Culture

A new study at the University of Chicago has determined that restoring a single microbial species -- Bacteroides sp. CL1-UC (Bc) -- to the gut microbiome at a key developmental timepoint can prevent antibiotic-induced colitis in a mouse model of the condition. The results, published on June 7 in Gastroenterology, have major implications for humans dealing with inflammatory bowel disease (IBD), and underscore the impact of early childhood exposures on health throughout the lifetime.

Prior studies in human patients have found that early life exposure to antibiotics can skew the gut microbiome, causing dysbiosis, or an imbalance of the microbial populations in the gut, which is correlated with increase risk for developing pediatric IBD.

"We know that the kinds of microbes that you're exposed to early in life actually determine how your immune system develops," said senior author Eugene Chang, MD, Martin Boyer Professor of Medicine at UChicago. "Our immune system learns to recognize our own selves, and the trillions of microbes in our gut -- they're 'us' as well, so our immune system has to learn to tolerate these organisms, just as it tolerates our own cells. Early exposure to antibiotics can eradicate some of the organisms that are essential for educating the immune system to develop immune tolerance."

Due to the challenges of conducting such studies in human patients, the researchers opted to use a common model for studying colitis: mice that lack a gene known as IL-10 (IL-10-/-). "This mouse model has been established as being genetically susceptible to IBD, and we know that the gut microbiome plays a crucial role in the development of colitis in this model," said first author Jun Miyoshi, MD, PhD, a Senior Assistant Professor in the Department of Gastroenterology and Hepatology at Kyorin University School of Medicine, and a former postdoctoral scholar at UChicago.

While only very rarely do these mice develop spontaneous colitis without any intervention in a clean environment, if their mothers are exposed to antibiotics during pregnancy and nursing, the disrupted microbiome can be transmitted to the pups at an early age. Around 30% of pups with this vertically transmitted disrupted microbiome go on to develop colitis.

The investigators used a technique known as shotgun metagenomic sequencing to screen the fecal microbiomes of IL-10-/- mice that had antibiotic-induced dysbiosis, alongside an untreated control group, and identify specific microbial species that might distinguish the two groups. This led them to members of the bacterial phylum Bacteroides.

One clue of the phylum's importance was that Bacteroides was very abundant in the microbiomes of untreated mice, but completely lacking in the mice that had been exposed to antibiotics. What's more, the researchers never saw Bacteroides in the treated mice that did not go on to develop colitis -- but they often found Bacteroides in the guts of mice that did end up with the condition.

"These bacteria were eradicated by early exposure to antibiotics and were essential for educating the immune system in developing immune tolerance," said Chang. "When those mice later acquired the bacteria, their immune system had never seen it. It was viewed as foreign, not as self, and their immune systems reacted to it."

In an effort to determine whether restoring important Bacteroides back to the microbiome could correct the dysbiosis, the researchers honed in on a particularly abundant species known as Bacteroides sp. CL1-UC (Bc). They tried adding Bc back to the microbiomes of the mice with dysbiosis at two timepoints: around infancy (three weeks of age) and adulthood (11 weeks of age).

Engrafting Bc into the younger mice, during the critical immune system developmental window, corrected their dysbiosis and prevented colitis, but adding Bc back to adult mice could not correct the dysbiosis, and even worsened their colitis.

"This shows that you can't just restore the missing bacteria at any time point, it has to be at a specific time early in life to have a beneficial effect," said Chang. "In young animals, we know that the immune system is developing, it's naive, it has to be taught, and it's taught by being exposed to certain kinds of microbes. In some ways, it's similar to a peanut allergy -- early exposure to the antigen can tolerize the immune system to help avoid a peanut allergy, but it has to happen within a very finite window."

The researchers were surprised to learn that restoring a single microbe was enough to correct lifelong dysbiosis, and said it highlighted how relatively small changes can have a dramatic impact on a system. "It's like the tall trees of the Amazon rainforest," said Chang. "You need the tall trees, because if you don't have them, the ecosystem below cannot develop properly. But if you have those trees in place, the rest of the ecosystem will flourish."

The results also go against popular theories on the origin of IBD. "There's a misconception that colitis is caused by a classical pathogen, like salmonella, and scientists have spent years looking for a culprit," said Chang. "But what our data are pointing to is that these diseases are caused by our own commensal microbes. They are present in the normal, healthy microbiome, but given the right circumstance and opportunity, they can transform into disease-promoting microbes."

While this early study was proof-of-concept, if the results translate to humans, the ripple effects are likely to be far-reaching. "This shows that we probably have to rethink our approach to these kinds of complex immune disorders," said Chang. "We can see that risk is developing early in life -- even in utero -- and so this has implications for practices such as C-sections and formula feeding, which can impact the microbes an infant is exposed to. What this says to me is that, as physicians, we need to shift our thinking to not what immediately preceeds these diseases but what happens early in life. That's where we need to intervene for these patients."

TROY, N.Y. -- More strategic and coordinated travel restrictions likely could have reduced the spread of COVID-19 in the early stages of the pandemic. That's according to new research published in Communications Physics. This finding stems from new modeling conducted by a multidisciplinary team of scientists and engineers at Rensselaer Polytechnic Institute.

The researchers evaluated the distance between countries in terms of air travel, a more complex measurement than simply mapping physical distance. For instance, while China and Thailand may be geographically more proximate to one another, if there are significantly more flights between China and the United States, the chance of disease spread may be higher.

"This is considered a global problem," said Mamadou Diagne, an assistant professor of mechanical, aerospace, and nuclear engineering at Rensselaer, "so we wanted to know if coordinated action could be taken to mitigate contamination rates all across the world."

By mapping and analyzing the global mobility network through air traffic patterns, the researchers were able to determine the level of connection between various nations and develop a model that can predict which countries are closer to one another in terms of disease spread. The model was able to successfully predict when the virus arrived in the United States.

Using this approach, the team examined the effectiveness of various travel restrictions countries implemented in an effort to slow the transmission of the virus that causes COVID-19.

"For example, we found that the Chinese lockdown reduced the arrival time of the virus in uninfected countries by about 10 days," said Jianxi Gao, an assistant professor of computer science at Rensselaer. "And, it reduced the number of infections by 6 million globally."

Travel restrictions enacted by other nations, including entry bans, global travel bans, and lockdowns, also helped to reduce the global spread. However, the Rensselaer team found that these actions could have been significantly more effective had countries worked in concert with one another.

