains,” said Jean-Philippe Pellois, Ph.D., professor and associate head for graduate program, Department of Biochemistry and Biophysics in the Texas A&M College of Agriculture and Life Sciences. “Proteins are large molecules that don’t easily enter cells or cross cell membranes, but we’ve created a trick to achieve this.”
Both the protein and its delivery system degrade naturally after performing their role.
“We wanted to make sure we had reagents that are very gentle on the cell, that can enter cells without disrupting them and then leave without a trace,” said Pellois, who is also a researcher with Texas A&M AgriLife Research.
Pellois and his lab collaborated with the lab of Cédric Geoffroy, Ph.D., assistant professor in the Department of Neuroscience and Experimental Therapeutics in the Texas A&M School of Medicine.

A novel PET radiotracer can accurately assess the presence of a biomarker that indicates the level of tumor aggressiveness in neuroendocrine neoplasms (NENs). According to research published in the September issue of The Journal of Nuclear Medicine, the detection of the biomarker provides useful information for physicians to provide personalized care for patients with NENs and may also serve as a potential target for peptide radionuclide therapy (PRRT) for NEN patients.
NENs originate from the neuroendocrine cells and are found primarily in the gastrointestinal tract, pancreas, and lungs. The treatment for patients diagnosed with NENs ranges from indolent (causing little or no pain) to highly aggressive. Treatment is dependent upon the grade, or severity, of the disease, which makes accurate risk stratification important.
“Noninvasive tools to improve the risk stratification and guide decisions on treatment are warranted,” said Andreas Kjaer, MD, PhD, DMSc, professor at Rigshospitalet and University of Copenhagen in Denmark. “In this study, we aimed to assess for the first time whether the urokinase plasminogen activator receptor (uPAR) radiotracer would show accumulation in NENs and if that accumulation would be associated with survival rates.”
The prospective clinical phase II trial included 116 patients with NENs of all grades. Of these patients, 96 had whole body 68Ga-NOTA-AE105 uPAR PET/CT performed with evaluable lesions. Images were analyzed and the uPAR target-to-liver ratio was used to identify lesions as uPAR positive. Patients were then followed for at least one year to assess progression-free and overall survival. uPAR expression was seen in most patients with both low-grade and high-grade NENs. uPAR-positive lesions were noted in 68 percent of all patients and in 75 percent of patients with high-grade NENs. High uPAR expression was associated with a worse prognosis with regard to progression-free and overall survival.
“These findings are most encouraging as they imply that uPAR could be an attractive target for therapy both because of the availability of the target in patients with NENs and because of the possibility of specifically targeting lesions associated with poorer prognosis,” Kjaer noted. “As many neuroendocrine tumors — particularly those of higher grades — are not eligible for the currently available somatostatin PRRT, uPAR PRRT could become a viable therapeutic option for these patients.”
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Rheumatoid arthritis (RA) is an autoimmune disease that causes extensive inflammation of the joints, causing severe pain and discomfort in patients. But did you know that the disease is also commonly accompanied by neuropsychiatric complications, such as cognitive impairment and depression? Previous studies show that up to 70% of RA patients can have such cognitive disorders. These neurological symptoms are thought to be caused by neuroinflammation, which originates from systemic inflammation. However, the precise mechanisms of such cognitive impairment in RA remain unclear.
Previously, a team led by Director C. Justin LEE at the Center for Cognition and Sociality within the Institute for Basic Science (IBS) in Daejeon, South Korea, explored the hippocampus of dementia patients to better understand the overall mechanism of memory impairment. The group found that reactive astrocytes release an increased level of monoamine oxidase-B (MAO-B)-dependent gamma-aminobutyric acid (GABA), which in turn leads to neurological disorder.
MAOs, including MAO-A and MAO-B, are enzymes that catalyze the oxidation of monoamines and are bound to the outer mitochondrial membrane in cells of several organs, such as the brain and the immune system. More than 30 years ago, previous research suggested that MAO inhibitors can relieve pain and stiffness in RA patients. However, there have been no follow-up studies of these results, and further studies related to the role of MAO in RA have been generally lacking even until today.
Recently, Director Lee’s team revealed that interleukin-1β (IL-1β), one of these inflammatory substances that are responsible for RA, causes aberrant expression of MAO-B infibroblast-like synoviocytes cells (FLSs) isolated from joint tissues of RA patients. It was been revealed that both MAO-B and GABA are aberrantly expressed in these cells.
The team’s findings indicate that the expression of MAO-B and MAO-B products, such as GABA and H2O2, can exacerbate joint inflammation by upregulating the expression of proinflammatory factors. It was also observed that MAO-B and GABA levels were significantly increased in the RA tissue compared to the osteoarthritis (OA) tissue, which generally has a lower level of inflammation.
Notably, the researcher also observed that the RA animal model showed increased cognitive impairment. In routine behavioral experiments, normal healthy mice had no difficulty remembering a new object or location. On the other hand, it was shown that RA model mice were unable to distinguish new things and objects, which is a hallmark of a cognitive impairment disorder.
Similarly to the joint tissues, the secretion of astrocytic MAO-B-dependent GABA was aberrantly increased in the hippocampus, which is thought to be the main cause of this cognitive dysfunction. It has been known that hippocampal astrocytic MAO-B-mediated GABA inhibits neurons, causing memory and cognitive impairment. Based on the fact that astrocytes respond sensitively to inflammation, it was hypothesized that astrocytes would also be affected during the course of RA disease progression, which would lead to cognitive impairment.
