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.
Despite decline, smoking cessation efforts still critical for people with substance use or other psychiatric disorders
Significant reductions in cigarette use were found among U.S. adults with major depression, substance use disorder, or both from 2006 to 2019, according to a new analysis of nationally representative survey data published today in JAMA. The study was conducted by researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, and the Substance Abuse and Mental Health Services Administration (SAMHSA). These findings suggest that groups at higher risk of cigarette smoking can be reached by, and may have benefitted from, tobacco use prevention and cessation efforts that have led to significant declines in tobacco use in the general population. At the same time, the findings highlight remaining disparities, documenting higher smoking rates in people with psychiatric disorders than in those without.
“This study shows us that, at a population-level, reductions in tobacco use are achievable for people with psychiatric conditions, and smoking cessation should be prioritized along with treatments for substance use, depression, and other mental health disorders for people who experience them,” said Nora Volkow, M.D., director of NIDA and co-author of the study. “Therapies to help people stop smoking are safe, effective, and may even enhance the long-term success of concurrent treatments for more severe mental health symptoms in individuals with psychiatric disorders by lowering stress, anxiety, depression, and by improving overall mood and quality of life.”
The study enrolled approximately 5,000 mothers and 6,000 children born between 2008 and 2010. Mothers responded periodically to questionnaires on their health and their children’s health and medical histories. Infertility treatments included in vitro fertilization (sperm and egg are combined in a laboratory dish and inserted in the uterus), drugs that stimulate ovulation, and a procedure in which sperm are inserted into the uterus.
Compared to children conceived without infertility treatment, children conceived after treatment were more likely to have persistent wheeze by age 3, a potential indication of asthma. At 7 to 9 years old, children conceived with treatment were 30% more likely to have asthma, 77% more likely to have eczema (an allergic condition resulting in rashes and itchy skin) and 45% more likely to have a prescription for an allergy medication.
New findings from the ongoing Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study suggest that certain rheumatoid arthritis drugs may lower incidence of Alzheimer’s disease and related dementias in people with cardiovascular disease. While the findings do not support broad use of these drugs for treating Alzheimer’s and related dementias, the results may point to a promising precision-medicine approach in specific groups of people at risk for developing these diseases. The research was published in JAMA Network Open and led by scientists at the National Institutes of Health’s National Institute on Aging in collaboration with researchers at Harvard Medical School, Boston; Rutgers University, New Brunswick, New Jersey; and Johns Hopkins University School of Medicine, Baltimore.
Discovering new drug targets in Alzheimer’s and related dementias is crucial for meeting the enormous public health challenge of these diseases. Prior studies on whether approved rheumatoid arthritis drugs lower the risk of developing dementia have produced mixed results. In this study, researchers analyzed data in Medicare claims from more than 22,000 people, looking at whether those with rheumatoid arthritis who took one of three different classes of arthritis drugs were protected from dementia. There were no statistically significant associations with lowered dementia risk except among those with cardiovascular disease who were treated with one class of arthritis drugs called TNF inhibitors. These inhibitors suppress the immune system by blocking the activity of TNF, which is a substance in the body that can cause inflammation and lead to immune-system diseases, including rheumatoid arthritis.
Norman E. “Ned” Sharpless, M.D., announced today that he has decided to step down from his position as director of the National Cancer Institute (NCI), part of the National Institutes of Health, a position he has held since 2017. Dr. Sharpless will continue as NCI director through April 29, 2022, to allow for a thorough transition. NCI Principal Deputy Director Douglas R. Lowy, M.D., will serve as NCI’s acting director effective April 30, 2022.
“Working at the National Cancer Institute has been the highlight of my career, and I am honored to have had the chance to serve my country in this role, alongside so many talented scientists and administrators,” Dr. Sharpless said. “I leave this job knowing that the talent and passion present at NCI, across the Biden-Harris Administration and throughout the cancer research community will continue to fuel tremendous progress for people with cancer in the years ahead.”
Dr. Sharpless was sworn in as the 15th director of NCI on Oct. 17, 2017. He also served as Acting Commissioner for Food and Drugs at the U.S. Food and Drug Administration (FDA) for seven months in 2019, before returning to the NCI directorship.