"According to the data we collected, about 63.2% percent of travel restrictions were ineffective," said Lu Zhong, a postdoctoral researcher in mechanical, aerospace, and nuclear engineering. "Because the travel restrictions were done in an uncoordinated way, they failed to contribute to the global good."

Diagne, Gao, and Zhong found that redundant or unnecessary travel restrictions also affected the global economy. A more efficient approach, they said, could mitigate economic harm.

BOSTON - Current guidelines recommend stopping cervical cancer screening at age 65, but women over age 65 make up over one in five new cervical cancer diagnoses, and are twice as likely to die after a cervical cancer diagnosis compared to younger women. New research from Boston Medical Center found that fewer than one in three women aged 64 to 66 met the criteria to discontinue cervical cancer screening while looking at patients with both private insurance and from a safety-net hospital setting. Published in Gynecologic Oncology, researchers found that even among women with 10 years of continuous insurance coverage, 41.5 percent did not qualify to end screening and most women did not receive adequate screening in the ten years leading up to this important screening decision.

The majority of women aged 65 and older may be at risk for cervical cancer due to inadequate screening or preexisting high-risk conditions. Study findings show that up to 20 percent of women reported a medical condition or a history of screening abnormalities that make this screening necessary beyond the age of 65. This highlights the need to educate patients and healthcare providers on the importance of ensuring adequate cervical cancer screening at ages 55 to 65, and also on high-risk conditions that necessitate screening beyond age 65. When data are adjusted for patient hysterectomies, the incidence of cervical cancer is highest among women ages 65 to 69 and remains elevated through age 85.

"Providers need to be aware that cervical cancer is a growing problem among women aged 65 and older, and that it is preventable," says Rebecca Perkins, MD, MPH, obstetrics & gynecology physician at BMC. "It's imperative for providers to proactively ensure that their patients receive adequate screening between the ages of 55 and 65 to decrease preventable cancers in women over the age of 65, and to make sure that their patients are adequately screened to be able to safely exit screening, if their health history qualifies."

The study data included 590,901 women aged 64 with employer-sponsored insurance enrolled in the national Truven MarketScan database between 2016 and 2018, and 1544 women aged 64 to 66 receiving primary care at a safety net health center in 2019, identified through an electronic health record query. Screening exit eligibility was determined using the current guidelines that include: no evidence of cervical cancer or HIV-positive status, no evidence of cervical pre-cancer in the past 25 years, and evidence of either a hysterectomy with removal of the cervix or evidence of fulfilling the screening exit criteria. The exit criteria are defined as two human papillomavirus (HPV) screening tests or HPV plus Pap co-tests or three Pap tests within the past 10 years without evidence of an abnormal result (screening with HPV testing or HPV/Pap co-testing provides more long term reassurance against cancer development than Pap testing alone).

Data from both the safety net hospital and national claims database indicated that fewer than half of women aged 64 to 66 had documentation of sufficient screening to fulfill the exit criteria. Guidelines specify that patients with immunosuppression, histories of abnormal results or cervical precancer, or cancer should continue screening. Current screening exit criteria are complex and require a detailed review of at least ten years of medical record documentation, which can create barriers to applying the guidelines to clinical practice.

"No patient should ever discontinue screening based on age alone without their healthcare provider completing a thorough review of their medical record," says Perkins, also an associate professor of obstetrics and gynecology at Boston University School of Medicine. "Improved cervical cancer screening in women 55 years and older may reduce cancer rates and mortality in women aged 65 and over."

Possible solutions to improve these rates include a Medicare-funded cancer prevention visit where the need for a cervical cancer screening is reviewed, and the optimization of electronic medical records to prompt a review of the cervical cancer exit screening criteria prior to a patient's screening discontinuation.

GAINESVILLE, Fla. --- A more reliable way of estimating the size of megalodon shows the extinct shark may have been bigger than previously thought, measuring up to 65 feet, nearly the length of two school buses. Earlier studies had ball-parked the massive predator at about 50 to 60 feet long.

The revised estimate is the result of new equations based on the width of megalodon's teeth - and began with a high school lesson that went awry.

Victor Perez, then a doctoral student at the Florida Museum of Natural History, was guiding students through a math exercise that used 3D-printed replicas of fossil teeth from a real megalodon and a set of commonly used equations based on tooth height to estimate the shark's size. But something was off: Students' calculations ranged from about 40 to 148 feet for the same shark. Perez snapped into trouble-shooting mode.

"I was going around, checking, like, did you use the wrong equation? Did you forget to convert your units?" said Perez, the study's lead author and now the assistant curator of paleontology at the Calvert Marine Museum in Maryland. "But it very quickly became clear that it was not the students that had made the error. It was simply that the equations were not as accurate as we had predicted."

Although the equations have been widely used by scientists since their publication in 2002, the classroom exercise revealed they generate varying size estimates for a single shark, depending on which tooth is measured.

"I was really surprised," Perez said. "I think a lot of people had seen that study and blindly accepted the equations."

For more than a century, scientists have attempted to calculate the size of megalodon, whose name means "big tooth." But the only known remains of the fearsome shark that dominated oceans from about 23 to 3.6 million years ago are fossilized teeth and a few, rare vertebrae. Like other sharks, the rest of megalodon's skeleton, including its jaw, was composed of lightweight cartilage that decomposed quickly after death. Tooth enamel, however, "preserves really well," Perez said. "It's probably the most structurally stable thing in living organisms." Megalodon sharks shed thousands of teeth over a lifetime, leaving abundant traces of the species in the fossil record.

The most accepted methods for estimating the length of megalodon have used great white sharks as a modern proxy, relying on the relationship between tooth size to total body length. While great white sharks and megalodon belong to different families, they share similar predatory lifestyles and broad, triangular teeth serrated like steak knives - ideal adaptations for hunting large, fleshy marine mammals such as whales and dolphins, Perez said.

But these methods also present a challenge: To generate body length estimates, they require the researcher to correctly identify a fossil tooth's former position in a megalodon jaw. As in humans, the size and shape of shark teeth vary depending on where they're located in the mouth, and megalodon teeth are most often found as standalone fossils.

So, Perez was ecstatic when fossil collector Gordon Hubbell donated a nearly complete set of teeth from the same megalodon shark to the Florida Museum in 2015, reducing the guesswork. After museum researchers CT scanned the teeth and made them available online, Perez collaborated with teacher Megan Higbee Hendrickson on a plan to incorporate them into her middle school curriculum at the Academy of the Holy Names school in Tampa.

"We decided to have the kids 3D-print the teeth, determine the size of the shark and build a replica of its jaw for our art show," Hendrickson said.

