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.
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.
Scientists from two independent research teams have discovered how the mislocalization of a protein, known as TDP-43, alters the genetic instructions for UNC13A, providing a possible therapeutic target that could also have implications in treating amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other forms of dementia. ALS and FTD are two neurodegenerative disorders in which many cases are linked by mislocalization of TDP-43, where instead of being primarily located in the nucleus of the cell where genes are activated, it forms aggregates outside the nucleus in multiple neurodegenerative diseases. Rare mutations in the TDP-43 gene are known to cause ALS, but almost all cases of ALS show mislocalization of TDP-43. The studies were published in Nature.
“ALS and FTD patients have long participated in genetic studies looking for changes in genes that might contribute to risk for disease,” said Thomas Cheever, Ph.D., program director at the National Institute of Neurological Disorders and Stroke (NINDS). “Here, we see two independent research teams converging to explain how one of these changes can be a critical factor contributing to an entire class of neurodegenerative diseases, as well as a potential therapeutic target.”
One study, which is a collaboration between the labs of Michael Ward, M.D., Ph.D., scientist at the National Institutes of Health’s NINDS, and Pietro Fratta, Ph.D., professor at the University College London Queen Square Motor Neuron Disease Centre in the United Kingdom, initially looked at lab-grown neurons derived from human induced pluripotent stem cells (iPSCs) — stem cells created from a patient’s tissue sample, often skin or blood. Using powerful genetic tools, the researchers created neurons that made much less TDP-43 protein than normal, and this resulted in the appearance of abnormal mRNA sequences inserted into the instructions used to make several other proteins. These abnormally inserted sequences, called cryptic exons, can result in a defective protein or can even prevent the protein from being made at all.
Study highlights the need for public health messaging strategies that address biases against all population groups that have been marginalized
People from all major racial and ethnic minority population groups in the United States report experiencing more COVID-19–related discrimination than white adults, a new study shows. COVID-19-related discrimination includes experiences of being threatened or harassed based on someone’s perception of another having COVID-19. To date, this is the largest study, with the most diverse participants, to examine discrimination related to COVID-19. The study was led by Paula D. Strassle, Ph.D., of the National Institute on Minority Health and Health Disparities (NIMHD), part of the National Institutes of Health, and was published in the American Journal of Public Health on Feb. 23, 2022.
In the study, researchers measured the prevalence of COVID-19–related discrimination in all major racial and ethnic groups in the United States, using data from the COVID-19’s Unequal Racial Burden (CURB) survey. They also analyzed the impact of other social and demographic factors on COVID-19–related discrimination. People from groups that have been marginalized, such as those who speak little to no English and those with lower levels of education, were also found to face more discrimination due to the pandemic.
Researchers collected information from 5,500 American Indian/Alaska Native, Asian, Black/African American, Hawaiian and Pacific Islander, Latino, white, and multiracial adults. The online survey was administered by YouGov from December 2020 to February 2021 and was available in English and Spanish. The survey asked whether participants had experienced COVID-19–related discriminatory behaviors, such as being called names or insulted, being threatened or harassed, or hearing racist comments, because the perpetrator thought the participant had COVID-19. The survey also asked whether participants felt that others acted afraid of them because they belonged to a racial/ethnic group misconceived to get COVID-19 more often.
After studying blood samples from 244 patients hospitalized for COVID-19, a group of researchers, including those who work at the National Institutes of Health, identified “rogue antibodies” that correlate with severe illness and may help explain mechanisms associated with severe blood clotting. The researchers found circulating antiphospholipid antibodies, which can be more common among people with autoimmune disorders, such as lupus. However, these “autoantibodies,” which target a person’s own organs and systems, can also be activated in response to viral infections and activate other immune responses.
Scientists compared the blood samples to those from healthy controls and found the COVID-19 samples contained higher levels of the antibody IgG, which works with other immune cells, such as IgM, to respond to immune threats. Higher levels of IgG were also associated with COVID-19 disease severity, such as in patients who required breathing assistance. The researchers observed similar patterns, but to a lesser extent, after analyzing blood samples from 100 patients hospitalized for sepsis, which can leave the body in inflammatory shock following a bacterial or viral infection.
IgG helps bridge a gap between innate and adaptive immune responses – a process that helps the body recognize, respond to, and remember danger. In normal cases, these features help protect the body from illness and infection. However, in some cases, this response can become hyperextended or altered and exacerbate illness. A unique finding from this study is that when researchers removed IgG from the COVID-19 blood samples, they saw molecular indicators of “blood vessel stickiness” fall. When they added these same IgG antibodies to the control samples, they saw a blood vessel inflammatory response that can lead to clotting.
National Institutes of Health researchers, led by Dr. Steven Rosenberg, MD, Ph.D., chief of the Surgery Branch at the Center for Cancer Research, National Cancer Institute (NCI), have found unique expression profiles in 50 genes that help identify rare anti-tumor lymphocytes that can infiltrate and help defeat metastatic solid epithelial tumors. To develop these profiles, a highly sensitive assay was designed that identified tumor-infiltrating lymphocytes (TIL) with cell surface receptors that can recognize the products of the very mutations that caused the cancer. The identification of these lymphocytes could help advance the development and effectiveness of personalized cancer immunotherapies for patients whose cancers do not respond to standard treatments.
This finding in TILs is especially important because it is agnostic to the type of tumor a patient has – it seems to have promise in stomach, esophageal, ovarian and breast cancers, among other types of tumors.
An experimental form of immunotherapy that uses an individual’s own tumor-fighting immune cells could potentially be used to treat people with metastatic breast cancer, according to results from an ongoing clinical trial led by researchers at the National Cancer Institute’s (NCI) Center for Cancer Research, part of the National Institutes of Health. Many people with metastatic breast cancer can mount an immune reaction against their tumors, the study found, a prerequisite for this type of immunotherapy, which relies on what are called tumor-infiltrating lymphocytes (TILs).
In a clinical trial of 42 women with metastatic breast cancer, 28 (or 67%) generated an immune reaction against their cancer. The approach was used to treat six women, half of whom experienced measurable tumor shrinkage. Results from the trial appeared Feb. 1, 2022, in the Journal of Clinical Oncology.
“It’s popular dogma that hormone receptor–positive breast cancers are not capable of provoking an immune response and are not susceptible to immunotherapy,” said study leader Steven A. Rosenberg, M.D., Ph.D., chief of the Surgery Branch in NCI’s Center for Cancer Research. “The findings suggest that this form of immunotherapy can be used to treat some people with metastatic breast cancer who have exhausted all other treatment options.”
Before TIL therapy, a woman with breast cancer had metastatic lesions in her chest wall (top, left) and liver (bottom, left). After receiving the immunotherapy, her tumors shrank completely, and recent scans (right) show that she remains cancer free more than five years later.
