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:
Whether you’re shedding pounds with the help of effective new medicines, slimming down after weight loss surgery or cutting calories and adding exercise, there will come a day when the numbers on the scale stop going down, and you hit the dreaded weight loss plateau.
In a recent study, Kevin Hall, a researcher at the National Institutes of Health who specializes in measuring metabolism and weight change, looked at when weight loss typically stops depending on the method people were using todrop pounds. He broke down the plateau into mathematical models using data from high-quality clinical trials of different ways to lose weight to understand why people stop losing when they do. The study published Monday in the journal Obesity.
New study brings into question current policies on receiving secondary genomic findings
A study published today by researchers at the National Institutes of Health revealed that about half of individuals who said they don’t want to receive secondary genomic findings changed their minds after their healthcare provider gave them more detailed information. The paper, published in Genetics in Medicine, examines people's attitudes about receiving secondary genomic findings related to treatable or preventable diseases.
With the broader adoption of genome sequencing in clinical care, researchers and the bioethics community are considering options for how to navigate the discovery of secondary genomic findings. Secondary findings that come out of genome sequencing reflect information that is separate from the primary reason for an individual's medical care or participation in a study. For example, the genomic data of a patient who undergoes genome sequencing to address an autoimmune problem might reveal genomic variants that are associated with a heightened risk for breast cancer.
NIH study in monkeys finds that in visual decision-making, information relevant to the decision is broadcast widely
Researchers at the National Institutes of Health have discovered that decisions based on visual information, which involve a complex stream of data flowing forward and backwards along the brain’s visual pathways, is broadcast widely to neurons in the visual system, including to those that are not being used to make the decision. Feedback — such as information about a decision traveling back to neurons detecting visual features like color or shape — is thought to help the brain focus on visual information that is relevant to decision-making. The study, by scientists at the National Eye Institute (NEI), was published in Nature Communications.
“Why and how decision-making information is relayed back into the visual processing parts of the brain is an open question. Some theories posit that this type of feedback should be selective – only affecting those neurons that are involved in the decision,” said Hendrikje Nienborg, Ph.D., chief of the NEI Unit on Visual Decision Making and lead author of the study. “This study shows that decision-related feedback is spatially unselective, affecting neurons much more broadly than one might suppose.”
Feedback is used by the brain in many ways and many systems. When a decision is based on what we see, information about expectation or attention — such as where the object is, or about its features — is fed back to brain regions involved in the visual process, raising the activity of neurons involved in seeing the object or event in question.
Decision-signals about feature information, like object depth, are broadcast widely in the visual cortex via feedback during visual decision-making.
A new study authored by scientists at the National Institutes of Health, in collaboration with colleagues at the Centers for Disease Control and Prevention and Harvard University, Boston, and Emory University, Atlanta, suggests that one in four COVID-19 deaths in U.S. hospitals may have been attributed to hospitals strained by surging caseloads. Published in the Annals of Internal Medicine, the analysis looked at data from 150,000 COVID-19 inpatients from 558 U.S. hospitals from March to August of 2020. More than half of those admissions were patients arriving at hospitals during peak COVID-19 surges.
The surge–mortality relationship was stronger from June to August 2020 versus March to May 2020 (i.e., the contrast in outcomes between surging and non-surging hospitals appeared to grow over time), despite greater corticosteroid use and more judicious intubation during later and higher surging months. Surges were associated with mortality across ward, intensive care unit (ICU) and intubated patients.
These findings have implications for triage strategies, hospital preparedness, how healthcare facilities allocate resources and how public health authorities can assess and react to local data. To better highlight the strain experienced by hospitals, investigators used a measure of surge that considered not only the number of patients with COVID-19, but also illness severity and the hospitals’ typical bed capacity. By tracking these data, hospitals could preemptively divert patients and ask for help sooner — potentially avoiding excess deaths.
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.”