Perez and Hendrickson co-designed a lesson for students based on the then-most popular method for estimating shark size: Match the tooth to its position in the shark jaw, look up the corresponding equation, measure the tooth from the tip of the crown to the line where root and crown meet and plug the number into the equation.

After a successful pilot test of a few teeth with Hendrickson's students, he expanded the lesson plan to include the whole set of megalodon teeth for high school students at Delta Charter High School in Aptos, California. Perez expected a slight variability of a couple millimeters in their results, but this time, variations in students' estimates shot to more than 100 feet. The farther a tooth position was from the front of the jaw, the larger the size estimate.

After Perez detailed the lesson's results in a fossil community newsletter, he received an email from Teddy Badaut, an avocational paleontologist in France. Badaut suggested a different approach. Why not measure tooth width instead of height? Previous research had suggested tooth width was limited by the size of a shark's jaw, which would be proportional to its body length.

Ronny Maik Leder, then a postdoctoral researcher at the Florida Museum, worked with Perez to develop a new set of equations based on tooth width.

By measuring the set of teeth from Hubbell, "we could actually sum up the width of the teeth and get an even better approximation of the jaw width," Perez said.

The researchers analyzed sets of fossil teeth from 11 individual sharks, representing five species, including megalodon, its close relatives and modern great white sharks.

By measuring the combined width of each tooth in a row, they developed a model for how wide an individual tooth was in relation to the jaw for a given species. Now when a paleontologist unearths a lone megalodon tooth the size of their hand, they can compare its width to the average obtained in the study and get an accurate estimate of how big the shark was.

"I was quite surprised that indeed no one had thought of this before," said Leder, now director of the Natural History Museum in Leipzig, Germany. "The simple beauty of this method must have been too obvious to be seen. Our model was much more stable than previous approaches. This collaboration was a wonderful example of why working with amateur and hobby paleontologists is so important."

Perez cautioned that because individual sharks vary in size, the team's methods still have a range of error of about 10 feet when applied to the largest individuals. It's also unclear exactly how wide megalodon's jaw was and difficult to guess based on teeth alone - some shark species have gaps between each tooth while the teeth in other species overlap.

"Even though this potentially advances our understanding, we haven't really settled the question of how big megalodon was. There's still more that could be done, but that would probably require finding a complete skeleton at this point," he said.

Perez continues to teach the megalodon tooth lesson, but its focus has changed.

"Since then, we've used the lesson to talk about the nature of science - the fact that we don't know everything. There are still unanswered questions," he said.

For Hendrickson, the lesson sparked her students' enthusiasm for science in ways that textbooks could not.

"Victor was an amazing role model for the kids. He is the personification of a young scientist that followed his childhood interest and made a career out of it. So many of these kids had never worked with or spoken to a scientist who respected their point of view and was willing to answer their questions."

Leder and Badaut co-authored the study.

In the quest for healthy aging and longer lifespan, Danish researchers at the University of Southern Denmark have collaborated with Swedish researchers at Karolinska Institutet to explore the anti-aging effects of football and team handball training in women.

In a current study published in Scientific Reports, the researchers investigated the effects of lifelong regular exercise on two of the central hallmarks of aging combined and showed that football and team handball have a positive effect on telomere length and mitochondrial function in women.

"Our legacy consists of DNA that is packed in chromosomes. When cells divide, the inheritance is copied, but with each cell division the ends of the DNA threads get shorter. The so-called telomeres are shortened, which causes us to age. It is remarkable that engaging in team sports such as football and handball helps women to maintain longer telomeres and healthy mitochondria. It may potentially increase their health span and, ultimately, lifespan, as shorter telomeres and mitochondrial dysfunction are both associated with a number of age-related diseases and mortality," says senior researcher Muhammad Asghar, the study's shared senior author, of the Department of Medicine, Solna at Karolinska Institutet.

Younger biological age in the cells as evaluated by telomere length

"We've recently shown that 65-80-year-old male football players are in excellent physical shape in comparison to untrained age-matched individuals, evidenced by markedly higher aerobic fitness, muscle mass and bone strength as well as a younger biological age in the cells as evaluated by telomere length," says Professor Peter Krustrup, the study's shared senior author, of the Department of Sports Science and Clinical Biomechanics at the University of Southern Denmark, and adds:

"Interestingly, the present study shows the same pattern, including a positive effect on mitochondrial health, in 60-80-year-old female team handball players, thereby supporting the evidence for an anti-aging potential of team sports."

"In addition to the positive findings in elderly team handball players, we observed that young female elite football players have ~23% longer telomeres in specific blood cells compared to untrained age-matched women," says PhD Marie Hagman, the study's first author, of the Department of Sports Science and Clinical Biomechanics at the University of Southern Denmark.

"These results are striking because differences in telomere length of that magnitude are not normally found in young participants. It should be noted, however, that this is a cross-sectional study and that our findings need to be confirmed by future randomised controlled trials," Hagman explains.

The study involved 129 healthy, non-smoking women, including young elite football players (YF, n=29, 18-30 yrs), young untrained controls (YC, n=30, 18-30 yrs), elderly team handball players (EH, n=35, 60-80 yrs) and elderly untrained controls (EC, n=35, 60-80 yrs). The study was the first to investigate the effects of lifelong regular exercise in humans on two of the central aging hallmarks combined.

Elite football and lifelong team handball training are associated with beneficial anti-aging cellular effects

The results of the study showed that elite football and lifelong team handball training are associated with beneficial anti-aging cellular effects in women. Specifically, young elite football players demonstrated higher telomere length and higher mtDNA copy number compared to young untrained controls, while elderly team handball players showed healthy mitochondria compared to elderly untrained controls. These cellular adaptations were also positively correlated with VO2max and the amount of weekly exercise, emphasizing the importance for these women, irrespective of age, to maintain a reasonable fitness and activity level.

Climate change and social inequality are two pressing issues that often overlap. A new study led by Princeton researchers offers a roadmap for cities to address inequalities in energy use by providing fine-grained methods for measuring both income and racial disparities in energy use intensity. Energy use intensity, the amount of energy used per unit floor area, is often used as a proxy for assessing the efficiency of buildings and the upgrades they receive over time. The work could guide the equitable distribution of rebates and other measures that decrease energy costs and increase efficiency.

Examining inequality in cities has been hampered by a lack of energy use data at fine spatial scales within cities. Until now, only Los Angeles has been able to use a data-driven approach to shine a light on where energy use inequalities exist, focusing specifically on the effect of income disparities. But according to new results reported in Proceedings of the National Academy of Sciences, to truly understand and fully address energy use inequality, cities must take an even more nuanced approach--one that unpacks race-related disparities from income. As the authors report, examining the issue solely through the lens of income risks missing significant race-related inequalities that exist beyond income effects.

