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.
Different mRNA-1273 boosters are equally protective against variants
A booster dose of the mRNA-1273 COVID-19 vaccine given to rhesus macaques about six months after their primary vaccine series significantly increased levels of neutralizing antibodies against all known SARS-CoV-2 variants of concern, according to a new study from National Institutes of Health scientists and colleagues. The study, published in Science, also showed that the increased neutralizing antibody responses were sustained for at least eight weeks after the boost, were significantly higher than after the primary vaccine series, and generated high-level protection – meaning the ability to significantly limit virus from replicating in the lungs and nose. These data suggest that boosting triggers a strong immune memory response and potentially longer lasting immunity.
The researchers also determined that both the mRNA-1273 vaccine developed to target the original SARS-CoV-2 virus and a slightly modified version of the vaccine targeting the Beta variant, were equivalent in their ability to boost antibody responses and protect. Scientists at the Vaccine Research Center, part of NIH’s National Institute of Allergy and Infectious Diseases, led the project with collaborators from Emory University; Bioqual, Inc.; Moderna, Inc.; and Johns Hopkins University.
This study was performed six months ago when the SARS-CoV-2 Beta variant was a major concern. The researchers focused on the Beta variant because it has consistently shown the greatest ability to resist neutralization – by likely reducing vaccine effectiveness – according to the researchers. While Delta has become the dominant virus variant in the United States, because of its high transmissibility, it has only an intermediate ability to resist neutralization, the study authors state.
Colorized scanning electron micrograph of chronically infected and partially lysed cells (green) infected with a variant strain of SARS-CoV-2 virus particles (blue), isolated from a patient sample.
NIH study highlights the need to expand buprenorphine-based treatment while monitoring and reducing misuse
Data from a nationally representative survey indicate that in 2019, nearly three-fourths of U.S. adults reporting buprenorphine use did not misuse the medication in the past 12 months. In addition, buprenorphine misuse among people with opioid use disorder trended downward between 2015-2019, despite increases in the number of people receiving buprenorphine treatment. The study, published today in JAMA Network Open, was conducted by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and the Centers for Disease Control and Prevention.
Buprenorphine is an FDA-approved medication to treat opioid use disorder and to relieve severe pain. Buprenorphine used to treat opioid use disorder works by partially activating opioid receptors in the brain, which can help reduce opioid cravings, withdrawal, and overall use of other opioids.
In 2020, more than 93,000 people lost their lives due to drug overdoses, with 75% of those deaths involving an opioid. However, in 2019, less than 18% of people with a past-year opioid use disorder received medications to treat their addiction, in part due to stigma and barriers to accessing these medications. To prescribe buprenorphine for treatment of opioid use disorder, clinicians must do so within a certified Opioid Treatment Program, or submit a notice of intent to the federal government, and are limited in how many patients they can treat at one time. Only a small proportion of clinicians are eligible to treat opioid use disorder with buprenorphine, and even fewer prescribe the medication.
Findings suggest need for long-term studies of children born to mothers who experienced depression in pregnancy
Episodes of maternal stress or depression during pregnancy are associated with chemical modifications to placental genes, according to a study by researchers from the National Institutes of Health. The modifications involve DNA methylation — binding of compounds known as methyl groups to DNA — which can alter a gene’s activity. Some of the methylation changes associated with maternal depression occurred near genes involved in brain development, suggesting that maternal depression in pregnancy could have long-term implications for the mental development of the child.
The researchers undertook a genetic analysis, called an epigenome-wide association study, on samples of placentas delivered from 301 pregnant women who participated in a previous study. Study participants responded to questionnaires on their levels of stress and depression throughout their pregnancies. The researchers found that a history of stress was associated with methylation changes in two placental DNA sites and a history of depression was associated with changes in 16 placental DNA sites. Of the changes associated with depression, two were near genes linked to brain development.
Co-occurring health disorders appear to contribute to increased risk, NIH study suggests
An analysis of electronic health records of nearly 580,000 fully vaccinated people in the United States found that the risk of SARS-CoV-2 breakthrough infection among vaccinated patients with substance use disorders was low overall, but higher than the risk among vaccinated people without substance use disorders. The study was published today in World Psychiatry and led by researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and Case Western Reserve University in Cleveland, Ohio.