The first author, Dr. WON Woojin states, “Until now, research on RA has focused only on the mechanism of inflammation, so the cause and treatment of cognitive impairment have not been clear. With a new approach of astrocytes and MAO-B, we were able to determine the cause of cognitive impairment.”
Subsequently, the IBS researchers decided to administer an MAO-B inhibitor called “KSD2010” in the RA animal model. KDS2010 is a newly developed selective and reversible MAO-B inhibitor, which is currently being tested in phase 1 clinical trials, Once administered in mice, it was discovered that both the joint inflammation decreased and cognitive function recovered at the same time.
Taken together, this study revealed both joint inflammation and cognitive impairment have a common underlying mechanism in RA patients, namely aberrant MAO-B expression. This opens the possibility of treating both of these symptoms with one drug.
“The mechanism by which cognitive impairment in RA is induced by reactive astrocytes caused by chronic inflammation was first presented. It is hoped that the newly developed and improved MAO-B inhibitor KDS2010 will become an effective next-generation treatment for RA,” explains Director C. Justin LEE, who supervised this work.

People who have had bariatric surgery may have an increased risk of developing epilepsy, according to a study published in the September 28, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“Bariatric surgery, which involves altering your digestive system, has become a more common treatment for weight loss,” said study author Jorge G. Burneo, MD, MSPH, of Western University in London, Canada, and a Fellow of the American Academy of Neurology. “While bariatric surgery is an effective treatment for obesity and obesity-related chronic conditions like high blood pressure and type 2 diabetes, our research found that bariatric surgery recipients have an elevated risk of epilepsy.”
Researchers examined health records from Ontario, Canada, to identify people who had bariatric surgery during a six-year period. After excluding people with a history of seizures, epilepsy, psychiatric disorders, or drug or alcohol abuse, they included in the study 16,958 people who had bariatric surgery. They were compared to 622,514 people with obesity who did not have bariatric surgery. Participants were followed for a minimum of three years.
A total of 73 people, or 0.4%, of those who had bariatric surgery developed epilepsy, compared to 1,260 people, or 0.2%, of those who did not have the surgery. After adjusting for other factors that could affect the risk of epilepsy, such as diabetes and high blood pressure, researchers found the estimated rates of epilepsy were 50 per 100,000 person-years among people who had bariatric surgery and 34 per 100,000 person-years among those who did not have bariatric surgery. Person-years represent both the number of people in the study and the amount of time each person spends in the study.
People who had bariatric surgery had a 45% increased risk of developing epilepsy compared to people who did not have bariatric surgery. People who had a stroke after their bariatric surgery were 14 times more likely to develop epilepsy than those who did not have a stroke.
“When considering having bariatric surgery, people should talk to their doctors about the benefits and risks,” Burneo said. “While there are many health benefits of weight loss, our findings suggest that epilepsy is a long-term risk of bariatric surgery for weight loss. Future research should investigate epilepsy as a potential long-term complication of bariatric surgery, exploring the possible effects of this procedure.”
A limitation of the study is that researchers were unable to measure obesity status or body mass index (BMI) throughout the study and researchers say some obesity-related conditions could affect epilepsy risk.
The study was supported by the Ontario Ministry of Health and Ministry of Long-Term Care and Western University.
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Air pollution has been widely associated with an increased risk of stroke. A new study looks at the role of air pollution on the trajectory of stroke, including cardiovascular events after first stroke and death. The study is published in the September 28, 2022, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“We found that high levels of air pollution were associated with increased risks of transitions from being healthy to a first stroke, cardiovascular events after stroke and death, but with a stronger effect on the transition from being healthy to having a stroke,” said study author Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health in Guangzhou, China. “These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke.”
The study involved 318,752 people in the UK biobank database with an average age of 56. The participants did not have a history of stroke or heart disease at the start of the study. Researchers looked at people’s exposure to air pollution based on where they lived at the start of the study. The participants were followed for an average of 12 years.
During that time, 5,967 people had a stroke. Of those, 2,985 people developed cardiovascular diseases and 1,020 people later died.
People exposed to high levels of air pollution were more likely to have a first stroke, post-stroke cardiovascular disease or death than people not exposed to high levels of pollution.
After adjusting for other factors that could play a role, such as smoking and physical activity level, researchers found that for each 5 micrograms per cubic meter (µg/m3) increase of fine particulate matter, for example, the risk of transitioning from being healthy to having a first stroke increased by 24% and from being healthy to dying the risk increased by30%. Particulate matter consists of liquids or solids suspended in air. Fine particulate matter, PM2.5, is less than 2.5 microns in diameter and includes fly ash from coal combustion. Those who had a stroke during the study had an average exposure of 10.03 µg/m3 of PM2.5, compared to 9.97 µg/m3 for those who did not have a stroke.
The researchers also found that the pollutants nitrogen oxide and nitrogen dioxide were associated with an increased risk of stroke and death.
“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Lin said. “People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter and using air purifiers.”
Lin noted that the results do not prove that air pollution causes stroke, cardiovascular disease or death, they only show an association.
A limitation of the study was that air pollution exposure was assessed only at the beginning of the study and only based on where participants lived.
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