"Often, in discussions about social justice, people sometimes ask, 'Oh, how do you know it's a race effect and not 'just' an income effect?'" said co-author Anu Ramaswami, a professor of civil and environmental engineering and the High Meadows Environmental Institute at Princeton University. "This paper actually shows you the data, that there's a structurally linked income-race effect, and an additional race effect even within the same income group."

Ramaswami and her colleagues arrived at their findings by studying two cities, Tallahassee, Florida, and St. Paul, Minnesota. The findings showed that when evaluating annual energy use, homes in the lowest income neighborhoods on average used 25-60% higher energy use per square foot compared to the highest income neighborhoods. What was more surprising was that within the income groups, predominantly non-white neighborhoods had higher energy use intensity compared to predominantly white neighborhoods.

"We were struck when we first saw these patterns," said Ramaswami, who also is Princeton's Sanjay Swani '87 Professor of India Studies and director of the Chadha Center for Global India.

The results were even starker considering seasonal energy use in summer and winter. Focusing on seasonal energy use intensity, the study uncovered disparities by income, and disparities by race within the lowest-income group, that can be greater than 150%, which are five times larger than the 25% disparity previously known in U.S. cities, based on the limited data availability in prior studies. The study found that households in low-income non-white neighborhoods report higher energy use intensity, reflective of lower energy efficiency of the buildings, as well as lower participation in rebate programs.

The method she and her colleagues developed can be applied in other cities and utility sectors (mobility, water, etc.) and is available now for adoption by cities interested in addressing racial inequalities. "We don't think it's only these two cities," Ramaswami said. "These effects are probably happening everywhere."

Inequalities surrounding income and race in the U.S. tend to be conflated because lower income communities often have higher non-white populations, while higher income areas tend to be predominantly white. To untangle these variables, Ramaswami and her co-authors worked with city officials and utility companies to obtain detailed energy use data.

"Part of the problem is that race and income are so intertwined, you need fine-scale data to actually unpack inequality," Ramaswami said. "Typically, cities get energy use data at the zip code level, which is very coarse, but we got data at the level of census blocks through a unique collaboration with our partner cities and utilities, who are committed to understanding baseline inequalities in their neighborhoods."

In total, the researchers obtained anonymized and aggregated data from utilities covering all 90,000 households in Tallahassee, and all 110,000 in St. Paul. They divided total household energy use in a neighborhood by the total square footage of the dwellings to compute the average energy use intensity for that neighborhood. They then compared energy use intensity across different neighborhood groups partitioned into five income brackets, and further by the racial composition of the neighborhoods within each income bracket.

The results revealed a number of surprises. In St. Paul, for example, the lowest income group had a 27% higher annual energy use intensity (use per square foot) compared to the highest income group. St Paul's result is comparable to the 25% disparity by income seen in Los Angeles. However, Tallahassee's disparity in annual electricity use intensity by income was found to be more than double at 66%. Furthermore, when the researchers further partitioned the income groups by racial composition of the census block groups, they found substantial additional disparities by race even within the same income groups. For example, in St. Paul, the poorest predominantly non-white neighborhoods had a 40% higher energy use intensity compared to poorest predominantly white neighborhoods. Such racial disparity was seen within all income brackets except for the very wealthiest block groups, which were majority white to begin with.

When the team took a closer look at seasonal energy use, -- i.e. energy used for heating and cooling in winter and summer--they found an up to 167% disparity in electricity use intensity between the lowest and highest -earning households in St. Paul, with the lowest-earning households footing that outsized energy burden. In Tallahassee, seasonal energy use showed large racial disparities within the lowest income group of the order of 156%.

"To my knowledge, this is the first study to show inequalities in urban energy use by race, and to show that it's different from energy use inequality by income," says Karen Seto, the Frederick C. Hixon Professor of Geography and Urbanization Science at Yale University, who was not involved in the research. "The study corroborates other studies that show significant within-city inequalities" by both race and income, she said, "whether it's exposure to heat or green space."

The researchers also examined household participation in several types of rebate programs designed to increase energy use efficiency and decrease costs. They found that homes in wealthier predominantly white neighborhoods were more likely to participate in rebate programs, while poorer predominantly non-white ones tended to slip through the cracks.

"Making this type of data visible is helpful for making people understand that infrastructure-related racial disparities are not just some abstract thing--it's real and you can see it in the data," Ramaswami said. "We all say we want social justice, but to get to that, it helps to be quantitative."

Ramaswami and her colleagues hope that cities across the country adopt their method to better understand their own energy equity dynamic. They are already working with officials in Austin, Texas, to apply this new approach.

Ultimately, they also hope to follow up on their findings to determine what is actually driving disparities in energy use intensity and rebate participation, so cities can use that information to further close the gap on inequalities.

"The new understanding gained from this study is already quite a lot," said Kangkang Tong, first author of the study and a postdoctoral researcher in civil and environmental engineering at Princeton University. "But it will take another several studies to really understand the reasons behind our findings, to help communities improve their energy use efficiency."

The study also addresses fundamental questions about the geographical scale researchers can use to measure social inequality in urban areas. The researchers found that choosing to study social inequality across city blocks as the unit of analysis provides different results than studying inequality across larger block groups or even larger census tracts. This is part of a fundamental question that scholars from many disciplines -- including geography, public health, computer science, mathematics, and political science -- are grappling with, called the modifiable areal unit problem. The problem is that measures of dispersion and inequality change as the spatial unit area of observation is modified - whether it is a city block, block group, census tract, or zip code. Ramaswami said the PNAS paper is the first to characterize the modifiable areal unit problem for the issue of energy use inequality in cities by exploring multiple metrics for energy use inequality across a range of scales. These findings are highly policy relevant because it means measuring disparity ratios from data aggregated at the block-level could give very different results from computing them from block-group or census tract-level data.

"This is also another area for further research, wherein policy-relevant questions can trigger fundamental scientific discoveries." Tong said.

High blood pressure, or hypertension, is the leading modifiable risk factor for cardiovascular diseases and premature death worldwide. And key to treating patients with conditions ranging from chest pain to stroke is understanding the intricacies of how the cells around arteries and other blood vessels work to control blood pressure. While the importance of metals like potassium and calcium in this process are known, a new discovery about a critical and underappreciated role of another metal - zinc - offers a potential new pathway for therapies to treat hypertension.

The study results were published recently in Nature Communications.

