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.
Large NIH-supported study showed that rural-dwelling Black men are at greatest risk
Adults living in rural areas of the United States have a 19% higher risk of developing heart failure compared to their urban counterparts, and Black men living in rural areas have an especially higher risk — 34%, according to a large observational study supported by the National Institutes of Health.
The study, one of the first to look at the link between living in rural America and first-time cases of heart failure, underscores the importance of developing more customized approaches to heart failure prevention among rural residents, particularly Black men. The study was largely funded by the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, and the findings, produced in collaboration with Vanderbilt University Medical Center, Nashville, Tennessee, publish today in JAMA Cardiology.
“We did not expect to find a difference of this magnitude in heart failure among rural communities compared to urban communities, especially among rural-dwelling Black men,” said Véronique L. Roger, M.D., M.P.H., the study’s corresponding author and a senior investigator with the Epidemiology and Community Health Branch in NHLBI’s Division of Intramural Research. “This study makes it clear that we need tools or interventions specifically designed to prevent heart failure in rural populations, particularly among Black men living in these areas.”
Study co-author Sarah Turecamo, a fourth-year medical student at New York University Grossman School of Medicine, New York City, and part of the NIH Medical Research Scholars Program, agreed. “It is much easier to prevent heart failure than to reduce its mortality once you have it,” Turecamo said.
The proportion of opioid overdose deaths involving buprenorphine, a medication used to treat opioid use disorder, did not increase in the months after prescribing flexibilities were put in place during the COVID-19 pandemic, according to a new study. These data provide evidence that may help to inform buprenorphine prescribing policies. Published today in JAMA Network Open,this study was a collaborative effort between researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and the Centers for Disease Control and Prevention (CDC).
These data are consistent with a recent study reporting that COVID-era expansion of methadone access for the treatment of opioid use disorder was not associated with an increase in methadone-involved overdose deaths.
In 2021, nearly 107,000 people died of a drug overdose, with 75 percent of those deaths involving an opioid. The overall rise in overdose deaths is largely attributable to the proliferation in the drug supply of illicit fentanyl, a highly potent synthetic opioid. Though the benefits of providing medication for opioid use disorder are well-known, only 22 percent of people with opioid use disorder receive medications. Buprenorphine, one of these medications, helps reduce opioid misuse, decrease risk for injection-related infectious diseases, and decrease risk for fatal and non-fatal overdoses.
“Research has shown beyond a doubt that medications for opioid use disorder are overwhelmingly beneficial and can be lifesaving, yet they continue to be vastly underused,” said NIDA Director and senior author, Nora Volkow, M.D. “Expanding more equitable access to these medications for people with substance use disorders is a critical part of our nation’s response to the overdose crisis. The findings from this study strengthen existing evidence suggesting that greater flexibility in prescribing may be one safe method for working toward this goal.”
NIH study provides new insights on role of gut in staph colonization
A promising approach to control Staphylococcus aureus bacterial colonization in people — using a probiotic instead of antibiotics — was safe and highly effective in a Phase 2 clinical trial. The new study, reported in The Lancet Microbe, found that the probiotic Bacillus subtilis markedly reduced S. aureus colonization in trial participants without harming the gut microbiota, which includes bacteria that can benefit people. The research was conducted by researchers at the National Institutes of Health led by Michael Otto, Ph.D., an NIH senior investigator at the National Institute of Allergy and Infectious Diseases (NIAID).
Methicillin-resistant S. aureus, or MRSA, is familiar to many people as a cause of serious disease. Less well known is that S. aureus often lives in the nose, on the body and in the gut without causing any harm. However, if the skin barrier is broken, or the immune system compromised, these colonizing bacteria can cause serious skin, bone, lung, and blood infections.
The prevention of S. aureus infections using approaches to 'decolonize' the body has gained increased attention as the spread of antibiotic resistance limits treatment options. Some decolonization strategies are controversial because they also require large amounts of antibiotics, raising concerns about damage to the microbiota and the development of antibiotic resistance. So far, it appears that only nasal S. aureus colonization can be targeted with topical antibiotics without doing too much harm, but bacteria quickly can recolonize in the nose from the gut.
MRSA (yellow) being ingested by neutrophil (purplish blue).