National Cancer Institute Director Norman E. “Ned” Sharpless, M.D.
Scientists have published the first complete, gapless sequence of a human genome, two decades after the Human Genome Project produced the first draft human genome sequence. According to researchers, having a complete, gap-free sequence of the roughly 3 billion bases (or “letters”) in our DNA is critical for understanding the full spectrum of human genomic variation and for understanding the genetic contributions to certain diseases. The work was done by the Telomere to Telomere (T2T) consortium, which included leadership from researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health; University of California, Santa Cruz; and University of Washington, Seattle. NHGRI was the primary funder of the study.
Analyses of the complete genome sequence will significantly add to our knowledge of chromosomes, including more accurate maps for five chromosome arms, which opens new lines of research. This helps answer basic biology questions about how chromosomes properly segregate and divide. The T2T consortium used the now-complete genome sequence as a reference to discover more than 2 million additional variants in the human genome. These studies provide more accurate information about the genomic variants within 622 medically relevant genes.
“Generating a truly complete human genome sequence represents an incredible scientific achievement, providing the first comprehensive view of our DNA blueprint,” said Eric Green, M.D., Ph.D., director of NHGRI. “This foundational information will strengthen the many ongoing efforts to understand all the functional nuances of the human genome, which in turn will empower genetic studies of human disease.”
According to consortium co-chair Adam Phillippy, Ph.D., whose research group at NHGRI led the finishing effort, sequencing a person’s entire genome should get less expensive and more straightforward in the coming years.
"In the future, when someone has their genome sequenced, we will be able to identify all of the variants in their DNA and use that information to better guide their healthcare,” Phillippy said. “Truly finishing the human genome sequence was like putting on a new pair of glasses. Now that we can clearly see everything, we are one step closer to understanding what it all means.”
Serum sodium levels may help identify adults with a greater chance of experiencing heart disease
Staying well-hydrated may be associated with a reduced risk for developing heart failure, according to researchers at the National Institutes of Health. Their findings, which appear in the European Heart Journal, suggest that consuming sufficient amounts of fluids throughout life not only supports essential body functioning, but may also reduce the risk of severe heart problems in the future.
Heart failure, a chronic condition that develops when the heart does not pump enough blood for the body’s needs, affects more than 6.2 million Americans, a little more than 2% of the population. It is also more common among adults ages 65 and older.
“Similar to reducing salt intake, drinking enough water and staying hydrated are ways to support our hearts and may help reduce long-term risks for heart disease,” said Natalia Dmitrieva, Ph.D., the lead study author and a researcher in the Laboratory of Cardiovascular Regenerative Medicine at the National Heart, Lung, and Blood Institute (NHLBI), part of NIH.
Findings resolve controversy about brain systems for attention
Minuscule involuntary eye movements, known as microsaccades, can occur even while one is carefully staring at a fixed point in space. When paying attention to something in the peripheral vision (called covert attention), these microsaccades sometimes align towards the object of interest. New research by National Eye Institute (NEI) investigators shows that while these microsaccades seem to boost or diminish the strength of the brain signals underlying attention, the eye movements are not drivers of those brain signals. The findings will help researchers interpret studies about covert attention and may open new areas for research into attention disorders and behavior. NEI is part of the National Institutes of Health.
Scientists working on the neuroscience of attention have recently become concerned that because both attention and eye movements, like microsaccades, involve the same groups of neurons in the brain, that microsaccades might be required for shifting attention.
“If microsaccades were driving attention, that would bring into question a lot of previous research in the field.” said Richard Krauzlis, Ph.D., chief of the NEI Section on Eye Movements and Visual Selection, and senior author of a study report on the research. “This work shows that while microsaccades and attention do share some mechanisms, covert attention is not driven by eye movements.”
While focusing their eyes on a soccer ball (yellow), a player might be paying attention to a teammate (pink) in their peripheral vision. Their overt attention would be on the ball, while covert attention would be on the teammate.