All the body's functions depend on arteries channeling oxygen-rich blood - energy - to where it's needed, and smooth muscle cells within these vessels direct how fast or slow the blood gets to each destination. As smooth muscles contract, they narrow the artery and increase the blood pressure, and as the muscle relaxes, the artery expands and blood pressure falls. If the blood pressure is too low the blood flow will not be enough to sustain a person's body with oxygen and nutrients. If the blood pressure is too high, the blood vessels risk being damaged or even ruptured.

"Fundamental discoveries going back more than 60 years have established that the levels of the calcium and potassium in the muscle surrounding blood vessels control how they expand and contract," say lead author Ashenafi Betrie, Ph.D., and senior authors Scott Ayton, Ph.D., and Christine Wright, Ph.D., of the Florey Institute of Neuroscience and Mental Health and The University of Melbourne in Australia.

Specifically, the researchers explain, potassium regulates calcium in the muscle, and calcium is known to be responsible for causing the narrowing of the arteries and veins that elevate blood pressure and restrict blood flow. Other cells that surround the blood vessel, including endothelial cells and sensory nerves, also regulate the calcium and potassium within the muscle of the artery, and are themselves regulated by the levels of these metals contained within them.

"Our discovery that zinc is also important was serendipitous because we'd been researching the brain, not blood pressure," says Betrie. "We were investigating the impact of zinc-based drugs on brain function in Alzheimer's disease when we noticed a pronounced and unexpected decrease in blood pressure in mouse models treated with the drugs."

In collaboration with researchers at the University of Vermont's Larner College of Medicine in the United States and TEDA International Cardiovascular Hospital in China, the investigators learned that coordinated action by zinc within sensory nerves, endothelial cells and the muscle of arteries triggers lower calcium levels in the muscle of the blood vessel. This makes the vessel relax, decreasing blood pressure and increasing blood flow. The scientists found that blood vessels in the brain and the heart were more sensitive to zinc than blood vessels in other areas of the body - an observation that warrants further research.

"Essentially, zinc has the opposite effect to calcium on blood flow and pressure," says Ayton. "Zinc is an important metal ion in biology and, given that calcium and potassium are famous for controlling blood flow and pressure, it's surprising that the role of zinc hasn't previously been appreciated."

Another surprising fact is that genes that control zinc levels within cells are known to be associated with cardiovascular diseases including hypertension, and hypertension is also a known side effect of zinc deficiency. This new research provides explanations for these previously known associations.

"While there are a range of existing drugs that are available to lower blood pressure, many people develop resistance to them," says Wright, who added that a number of cardiovascular diseases, including pulmonary hypertension, are poorly treated by currently available therapies. "New zinc-based blood pressure drugs would be a huge outcome for an accidental discovery, reminding us that in research, it isn't just about looking for something specific, but also about just looking."

A study conducted by a group of Brazilian researchers contributes to a deeper understanding of the molecular basis for schizophrenia, and potentially to the development of more specific and effective treatments for the disease. The medications currently available on the market act generically on the brain and can have severe adverse side effects.

Treatment of post-mortem samples from the hippocampus of schizophrenic patients with an NMDA receptor antagonist pointed to biological processes associated with the disease that are specific to neurons and oligodendrocytes. NMDA receptors are neurotransmitter receptors located in the postsynaptic membrane of neurons, and receive signals across the synapse from previous nerve cells.

The antagonist in question was MK-801, a drug that alters the neurotransmitter function of glutamate, mimicking in vitro what happens in schizophrenia (glutamate is the brain's primary excitatory neurotransmitter). Neurons treated with the substance displayed oxidative stress, one of the factors that can lead to brain degeneration, and apoptosis (programmed cell death). Oligodendrocytes, which synthesize the myelin sheath that insulates axons, were not altered in the same way. On the other hand, oligodendrocytes displayed differences associated with protein synthesis and myelin membrane organization.

The Laboratory of Neuroproteomics at the Institute of Biology of the University of Campinas (UNICAMP) used post-mortem brain tissue samples from patients with schizophrenia. The results, obtained in collaboration with the group led by Helder Nakaya, a professor at the University of São Paulo's School of Pharmaceutical Sciences (FCF-USP), are reported in an article published in European Archives of Psychiatry and Clinical Neuroscience.

"After culturing neurons and oligodendrocytes in the lab and treating them with MK-801, we analyzed the proteins in the brain and each cell type, cross-referencing the data. This enabled us to identify differences specific to neurons or oligodendrocytes, or common to both," said Daniel Martins-de-Souza, principal investigator for the study and head of the laboratory, which is supported by São Paulo Research Foundation - FAPESP.

Previous research found abnormal levels of glutamate in the brains of schizophrenic patients and linked glutamatergic neurotransmission dysfunction to NMDA receptor hypofunction. Glutamatergic neurotransmission is essential for cognition, learning and memory in humans.

"The treatment of neural cells with MK-801 revealed that neurons, oligodendrocytes and astrocytes are affected but present different responses to NMDA receptor hypofunction. NMDA receptor activation in oligodendrocytes is involved with their maturation, metabolic modulation and myelination around axons," the researchers write in the article.

An axon is part of a neuron that carries nerve impulses away from the cell body. Each neuron typically has one axon that connects it with other neurons via their synapses. Its filaments are insulated by a sheath made of myelin, a lipid-rich substance that prevents loss of energy during the transmission of electrical impulses between neurons.

"Thus, understanding the effects of glutamatergic dysregulation in both neurons and oligodendrocytes is crucial to a grasp of the role of these cellular counterparts in schizophrenia, especially in the hippocampal context," the article continues, adding that "we were able to find proteomic signatures in common between the hippocampus and MK-801-treated neurons, and between the hippocampus and the MK-801-treated oligodendrocytes". These findings will contribute to the development of treatments better targeted to the different dysfunctional biological processes in the various brain cell types.

According to PhD candidate Giuliana da Silva Zuccoli, first author of the article, lack of myelin or improper sheath formation may be part of the reason for cognitive and memory problems in schizophrenia.

Last year a study conducted at UNICAMP's Laboratory of Neuroproteomics with FAPESP's support had associated schizophrenia with dysfunctional oligodendrocytes that produce defective myelin.

FAPESP also supported the research that resulted in the article through funding for six other projects: 2018/14666-4, 2017/25588-1, 2019/00098-7, 2017/50137-3, 2012/19278-6 and 2013/08216-2.