NIH study shows genotype-first approach uncovers new links to genetic conditions
National Institutes of Health researchers have published an assessment of 13 studies that took a genotype-first approach to patient care. This approach contrasts with the typical phenotype-first approach to clinical research, which starts with clinical findings. A genotype-first approach to patient care involves selecting patients with specific genomic variants and then studying their traits and symptoms; this finding uncovered new relationships between genes and clinical conditions, broadened the traits and symptoms associated with known disorders, and offered insights into newly described disorders. The study was published in the American Journal of Human Genetics.
“We demonstrated that genotype-first research can work, especially for identifying people with rare disorders who otherwise might not have been brought to clinical attention,” says Caralynn Wilczewski, Ph.D., a genetic counselor at the National Human Genome Research Institute’s (NHGRI) Reverse Phenotyping Core and first author of the paper.
Typically, to treat genetic conditions, researchers first identify patients who are experiencing symptoms, then they look for variants in the patients’ genomes that might explain those findings. However, this can lead to bias because the researchers are studying clinical findings based on their understanding of the disorder. The phenotype-first approach limits researchers from understanding the full spectrum of symptoms of the disorders and the associated genomic variants.
“Genomics has the potential to change reactive medicine into preventative medicine,” said Leslie Biesecker, M.D., NIH distinguished investigator, director of NHGRI’s Center for Precision Health Research and a senior author of the article. “Studying how taking a genotype-first approach to research can help us learn how to model predictive and precision medicine in the future.”
NIH findings may provide early clues about increased risks for advanced biological aging and premature death
Adults who stay well-hydrated appear to be healthier, develop fewer chronic conditions, such as heart and lung disease, and live longer than those who may not get sufficient fluids, according to a National Institutes of Health study published in eBioMedicine.
Using health data gathered from 11,255 adults over a 30-year period, researchers analyzed links between serum sodium levels — which go up when fluid intake goes down — and various indicators of health. They found that adults with serum sodium levels at the higher end of a normal range were more likely to develop chronic conditions and show signs of advanced biological aging than those with serum sodium levels in the medium ranges. Adults with higher levels were also more likely to die at a younger age.
“The results suggest that proper hydration may slow down aging and prolong a disease-free life,” said Natalia Dmitrieva, Ph.D., a study author and researcher in the Laboratory of Cardiovascular Regenerative Medicine at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.
A clinical trial led by the National Cancer Institute (NCI), part of the National Institutes of Health, has resulted in the first approval of a treatment for advanced alveolar soft part sarcoma (ASPS). The immunotherapy drug atezolizumab (Tecentriq) was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults and children 2 years and older with ASPS that has spread to other parts of the body or cannot be removed by surgery.
ASPS is an extremely rare cancer that affects mostly adolescents and young adults. The approval was based on data from a non-randomized phase 2 trial funded by NCI and led by Dr. Alice Chen, M.D., of the Developmental Therapeutics Clinic in NCI’s Division of Cancer Treatment and Diagnosis (DCTD). Genentech, a member of the Roche Group and the manufacturer of atezolizumab, provided the drug to NCI through a cooperative research and development agreement. The results of the study are being prepared for publication.
“Forty percent of the patients were treated at the NIH Clinical Center in Bethesda," said James H. Doroshow, M.D., director of DCTD. “Our ability to bring patients in from all over the world was a key factor in the ability to do the study.”
“This approval will make a huge impact in terms of a rare disease that has been particularly challenging to treat,” Dr. Chen noted.
Left frame: Normally, tumor cells (purple) evade the immune system’s T cells (pink) by expressing a checkpoint protein known as PD-L1. Right frame: Atezolizumab (Tecentriq) binds to PD-L1 and blocks it from binding to another checkpoint protein, PD-1. This helps T cells regain their ability to kill tumor cells.
Scientists used patient stem cells and 3D bioprinting to produce eye tissue that will advance understanding of the mechanisms of blinding diseases. The research team from the National Eye Institute (NEI), part of the National Institutes of Health, printed a combination of cells that form the outer blood-retina barrier — eye tissue that supports the retina's light-sensing photoreceptors. The technique provides a theoretically unlimited supply of patient-derived tissue to study degenerative retinal diseases such as age-related macular degeneration (AMD).
