Research advances from the National Institutes of Health (NIH) Intramural Research Program (IRP) often make headlines. Read the news releases that describe our most recent findings:
BETHESDA, Md. (AP) — Sam Srisatta, a 20-year-old Florida college student, spent a month living inside a government hospital here last fall, playing video games and allowing scientists to document every morsel of food that went into his mouth.
From big bowls of salad to platters of meatballs and spaghetti sauce, Srisatta noshed his way through a nutrition study aimed at understanding the health effects of ultraprocessed foods, the controversial fare that now accounts for more than 70% of the U.S. food supply. He allowed The Associated Press to tag along for a day.
“Today my lunch was chicken nuggets, some chips, some ketchup,” said Srisatta, one of three dozen participants paid $5,000 each to devote 28 days of their lives to science. “It was pretty fulfilling.”
Examining exactly what made those nuggets so satisfying is the goal of the widely anticipated research led by National Institutes of Health nutrition researcher Kevin Hall.
“What we hope to do is figure out what those mechanisms are so that we can better understand that process,” Hall said.
NIH-funded study finds frequency, intensity of monthly migraines declined among those on higher fish oil diet
A diet higher in fatty fish helped frequent migraine sufferers reduce their monthly number of headaches and intensity of pain compared to participants on a diet higher in vegetable-based fats and oils, according to a new study. The findings by a team of researchers from the National Institute on Aging (NIA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), parts of the National Institutes of Health; and the University of North Carolina (UNC) at Chapel Hill, were published in the July 3 issue of The BMJ.
This study of 182 adults with frequent migraines expanded on the team’s previous work on the impact of linoleic acid and chronic pain. Linoleic acid is a polyunsaturated fatty acid commonly derived in the American diet from corn, soybean, and other similar oils, as well as some nuts and seeds. The team’s previous smaller studies explored if linoleic acid inflamed migraine-related pain processing tissues and pathways in the trigeminal nerve, the largest and most complex of the body’s 12 cranial nerves. They found that a diet lower in linoleic acid and higher in levels of omega-3 fatty acids (like those found in fish and shellfish) could soothe this pain pathway inflammation.
In a 16-week dietary intervention, participants were randomly assigned to one of three healthy diet plans. Participants all received meal kits that included fish, vegetables, hummus, salads, and breakfast items. One group received meals that had high levels of fatty fish or oils from fatty fish and lowered linoleic acid. A second group received meals that had high levels of fatty fish and higher linoleic acid. The third group received meals with high linoleic acid and lower levels of fatty fish to mimic average U.S. intakes.
Two U.S. Phase 1 clinical trials of a novel candidate malaria vaccine have found that the regimen conferred unprecedentedly high levels of durable protection when volunteers were later exposed to disease-causing malaria parasites. The vaccine combines live parasites with either of two widely used antimalarial drugs—an approach termed chemoprophylaxis vaccination. A Phase 2 clinical trial of the vaccine is now underway in Mali, a malaria-endemic country. If the approach proves successful there, chemoprophylaxis vaccination, or CVac, potentially could help reverse the stalled decline of global malaria. Currently, there is no vaccine in widespread use for the mosquito-transmitted disease.
The Sanaria vaccine, called PfSPZ, is composed of sporozoites, the form of the malaria parasite transmitted to people by mosquito bites. Sporozoites travel through blood to the liver to initiate infection. In the CVac trials, healthy adult volunteers received PfSPZ along with either pyrimethamine, a drug that kills liver-stage parasites, or chloroquine, which kills blood-stage parasites. Three months later, under carefully controlled conditions, the volunteers were exposed to either an African malaria parasite strain that was the same as that in the vaccine (homologous challenge) or a variant South American parasite (heterologous challenge) that was more genetically distant from the vaccine strain than hundreds of African parasites. Exposure in both cases was via inoculation into venous blood, which infects all unvaccinated individuals.
In children with rhabdomyosarcoma, or RMS, a rare cancer that affects the muscles and other soft tissues, the presence of mutations in several genes, including TP53, MYOD1, and CDKN2A, appears to be associated with a more aggressive form of the disease and a poorer chance of survival. This finding is from the largest-ever international study on RMS, led by scientists at the National Cancer Institute’s (NCI) Center for Cancer Research, part of the National Institutes of Health.