23 million cases worldwide

Considered a severe debilitating mental disorder, schizophrenia affects some 23 million people worldwide, including 1.5 million Brazilians, according to the Pan American Health Organization (PAHO). It is characterized by thoughts or experiences that seem out of touch with reality, disorganized speech or behavior, and reduced participation in daily activities. Treatment involves a combination of medications, psychotherapy and specialized care. A clinical assessment is required to diagnose schizophrenia.

A promising methodology was developed last year to create a blood test that can diagnose schizophrenia by Brazilian researchers affiliated with the Federal University of São Paulo (UNIFESP) and UNICAMP. The test is the first to detect the disorder by analyzing biochemical and molecular alterations (more at: agencia.fapesp.br/34356).

In those with fatty liver disease, a person’s fat goes to their liver instead of their fat tissue, either because of an absence of fat depots, which is seen in the rare genetic disease lipodystrophy, or because the depots are too full, which is seen in people with obesity.

One third of these people will go on to develop nonalcoholic steatohepatitis, or NASH - an advanced form of fatty liver disease brought on by progressive inflammation and scarring in the organ.

In 2002, Michigan Medicine endocrinologist Elif Oral, M.D., who had just moved from the National Institutes of Health at the time, published her discovery that patients with severe lipodystrophy lack leptin, a hormone that helps curb appetite and control weight gain. When given leptin as a supplement, the patient’s serious metabolic abnormalities like NASH improved substantially.

Oral set out to U-M to further study the role of leptin, now in more common forms of NASH. Almost two decades later, her research team found that whether from a leptin deficiency or the presence of partial lipodystrophy, patients with NASH and relatively low leptin levels can mobilize the extra fat in their liver, out of their liver, and help reverse their condition by undergoing leptin therapy.

“Familial partial lipodystrophy often accompanies NASH. It’s a rare, genetic condition where patients have a lack of fat in their extremities but remain fat in their upper body,” Oral explained. “I wanted to test the effect of leptin in both those with this rare condition and those that just present with NASH to see if there would be a difference in therapeutic outcomes.”

This work, which is the first of its kind in humans and compiles research from three different studies, showed that leptin is an important signal in regulating fat deposition in the liver, and reversing fat deposition and its subsequent NASH.

During the lifetime of the study, the manufacturer of leptin changed several times, posing substantial bureaucratic obstacles for the research team to overcome.

“I could’ve moved on to something easier to study, but I wanted to see this through. This is my life’s work,” Oral said. “I’m grateful for all of my collaborators and co-authors for sticking with me through it all.”

Outlined in Med: Cell Press, Oral and her team conducted two open-label trials studying nine male patients with NASH and relatively low leptin levels (less than 9 ng/ml) and 23 patients with both partial lipodystrophy and NASH. Both groups received leptin therapy in the form of metreleptin for one year.

The trials consisted of male patients because Oral found that 35-40% of the men that had leptin levels measured had levels less than the twenty-fifth percentile of their body weight, making them ideal study candidates.

“Not all NASH is created equal. There’s a vast distribution of leptin levels in this patient population,” Oral said. “High levels of leptin, seen in obesity, can actually be causative of NASH so it was important to carefully select trial participants for low levels.”

After blind, paired liver biopsies, both groups were found to have reduced fat in the liver and lower NASH scores after 12 months of leptin therapy. The patients also had improved insulin sensitivity and body weight.

The findings are only applicable to leptin, but Oral thinks other molecules or treatments that activate leptin in the body could be of focus in future studies in an attempt to widen the therapeutic window for these patients.

After obesity is established, there’s little gain by giving someone leptin. However, a patient in the early overweight state may get value from undergoing leptin therapy, inspiring the research team to study leptin as a preventive weight control option in those at risk of crossing the obesity threshold and developing more fat in the liver.

“Although these results were encouraging, this justifies a larger trial,” Oral said. “But there’s no approved treatments for NASH of any form, so to have a therapeutic that can help at least a fraction of these patients is exciting.”

BOSTON - Automated emails and letters that provide personalized feedback related to cafeteria purchases at work may help employees make healthier food choices. That's the conclusion of a new study that was led by investigators at Massachusetts General Hospital (MGH) and is published in JAMA Network Open.

As many adults spend half (and sometimes more) of their waking hours working, the workplace provides a unique opportunity to promote health with programs that target obesity, unhealthy diets, and other risk factors for chronic diseases and premature death.

Building on findings from previous studies, researchers designed the ChooseWell 365 clinical trial to test a 12-month automated, personalized behavioral intervention to prevent weight gain and improve diet in hospital employees. For the trial, 602 MGH employees who regularly used the hospital's cafeterias were randomized to an intervention group or a control group. For one year, participants in the intervention group received two emails per week that included feedback on their previous cafeteria purchases and offered personalized health and lifestyle tips. They also received one letter per month with comparisons of their purchases with those of their peers, as well as financial incentives for healthier purchases. Control participants received one letter per month with general healthy lifestyle information.

"This novel workplace strategy was completely automated and did not require that people take time away from work to participate, making it ideal for busy hospital employees," explains lead author Anne N. Thorndike, MD, MPH, an investigator in the Division of General Internal Medicine at MGH and an associate professor of Medicine at Harvard Medical School.

Participants in the intervention group increased their healthy cafeteria food purchases to a greater extent than participants in the control group. They also purchased fewer calories per day. These differences were observed during the one-year intervention as well as during a year of additional assessments. There were no differences between the groups in terms of weight change at 12 or 24 months, however.

"Few if any prior workplace studies have been able to make sustained changes in dietary choices of employees," says Thorndike. "This study provides evidence that food purchasing data can be leveraged for delivering health promotion interventions at scale."

RUDN University chemists and their colleagues from Novosibirsk State University, Novosibirsk Institute of Organic Chemistry and The State Research Center of Virology and Biotechnology VECTOR have obtained a new class of compounds that inhibit the replication of the deadly Hantaan virus that affects blood vessels and internal organs of humans. The resulting substances were 5 times more effective than existing antiviral drugs. The results have been published Bioorganic & Medicinal Chemistry Letters.

The Hantaan virus causes acute haemorrhagic fever with renal syndrome (HFRS). The disease is common in the Asian part of Russia, China, Korea, Finland, Sweden, and the countries of eastern and central Europe. The main reservoir and carrier of the virus is the striped field mouse. A human can be infected through the skin or mucous membranes. The virus accumulates and replicates in the blood vessels causing their inflammation, affects the internal organs, primarily the kidneys. The mortality rate varies in different regions from 1% to 10-15%. There are no standard treatment regimens for HFRS -- the treatment is symptomatic. In this regard, the efforts of many scientific groups are focused on the cure development, including the synthesis of new antiviral drugs. RUDN chemists and their colleagues from Novosibirsk synthesized a new class of compounds based on the available natural substances (terpenes), which suppressed the reproduction of the virus in cells 5 times more effective than existing drugs in preliminary experiments.