The study also found that co-occurring health conditions and adverse socioeconomic determinants of health, which are more common in people with substance use disorders, appear to be largely responsible for the increased risk of SARS-CoV-2 breakthrough infections. People with substance use disorders — such as alcohol, cannabis, cocaine, opioid, and tobacco use disorders — also had elevated rates of severe outcomes, including hospitalization and death, following breakthrough infections.
“First and foremost, vaccination is highly effective for people with substance use disorders, and the overall risk of COVID-19 among vaccinated people with substance use disorders is very low.” said NIDA Director Nora D. Volkow, M.D., and one of the lead authors on the study. "We must continue to encourage and facilitate COVID-19 vaccination among people with substance use disorders, while also acknowledging that even after vaccination, this group is at an increased risk and should continue to take protective measures against COVID-19.”
Francis S. Collins, M.D., Ph.D., today announced his decision to end his tenure as the director of the National Institutes of Health by the end of the year. Dr. Collins is the longest serving presidentially appointed NIH director, having served three U.S. presidents over more than 12 years.
“It has been an incredible privilege to lead this great agency for more than a decade,” said Dr. Collins. “I love this agency and its people so deeply that the decision to step down was a difficult one, done in close counsel with my wife, Diane Baker, and my family. I am proud of all we’ve accomplished. I fundamentally believe, however, that no single person should serve in the position too long, and that it’s time to bring in a new scientist to lead the NIH into the future. I’m most grateful and proud of the NIH staff and the scientific community, whose extraordinary commitment to lifesaving research delivers hope to the American people and the world every day.”
A physician-geneticist, Dr. Collins took office as the 16th NIH director on August 17, 2009, after being appointed by President Barack Obama and confirmed by the U.S. Senate. In 2017, he was asked to continue in his role by President Donald Trump, and in 2021, by President Joe Biden. Prior to becoming the NIH director, Dr. Collins served as the director of the National Human Genome Research Institute (NHGRI) from 1993-2008, where he led the international Human Genome Project, which culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book.
Francis S. Collins, M.D., Ph.D., Director, National Institutes of Health
The global COVID-19 pandemic has taken a toll on Black, American Indian/Alaska Native, and Latino individuals in the United States, causing more deaths by population size, both directly and indirectly, in these groups compared with white or Asian individuals. The findings, from a large surveillance study led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), appeared October 5, 2021, in Annals of Internal Medicine.
“Focusing on COVID-19 deaths alone without examining total excess deaths—that is, deaths due to non-COVID-19 causes as well as to COVID-19—may underestimate the true impact of the pandemic,” said Meredith S. Shiels, Ph.D., M.H.S., senior investigator in the Infections and Immunoepidemiology Branch in NCI’s Division of Cancer Epidemiology and Genetics, who led the study. “These data highlight the profound impact of long-standing inequities.”
Scientists at NCI have a long history of tracking mortality trends in the United States, mainly focusing on cancer death rates. More recently, these investigators have been applying their expertise in analyzing national surveillance data to better understand the impact of the COVID-19 pandemic on excess deaths by racial and ethnic group.
NIH study in mice demonstrates the importance of quickly addressing infection
Traumatic brain injury (TBI) and other injuries to blood vessels in the brain, like stroke, are a leading cause of long-term disability or death. Researchers at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health, have found a possible explanation for why some patients recover much more poorly from brain injury if they later become infected. The findings were published in Nature Immunology.
Making use of a mouse model for mild TBI (mTBI) that they had developed previously, the team of researchers led by NINDS scientist Dorian McGavern, Ph.D., discovered that viral, fungal, or a mimic for bacterial infections all impacted blood vessel repair within the meninges, the protective covering of the brain. When they looked closer, they observed that some cells of the immune system no longer moved into the site of the injury, which occurred in the uninfected animals, suggesting they were responding to systemic infection. The study also looked in a second injury model affecting the blood vessels in the brain, called a cerebrovascular injury (CVI), and saw a similar effect on repair.
“Evolution prioritizes mobilizing the immune system to fight off infection over repair,” said Dr. McGavern. “Because the body is dealing with a greater threat, cells that would normally repair the damaged blood vessels in or around the brain are needed elsewhere.”
Seven days after mTBI, the blood vessels (stained in red) in the tissues around the brain are not completely repaired. A marker for intact vessels was used (labeled in green) to distinguish fully functional blood vessels (yellow) from ones that are still damaged (red).