The study, published in the Journal of Clinical Oncology on June 24, provides an unprecedented look at data for a large cohort of patients with RMS, offering genetic clues that could lead to more widespread use of tumor genetic testing to predict how individual patients with this childhood cancer will respond to therapy, as well as to the development of targeted treatments for the disease.
“These discoveries change what we do with these patients and trigger a lot of really important research into developing new therapies that target these mutations,” said Javed Khan, M.D., of NCI’s Genetics Branch, who led the study.
NIH scientists discover that bacteria may drive activity of many hallmark aging genes in flies
To better understand the role of bacteria in health and disease, National Institutes of Health researchers fed fruit flies antibiotics and monitored the lifetime activity of hundreds of genes that scientists have traditionally thought control aging. To their surprise, the antibiotics not only extended the lives of the flies but also dramatically changed the activity of many of these genes. Their results suggested that only about 30% of the genes traditionally associated with aging set an animal’s internal clock while the rest reflect the body’s response to bacteria.
“For decades scientists have been developing a hit list of common aging genes. These genes are thought to control the aging process throughout the animal kingdom, from worms to mice to humans,” said Edward Giniger, Ph.D., senior investigator, at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study published in iScience. “We were shocked to find that only about 30% of these genes may be directly involved in the aging process. We hope that these results will help medical researchers better understand the forces that underlie several age-related disorders.”
The results happened by accident. Dr. Giniger’s team studies the genetics of aging in a type of fruit fly called Drosophila. Previously, the team showed how a hyperactive immune system may play a critical role in the neural damage that underlies several aging brain disorders. However, that study did not examine the role that bacteria may have in this process.
Pictured is a Drosophila fly gut, a key source of bacteria.
Implications for functions ranging from tissue repair to antimicrobial responses
National Institutes of Health scientists and their collaborators have identified an internal communication network in mammals that may regulate tissue repair and inflammation, providing new insights on how diseases such as obesity and inflammatory skin disorders develop. The new research is published in Cell.
The billions of organisms living on body surfaces such as the skin of mammals — collectively called microbiota — communicate with each other and the host immune system in a sophisticated network. According to the study, viruses integrated in the host genome, remnants of previous infections called endogenous retroviruses, can control how the host immune system and the microbiota interact, affecting tissue repair and antimicrobial defenses. Endogenous retroviruses can comprise up to 10% of all genes.
The newly discovered role of endogenous retroviruses adds to the scientific community’s understanding of certain diseases and inflammatory states and opens new research avenues. “Together, our results support the idea that mammals may have co-opted their endogenous viromes as a means to communicate with their microbiota, resulting in a multi-kingdom dialogue that controls both immunity and inflammation,” the authors state.
The microbiome is comprised of microorganisms that live in and on us and contribute to human health and disease.
NIH study suggests a link between cannabis use and higher levels of suicidal ideation, plan, and attempt
An analysis of survey data from more than 280,000 young adults ages 18-35 showed that cannabis (marijuana) use was associated with increased risks of thoughts of suicide (suicidal ideation), suicide plan, and suicide attempt. These associations remained regardless of whether someone was also experiencing depression, and the risks were greater for women than for men. The study published online today in JAMA Network Open and was conducted by researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.
“While we cannot establish that cannabis use caused the increased suicidality we observed in this study, these associations warrant further research, especially given the great burden of suicide on young adults,” said NIDA Director Nora Volkow, M.D., senior author of this study. “As we better understand the relationship between cannabis use, depression, and suicidality, clinicians will be able to provide better guidance and care to patients.”
The number of adults in the United States who use cannabis more than doubled from 22.6 million in 2008 to 45.0 million in 2019, and the number of daily or near-daily users almost tripled from 3.6 million to 9.8 million in 2019. Over the same time span, the number of adults with depression also increased, as did the number of people who reported suicidal ideation or plan or who died by suicide. To date, however, the relationship between trends in cannabis use and suicidality is not well understood.
Researchers estimate nearly 17 million undiagnosed cases in the U.S. by mid-July 2020
In a new study, National Institutes of Health researchers report that the prevalence of COVID-19 in the United States during spring and summer of 2020 far exceeded the known number of cases and that infection affected the country unevenly. For every diagnosed COVID-19 case in this time frame, the researchers estimate that there were 4.8 undiagnosed cases, representing an additional 16.8 million cases by July alone. The team’s analysis of blood samples from people who did not have a previously diagnosed SARS-CoV-2 infection, along with socioeconomic, health, and demographic data, offers insight into the undetected spread of the virus and subgroup vulnerability to undiagnosed infection.