"The study of antiviral drugs based on terpenes (hydrocarbons, which are found in large quantities in many plants and their essential oils), is very promising. We previously discovered a class of novel terpenoids active against the influenza virus, specifically camphor-based hydrazones. Now our goal is to find new drugs based on natural terpenes with specific activity to viruses causing HFRS", Fedor Zubkov, PhD, Associate Professor at RUDN department of Organic chemistry.

In previous studies chemists have synthesized derivatives of N-acylhydrazones of camphor and fenchone, which were active against smallpox and influenza viruses. One of these substances served as the starting point of this work. The new drug was obtained from natural camphor and fenchone. They can be extracted from the essential oils and resin of conifer trees. Using these substances, chemists obtained terpenic compounds and combined them with a heterocyclic fragment. As a result, a broad library of structurally diverse compounds was obtained - with or without a double bond, additional functional groups in the heterocyclic core, and so on. The composition of the resulting compounds was studied using 2D NMR spectroscopy.

Chemists tested the biological activity of the obtained compounds on pseudovirus system -- a biologically safe virus with the same glycoproteins on its surface as hantavirus. Such a model allows scientists to evaluate the bioactivity faster and safer than using a real virus. Chemists compared the results with the effects of broad-spectrum antiviral drugs Ribavirin and Triazavirin. 12 of the produced drugs demonstrated antiviral activity; one of them was 5 times more effective than Ribavirin and Triazavirin. Chemists concluded that the key structural feature necessary for the effective action of the drug the presence of the isoindole fragment attached to the terpene fragment.

"This class of compounds does not prevent the virus from entering the cell, but it inhibits its intracellular replication. Therefore, we can conclude that the therapeutic target of the obtained terpene complexes is the Hantaan virus protein responsible for replication", Alexandra Antonova, student at RUDN Department of Organic Chemistry.

Microgravity in space perturbs human physiology and is detrimental for astronaut health, a fact first realized during early Apollo missions when astronauts experienced inner ear disturbances, heart arrhythmia, low blood pressure, dehydration, and loss of calcium from their bones after their missions.

One of the most striking observations from Apollo missions was that just over half of astronauts became sick with colds or other infections within a week of returning to Earth. Some astronauts have even experienced re-activation of dormant viruses, such as the chickenpox virus. These findings stimulated studies on the effects of weak gravity, or "microgravity," on the immune system, which scientists have been exploring for decades of manned rockets launches, shuttle travel and space station stints, or sometimes by simulating space gravity in earthbound labs.

In the last study led by one of the first women astronauts, Millie Hughes-Fulford, PhD, researchers at UCSF and Stanford University now have shown that the weakening of an astronaut's immune system during space travel is likely due in part to abnormal activation of immune cells called T regulator cells (Tregs).

Tregs normally are triggered to ramp down immune responses when infection no longer threatens and are important regulators of immune responses in diseases ranging from cancer to COVID-19. In microgravity conditions, however, the researchers found changes in Tregs that prepared them to go to work even before the immune system was challenged. When they stimulated an immune response in human immune cells from blood samples in microgravity, with a chemical often used in research to mimic a disease pathogen, they found that Tregs helped suppress the immune response that was triggered. This unanticipated discovery is published online June 7 in the journal Nature Scientific Reports.

Hughes-Fulford became the first female payload specialist to orbit Earth with her experiments in 1991, and for decades, until her death due to leukemia in February, she studied the effects of microgravity on health, first with an emphasis on osteoporosis and later with a focus on the immune system. As a researcher at the San Francisco Veterans Affairs Medical Center and a UCSF faculty member long affiliated with the Department of Medicine, Hughes-Fulford mentored aspiring space scientists, including the co-principal investigators of this latest immunology study.

Jordan Spatz, PhD, a space scientist and UCSF medical student who became co-PI of the study after Hughes-Fulford's death, noted that as space travel becomes increasingly commercialized and more common, concerns over the health status of space travelers are likely to grow.

"Early in the space program, most astronauts were young and extremely healthy, but now they tend to have much more training and are older," Spatz said. "In addition, apart from astronauts, with the commercialization of space flight there will be many more older and less healthy individuals experiencing microgravity. From a space medical perspective, we see that microgravity does a lot of bad things to the human body, and we are hoping to gain the ability to mitigate some of the effects of microgravity during space travel."

The new study advanced earlier research led by Hughes-Fulford, confirming some of her previous findings from experiments in space and in simulated microgravity, while contributing additional molecular discoveries. Hughes-Fulford earlier had found weaker responses from T lymphocytes of the immune system, some of which attack specific pathogens directly and some of which help orchestrate the immune response.

"It's a double whammy," said co-PI Brice Gaudilliere, MD, PhD, an associate professor in the Department of Anesthesia at Stanford University School of Medicine. "There is a dampening of T lymphocyte immune activation responses, but also an exacerbation of immunosuppressive responses by Tregs." The researchers also found that "natural killer" lymphocytes were less active under simulated microgravity, while antibody-producing B cells appeared to be unaffected.

The researchers simulated microgravity in blood samples with a specialized, cylindrical, cell-culture vessel with motor-driven rotation, a long established microgravity research tool, but the method of single-cell analysis was unique. The scientists identified individual immune cells by specific type and used metal tags and mass spectroscopy to simultaneously detect and quantify dozens of proteins that play a role in immune function, in addition to confirming previously identified patterns of altered gene activation.

A new study from researchers at Johns Hopkins Bloomberg School of Public Health and colleagues suggests a slowdown in the use of convalescent plasma to treat hospitalized COVID-19 patients led to a higher COVID-19 mortality during a critical period during this past winter's surge.

U.S. hospitals began treating COVID-19 patients with convalescent plasma therapy--which uses antibody-rich blood from recovered COVID-19 patients--in the summer of 2020 when doctors were looking to identify treatments for the emerging disease. By the spring of 2021, doctors in the United States had treated over 500,000 COVID-19 patients with convalescent plasma. The use of convalescent plasma started declining late in 2020 after several large clinical trials showed no apparent benefit.

The researchers' analysis suggests that the decline in convalescent plasma use might have led to more than 29,000 excess COVID-19 deaths from November 2020 to February 2021.

The study was published online June 4 in the journal eLife.

