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.
Suicide risk among lesbian, gay, and bisexual adults varies considerably depending on the intersection between sexual identity and other aspects of identity, such as gender, age, and race/ethnicity, according to a study led by researchers at the National Institute of Mental Health (NIMH), part of the National Institutes of Health. The study, which examined data from a nationally representative survey of adults in the United States, also showed that lesbian, gay, and bisexual adults are overall more likely to report suicide-related thoughts, plans, and attempts within the past 12 months compared with heterosexual adults.
The findings, published in the American Journal of Preventive Medicine, indicate that the intersection of multiple social identities may compound suicide risk for some lesbian, gay, and bisexual individuals.
“This study demonstrates the importance of asking about sexual identity in national data collection efforts, and it highlights the pressing need for suicide prevention services that address the specific experiences and needs of lesbian, gay, and bisexual adults of different genders, ages, and race and ethnic groups,” said Rajeev Ramchand, Ph.D., Senior Advisor on Epidemiology and Suicide Prevention at NIMH and lead author of the study.
Scientists at the National Institutes of Health have found that a process in cells may limit infectivity of SARS-CoV-2, and that mutations in the alpha and delta variants overcome this effect, potentially boosting the virus’s ability to spread. The findings were published online in the Proceedings of the National Academy of Sciences. The study was led by Kelly Ten Hagen, Ph.D., a senior investigator at NIH’s National Institute of Dental and Craniofacial Research (NIDCR).
Since the coronavirus pandemic began in early 2020, several more-infectious variants of SARS-CoV-2, the virus that causes COVID-19, have emerged. The original, or wild-type, virus was followed by the alpha variant, which became widespread in the United States in early 2021, and the delta variant, which is the most prevalent strain circulating today. The variants have acquired mutations that help them spread and infect people more easily. Many of the mutations affect the spike protein, which the virus uses to get into cells. Scientists have been trying to understand how these changes alter the virus’s function.
“Throughout the pandemic, NIDCR researchers have applied their expertise in the oral health sciences to answer key questions about COVID-19,” said NIDCR Director Rena D’Souza, D.D.S., Ph.D. “This study offers fresh insights into the greater infectivity of the alpha and delta variants and provides a framework for the development of future therapies.”
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.
New evidence suggests that adding the targeted therapy ibrutinib (Imbruvica) to a standard chemotherapy regimen can improve how long some younger people with a specific form of diffuse large B-cell lymphoma (DLBCL) live. The findings, published Nov. 4, 2021, in Cancer Cell, come from a new analysis by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, of a previously conducted phase 3 clinical trial.
Initial results from that study, known as the PHOENIX trial, showed that combining ibrutinib with the standard chemotherapy regimen did not help patients with a form of DLBCL called non-GCB DLBCL to live longer overall. However, by analyzing tumor biopsy samples from patients on the trial, NCI researchers and their collaborators have now shown that younger patients with specific genetic subtypes of non-GCB DLBCL, called MCD and N1, had an exceptional response to the treatment combination, with all such patients alive without disease three years after diagnosis.
“People thought the trial didn’t work,” said Louis M. Staudt, M.D., Ph.D., chief of the Lymphoid Malignancies Branch in the Cancer for Cancer Research at NCI. “But there was something interesting going on — if you just considered younger patients under the age of 60, they had a real benefit from ibrutinib, and we now understand why.”
Younger patients with specific genetic subtypes of non-GCB DLBCL, called MCD and N1, had an exceptional response to the treatment combination.
Different mechanisms suppressed the virus in each person
Research led by scientists at the National Institutes of Health has identified two distinct ways that people with HIV can control the virus for an extended period after stopping antiretroviral therapy (ART) under medical supervision. This information could inform efforts to develop new tools to help people with HIV put the virus into remission without taking lifelong medication, which can have long-term side-effects.
The study involved two adults with HIV who began ART soon after acquiring the virus and continued with treatment for more than six years, successfully suppressing HIV. The individuals then joined an HIV clinical trial and stopped taking ART under medical supervision. The study team followed one of these people for four years and the other for more than five years, with study visits roughly every two to three weeks.
Scanning electron micrograph of an HIV-infected H9 T cell, colorized in Halloween colors.
A new, retrospective study of medical and insurance records indicates health care costs for people with a rare disease have been underestimated and are three to five times greater than the costs for people without a rare disease. The study, led by the National Institutes of Health’s National Center for Advancing Translational Sciences (NCATS), provides new evidence of the potential impact of rare diseases on public health, suggesting that nationwide medical costs for individuals with rare diseases are on par with those for cancer and heart failure. The study’s results were published Oct. 21 in the Orphanet Journal of Rare Diseases.
“There needs to be greater public awareness of the large and growing medical footprint of rare diseases in society,” said senior author Anne Pariser, M.D., director of the NCATS Office of Rare Diseases Research. “Only about 10% of rare diseases have an FDA-approved therapy for their treatment. The findings underscore an urgent need for more research, and earlier and more accurate diagnoses of and interventions for these disorders.”
Most of the approximately 7,000 to 10,000 known rare diseases disproportionately affect children, adolescents and young adults. Individually, most rare diseases might affect only a few hundred to a few thousand people worldwide. However, rare diseases are collectively common, affecting an estimated 25 million to 30 million people in the United States. Many of these diseases have a genetic cause, are serious or life-threatening and are hard to diagnose and treat.
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