“This study helps account for how quickly the virus spread to all corners of the country and the globe,” said Bruce Tromberg, Ph.D., director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB), one of the NIH institutes who run the NIH SARS-CoV-2 Seroprevalence Project. “The information will be invaluable as we assess the best public health measures needed to keep people safe, as new — and even more transmissible — variants emerge and vaccine antibody response changes over time.”
NIH researchers pursue innovative method for observing maternal and fetal health during pregnancy
Researchers at the National Institutes of Health have developed a prototype device that could potentially diagnose pregnancy complications by monitoring the oxygen level of the placenta. The device sends near-infrared light through the pregnant person’s abdomen to measure oxygen levels in the arterial and venous network in the placenta. The method was used to study anterior placenta, which is attached to the front wall of the uterus. The researchers described their results as promising but added that further study is needed before the device could be used routinely.
The researchers devised mathematical methods to study the passage of light through the skin, abdominal wall and uterine tissue to reach the placenta and calculate its oxygen levels. Currently, the device cannot monitor oxygen in women with a posterior placenta, which is attached to the back wall of the uterus, because the distance is too far for the light to travel. However, anterior placenta is associated with a higher rate of complications than posterior placenta, such as postpartum hemorrhage and an increased need for labor induction or cesarean delivery.
The prototype oxygen sensor next to a diagram of a fetus with forward-facing placenta.
NIH study breaks down pigment epithelium-derived factor to understand how it protects and stimulates retinal neurons
Researchers at the National Eye Institute (NEI) have determined how certain short protein fragments, called peptides, can protect neuronal cells found in the light-sensing retina layer at the back of the eye. The peptides might someday be used to treat degenerative retinal diseases, such as age-related macular degeneration (AMD). The study published today in the Journal of Neurochemistry. NEI is part of the National Institutes of Health.
A team led by Patricia Becerra, Ph.D., chief of the NEI Section on Protein Structure and Function, had previously derived these peptides from a protein called pigment epithelium-derived factor (PEDF), which is produced by retinal pigment epithelial cells that line the back of the eye.
“In the eye, PEDF protects neurons from dying. It prevents the invasion of blood vessels, it prevents inflammation, it has antioxidant properties— all these are beneficial properties,” said Becerra, the senior author of the study. Her studies suggest that PEDF is part of the eye’s natural mechanism for maintaining eye health. “PEDF may have a role for treating eye disease. If we want to exploit the protein for therapeutics, we need to separate out the regions responsible for its various properties and determine how each of them works.”
PEDF protein (center) has two domains with different functions. The 34-mer (blue, left) has anti-angiogenic properties. The 44-mer (green and yellow, right) protects and stimulates neurons. The 17-mer (yellow) is a smaller region of the 44-mer with the same function.
A new antibody testing study examining samples originally collected through the National Institutes of Health’s All of Us Research Program found evidence of SARS-CoV-2 infections in five states earlier than had initially been reported. These findings were published in the journal Clinical Infectious Diseases. The results expand on findings from a Centers for Disease Control and Prevention study that suggested SARS-CoV-2, the virus that causes COVID-19, was present in the U.S. as far back as December 2019.
In the All of Us study, researchers analyzed more than 24,000 stored blood samples contributed by program participants across all 50 states between Jan. 2 and March 18, 2020. Researchers detected antibodies against SARS-CoV-2 using two different serology tests in nine participants’ samples. These participants were from outside the major urban hotspots of Seattle and New York City, believed to be key points of entry of the virus in the U.S. The positive samples came as early as Jan. 7 from participants in Illinois, Massachusetts, Mississippi, Pennsylvania and Wisconsin. Most positive samples were collected prior to the first reported cases in those states, demonstrating the importance of expanding testing as quickly as possible in an epidemic setting.
“This study allows us to uncover more information about the beginning of the U.S. epidemic and highlights the real-world value of longitudinal research in understanding dynamics of emerging diseases like COVID-19,” said Josh Denny, M.D., M.S., chief executive officer of All of Us and an author of the study. “Our participants come from diverse communities across the U.S. and give generously of themselves to drive a wide range of biomedical discoveries, which are vital for informing public health strategies and preparedness.”
An All of Us team member handles participant samples in a lab.