"Clinical trials of convalescent plasma use in COVID-19 have had mixed results, but other studies, including this one, have been consistent with the idea that it does reduce mortality," says study senior author Arturo Casadevall, MD, PhD, Alfred and Jill Sommer Professor and Chair of the Department of the Molecular Microbiology and Immunology at the Bloomberg School.

The study was done in collaboration with researchers at Michigan State University and the Mayo Clinic. Casadevall and colleagues observed that while plasma use was declining late last year, the reported COVID-19 patient mortality rate was rising. That led them to hypothesize that the two phenomena were related.

In the study, the researchers compared the number of units of plasma distributed to U.S. hospitals from blood banks, on a per patient basis, to the number of reported COVID-19 deaths per hospital admission across the country.

One finding was that while the total use of plasma peaked last December and January during the winter surge in new COVID-19 patients, the use per hospitalized patient peaked in early October 2020--just as deaths per COVID-19 hospital admission bottomed. Thereafter, in the wake of reports of negative results from clinical trials, use of plasma per hospitalized patient fell sharply--and deaths per COVID-19 hospital admission rose.

The researchers analyzed the relationship between these two datasets and found a strong negative correlation, higher use rate being associated with lower mortality and vice versa. They also grouped periods of plasma use into five "quintile" groupings from lowest-use weeks to highest, and found a graded relationship between less use and higher mortality.

A model the researchers generated to fit the data suggested that the COVID-19 case fatality rate decreased by 1.8 percentage points for every 10-percentage point increase in the rate of plasma use. That model implied that there would have been 29,018 fewer deaths, from November 2020 to February 2021, if the peak use rate of early October had held. Moreover, it suggested that the use of plasma on the whole, as limited as it was, prevented about 95,000 deaths through early March of this year.

The researchers analyzed, and then rejected, the possibility that several other factors could explain away the link between less plasma use and more mortality. These factors included changes in the average age of hospitalized patients, and the emergence of new variants of the COVID-19-causing coronavirus.

As for why some clinical trials found no benefit for plasma use, the researchers note in their paper that many of the clinical trials with negative results had used plasma--mainly considered an antiviral treatment--relatively late in the course of COVID-19, when patients may have been too ill to benefit, and when the disease is driven mainly by immune-related responses rather than the coronavirus itself.

Casadevall notes that convalescent plasma remains under FDA Emergent Use Authorization in the U.S., and that it is readily available. "We hope that physicians, policymakers, and regulators will consider the totality of the available evidence, including our findings, when making decisions about convalescent plasma use in individual COVID-19 patients," Casadevall says.

LA JOLLA--(June 7, 2021) Type 1 diabetes, which arises when the pancreas doesn't create enough insulin to control levels of glucose in the blood, is a disease that currently has no cure and is difficult for most patients to manage. Scientists at the Salk Institute are developing a promising approach for treating it: using stem cells to create insulin-producing cells (called beta cells) that could replace nonfunctional pancreatic cells.

In a study published on June 7, 2021, in the journal Nature Communications, the investigators reported that they have developed a new way to create beta cells that is much more efficient than previous methods. Additionally, when these beta cells were tested in a mouse model of type 1 diabetes, the animals' blood sugar was brought under control within about two weeks.

"Stem cells are an extremely promising approach for developing many cell therapies, including better treatments for type 1 diabetes," says Salk Professor Juan Carlos Izpisua Belmonte, the paper's senior author. "This method for manufacturing large numbers of safe and functional beta cells is an important step forward."

In the current work, the investigators started with human pluripotent stem cells (hPSCs). These cells, which can be derived from adult tissues (most often the skin), have the potential to become any kind of cell found in the adult body. Using various growth factors and chemicals, the investigators coaxed hPSCs into beta cells in a stepwise fashion that mimicked pancreatic development.

Producing beta cells from hPSCs in the lab is not new, but in the past the yields of these precious cells have been low. With existing methods, only about 10 to 40 percent of cells become beta cells. By comparison, techniques used to create nerve cells from hPSCs have yields of about 80 percent. Another issue is that if undifferentiated cells are left in the mix, they could eventually turn into another kind cell that would be unwanted.

"In order for beta cell-based treatments to eventually become a viable option for patients, it's important to make these cells easier to manufacture," says co-first author Haisong Liu, a former member of the Belmonte lab. "We need to find a way to optimize the process."

To address the problem, the researchers took a stepwise approach to create beta cells. They identified several chemicals that are important for inducing hPSCs to become more specialized cells. They ultimately identified several cocktails of chemicals that resulted in beta cell yields of up to 80 percent.

They also looked at the ways in which these cells are grown in the lab. "Normally cells are grown on a flat plate, but we allowed them to grow in three dimensions," says co-first author Ronghui Li, a postdoctoral fellow in the Belmonte lab. Growing the cells in this way creates more shared surface area between the cells and allows them to influence each other, just as they would during human development.

After the cells were created, they were transplanted into a mouse model of type 1 diabetes, The model mice had a modified immune system that would not reject transplanted human cells. "We found that within two weeks these mice had a reduction of their high blood sugar level into normal range," says co-first author Hsin-Kai Liao, a staff researcher in the Belmonte lab. "The transplanted hPSC-derived beta cells were biologically functional."

The researchers will continue to study this technique in the lab to further optimize the production of beta cells. More research is needed to assess safety issues before clinical trials can be initiated in humans. The investigators say the methods reported in this paper may also be useful for developing specialized cells to treat other diseases.

WHAT:

New findings published in JAMA Neurology suggest there is no difference in cognitive outcomes at age 2 among children of healthy women and children of women with epilepsy who took antiseizure medication during pregnancy. The findings are part of the large research project Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD), which is a prospective, long-term study looking at outcomes in pregnant women with epilepsy and their children. The study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

This study reports findings from 382 children (292 children born to women with epilepsy and 90 born to healthy women) who were assessed for language development at age 2. The researchers also compared developmental scores with third trimester blood levels of antiseizure medication in these children.

Results suggest that children born to healthy women and those born to women with epilepsy do not show significant differences in language development scores at age 2. Neither was language development linked to third trimester blood levels of epilepsy medications. Most women with epilepsy in the study were taking lamotrigine and/or levetiracetam.

However, the study did find that those children born to mothers with the very highest levels of antiseizure medication in the blood during the third trimester did have somewhat lower scores on tests in the motor and general adaptive domains, which refer to skills related to self-care, such as feeding.

The children in this study will continue to be followed and will participate in additional cognitive tests through age 6. Results so far indicate that controlling epilepsy with these medications during pregnancy may be safe for babies.