"We know that AMD starts in the outer blood-retina barrier," said Kapil Bharti, Ph.D., who heads the NEI Section on Ocular and Stem Cell Translational Research. "However, mechanisms of AMD initiation and progression to advanced dry and wet stages remain poorly understood due to the lack of physiologically relevant human models."
The outer blood-retina barrier consists of the retinal pigment epithelium (RPE), separated by Bruch’s membrane from the blood-vessel rich choriocapillaris. Bruch's membrane regulates the exchange of nutrients and waste between the choriocapillaris and the RPE. In AMD, lipoprotein deposits called drusen form outside Bruch's membrane, impeding its function. Over time, the RPE break down leading to photoreceptor degeneration and vision loss.
Steep, recent increase indicates COVID-19 associated with higher risk of endocarditis, NIH-supported study finds
The incidence rate of infective endocarditis — a rare but often fatal inflammation of the heart valves — among patients with cocaine use disorder or opioid use disorder increased from 2011 to 2022, with the steepest increase occurring from 2021 to 2022, a new study reports. Study findings contribute to expanding evidence of endocarditis as a significant and growing health concern for people who inject drugs, and further demonstrate that this risk has been exacerbated during the COVID-19 pandemic.
Among patients with either substance use disorder, those who were clinically diagnosed with COVID-19 faced a higher risk of a new endocarditis diagnosis as well as hospitalization following this diagnosis than those without COVID-19. Over the full 12-year period, the rate of endocarditis was three to eight times greater in patients with opioid and cocaine use disorder than those without.
The findings also showed that Black and Hispanic people faced a lower risk of COVID-19-associated endocarditis than non-Hispanic white people. The authors note this is consistent with higher prevalence of injection drug use in non-Hispanic white populations, compared to black or Hispanic populations. The study published today in Molecular Psychiatry, funded by agencies across the National Institutes of Health and led by the National Institute on Drug Abuse (NIDA).
“People with substance use disorder already face major impediments to proper healthcare due to lack of access and stigma,” said NIDA Director and co-corresponding study author, Nora D. Volkow, M.D. “Proven techniques like syringe service programs, which help people avoid infection from re-used or shared injection equipment, can help prevent this often fatal and costly condition.”
NIH findings may help researchers understand how genomic variation can affect behavioral differences in humans
National Institutes of Health researchers have shown that areas of the genome related to brain development harbor variants that may account for behavioral differences among different dog lineages. The study, funded by the National Human Genome Research Institute (NHGRI) and published in the journal Cell, involved citizen science projects that used DNA samples and surveys collected from dog owners around the world.
The researchers found that the genomic differences among dog breeds are related to the development of their nervous system. For dogs that herd sheep, the genomic differences involve how brain nerve cells, known as neurons, organize themselves to form neural circuits during the early stages of development.
Some of the genes associated with the different dog lineages may relate to genes that are involved in behavior of other species such as humans. These results suggest that dogs and humans may have similar biological pathways that give rise to the range of differences in brain function and behavior found within a species.
New study uses postmortem brain tissues to understand genomic differences in individuals with attention deficit hyperactivity disorder
Researchers at the National Institutes of Health have successfully identified differences in gene activity in the brains of people with attention deficit hyperactivity disorder (ADHD). The study, led by scientists at the National Human Genome Research Institute (NHGRI), part of NIH, found that individuals diagnosed with ADHD had differences in genes that code for known chemicals that brain cells use to communicate. The results of the findings, published in Molecular Psychiatry, show how genomic differences might contribute to symptoms.
To date, this is the first study to use postmortem human brain tissue to investigate ADHD. Other approaches to studying mental health conditions include non-invasively scanning the brain, which allows researchers to examine the structure and activation of brain areas. However, these studies lack information at the level of genes and how they might influence cell function and give rise to symptoms.
The researchers used a genomic technique called RNA sequencing to probe how specific genes are turned on or off, also known as gene expression They studied two connected brain regions associated with ADHD: the caudate and the frontal cortex. These regions are known to be critical in controlling a person’s attention. Previous research found differences in the structure and activity of these brain regions in individuals with ADHD.