Patterns of methamphetamine use have become riskier, diversified across U.S. population
Overdose deaths involving methamphetamine nearly tripled from 2015 to 2019 among people ages 18-64 in the United States, according to a study by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health. The number of people who reported using methamphetamine during this time did not increase as steeply, but the analysis found that populations with methamphetamine use disorder have become more diverse. Published today in JAMA Psychiatry, the study suggests that increases in higher-risk patterns of methamphetamine use, such as increases in methamphetamine use disorder, frequent use, and use of other drugs at the same time, may be contributing to the rise in overdose deaths.
“We are in the midst of an overdose crisis in the United States, and this tragic trajectory goes far beyond an opioid epidemic. In addition to heroin, methamphetamine and cocaine are becoming more dangerous due to contamination with highly potent fentanyl, and increases in higher risk use patterns such as multiple substance use and regular use,” said NIDA Director Nora D. Volkow, M.D., one of the authors of the study. “Public health approaches must be tailored to address methamphetamine use across the diverse communities at risk, and particularly for American Indian and Alaska Native communities, who have the highest risk for methamphetamine misuse and are too often underserved.”
In 2020, more than 93,000 Americans died from drug overdoses, marking the largest one-year increase in overdose deaths ever recorded, according to provisional data from the U.S. Centers for Disease Control and Prevention. This increase has largely been driven by rising overdoses involving synthetic opioids, primarily fentanyl. Overdose deaths involving psychostimulants, and particularly methamphetamine, have also risen steeply in recent years, and many of these deaths involved use of an opioid at the same time. However, questions remain on how trends in methamphetamine use contribute to greater risk for overdose deaths.
Understanding Structure of HCV Proteins Could Aid in Vaccine Development
In a new paper published in Nature, scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, describe the structure of a key protein on the surface of the hepatitis C virus (HCV) and how it interacts with its receptor found on some human cells. The findings provide new leads for developing an HCV vaccine.
Hepatitis C is one of the most common bloodborne infections in the United States. Although it may not cause any symptoms in its early stages, untreated chronic infections can lead to severe liver damage, cancer, and death. Concerningly, infections are on the rise among young adults, largely due to exposure resulting from shared drug-injectables. No vaccine is available to prevent HCV infection.
HCV is usually transmitted via blood, such as during birth or when drug-injection equipment is shared. Because HCV may not cause any symptoms for years after initial infection, infections often go undetected. According to the U.S. Centers for Disease Control and Prevention, an estimated 2.4 million people are living with hepatitis C infection in the United States. More than half of all people infected with HCV are thought to develop chronic infection. HCV is a leading cause of cirrhosis, liver failure requiring transplant, and the leading cause of death from liver disease. Although effective antiviral drugs are available to treat HCV infection, they are expensive and do not prevent reinfection.
A transmission electron microscope image of hepatitis virus particles. Image credit: CDC/E.H. Cook, Jr.
Study lays the groundwork for potential new therapies for progressive multiple sclerosis
Chronic lesions with inflamed rims, or “smoldering” plaques, in the brains of people with multiple sclerosis (MS) have been linked to more aggressive and disabling forms of the disease. Using brain tissue from humans, researchers at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke (NINDS) built a detailed cellular map of chronic MS lesions, identifying genes that play a critical role in lesion repair and revealing potential new therapeutic targets for progressive MS. The study was published in Nature.
“We identified a set of cells that appear to be driving some of the chronic inflammation seen in progressive MS,” said Daniel Reich, M.D., Ph.D., senior investigator at NINDS. “These results give us a way to test new therapies that might speed up the brain’s healing process and prevent brain damage that occurs over time.”
Chronic active lesions are characterized by a slow, expanding rim of immune cells called microglia. Microglia normally help protect the brain, but in MS and other neurodegenerative diseases, they can become overactive and secrete toxic molecules that damage nerve cells. Other cells found at the edge of the lesions, such as astrocytes and lymphocytes, may also contribute to ongoing tissue damage. Prior studies suggest that microglia are the main culprits behind lesion expansion, but the exact types of cells found near lesions and their biological mechanisms are elusive.
Mapping multiple sclerosis lesions. Researchers used single-cell RNA sequencing to map the cells found at the edges of chronic MS lesions.