A large majority of individuals who reported and discussed non-suicidal self-injury on the social media platform Reddit described their experience in terms similar to those used to diagnose substance use disorder, according to researchers at the National Institutes of Health, who analyzed more than 350,000 posts and comments. People who posted on a forum dedicated to discussion of self-harm, called r/selfharm, from 2010 to 2019 often directly referred to their self-injuring activities as an “addiction,” citing cravings and escalating severity or tolerance, and regularly used terms employed by people recovering from substance use disorders, such as getting “clean” or “relapsing.” The study, published in Journal of Behavioral Addictions, was conducted by scientists at the National Institute on Drug Abuse (NIDA), part of NIH.
The findings also suggest that clinicians may better support people living with non-suicidal self-injury by adopting strategies used to diagnose and treat substance use disorders. Substance use disorders are diagnosed using evidence-based criteria described in the Diagnostic and Statistical Manual of Mental Disorders, now in its fifth edition (DSM-5).
“Non-suicidal self-injury is often private and hidden, and like substance use disorders, is highly stigmatized and can lead to significant harm if left undiagnosed and untreated,” said NIDA Director Nora Volkow, M.D. “Though this study alone does not demonstrate that self-injury can necessarily be classified as an addiction, learning more about the addictive-like behaviors of self-harm will be crucial to improve our understanding and treatment of this condition.”
An anti-inflammatory drug candidate, known as 3,6’-dithiopomalidomide (DP), designed by researchers at the National Institute on Aging (NIA), protected lab mice against cognitive decline by reducing brain inflammation. An international research team led by the NIA scientists published their findings in Alzheimer’s and Dementia: The Journal of the Alzheimer's Association. NIA is part of the National Institutes of Health.
The study results provide new evidence that brain inflammation — which occurs decades before Alzheimer’s symptoms are noticeable — is a key neuropathological pathway of interest in efforts to find potential treatments for Alzheimer’s.
To investigate whether brain inflammation was directly involved in cognitive loss, researchers used a mouse model specially designed to produce up to five times the normal levels of beta-amyloid plaques. These plaques are a hallmark sign of Alzheimer’s and are thought to contribute to a destructive inflammatory response in the brain. After four months of treatment with DP, the mice showed reduced brain inflammation and neuron death, and they had more neural connections in the brain areas responsible for memory and attention. DP-treated mice also showed improvement in behavioral laboratory tasks that test spatial and working memory as well as anxiety behaviors and motor function, results the researchers see as protective against cognitive impairment.
NIH study in ground squirrels suggests dual function for mitochondria in photoreceptor cells
Researchers at the National Eye Institute (NEI) have discovered that power-producing organelles in the eye’s photoreceptor cells, called mitochondria, function as microlenses that help channel light to these cells’ outer segments where it’s converted into nerve signals. The discovery in ground squirrels provides a more precise picture of the retina’s optical properties and could help detect eye disease earlier. The findings, published today in Science Advances, also shed light on the evolution of vision. NEI is part of the National Institutes of Health.
“We were surprised by this fascinating phenomenon that mitochondria appear to have a dual purpose: their well-established metabolic role producing energy, as well as this optical effect,” said the study’s lead investigator, Wei Li, Ph.D./B.M., who leads the NEI Retinal Neurophysiology Section.
The findings also address a long-standing mystery about the mammalian retina. Despite evolutionary pressure for light to be translated into signals and pass instantly from the retina to the brain, the trip is hardly direct. Once light reaches the retina, it must pass through multiple neural layers before reaching the outer segment of photoreceptors, where phototransduction (the conversion of light’s physical energy into cellular signals) occurs. Photoreceptors are long, tube-like structures divided into inner and outer segments. The last obstacle a photon must traverse before moving from the inner to the outer segment is an unusually dense bundle of mitochondria.
Those bundles of mitochondria would seem to work against the process of vision either by scattering light or absorbing it. So, Li’s team set out to investigate their purpose by studying cone photoreceptors from the 13-lined ground squirrel.
Using a modified confocal microscope, the researchers observed the optical properties of living cone mitochondria exposed to light. The path of light became concentrated with transmission from the inner to the outer segments of cone photoreceptors.
