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.
NIH researchers pursue innovative method for observing maternal and fetal health during pregnancy
Researchers at the National Institutes of Health have developed a prototype device that could potentially diagnose pregnancy complications by monitoring the oxygen level of the placenta. The device sends near-infrared light through the pregnant person’s abdomen to measure oxygen levels in the arterial and venous network in the placenta. The method was used to study anterior placenta, which is attached to the front wall of the uterus. The researchers described their results as promising but added that further study is needed before the device could be used routinely.
The researchers devised mathematical methods to study the passage of light through the skin, abdominal wall and uterine tissue to reach the placenta and calculate its oxygen levels. Currently, the device cannot monitor oxygen in women with a posterior placenta, which is attached to the back wall of the uterus, because the distance is too far for the light to travel. However, anterior placenta is associated with a higher rate of complications than posterior placenta, such as postpartum hemorrhage and an increased need for labor induction or cesarean delivery.
The prototype oxygen sensor next to a diagram of a fetus with forward-facing placenta.
NIH study breaks down pigment epithelium-derived factor to understand how it protects and stimulates retinal neurons
Researchers at the National Eye Institute (NEI) have determined how certain short protein fragments, called peptides, can protect neuronal cells found in the light-sensing retina layer at the back of the eye. The peptides might someday be used to treat degenerative retinal diseases, such as age-related macular degeneration (AMD). The study published today in the Journal of Neurochemistry. NEI is part of the National Institutes of Health.
A team led by Patricia Becerra, Ph.D., chief of the NEI Section on Protein Structure and Function, had previously derived these peptides from a protein called pigment epithelium-derived factor (PEDF), which is produced by retinal pigment epithelial cells that line the back of the eye.
“In the eye, PEDF protects neurons from dying. It prevents the invasion of blood vessels, it prevents inflammation, it has antioxidant properties— all these are beneficial properties,” said Becerra, the senior author of the study. Her studies suggest that PEDF is part of the eye’s natural mechanism for maintaining eye health. “PEDF may have a role for treating eye disease. If we want to exploit the protein for therapeutics, we need to separate out the regions responsible for its various properties and determine how each of them works.”
PEDF protein (center) has two domains with different functions. The 34-mer (blue, left) has anti-angiogenic properties. The 44-mer (green and yellow, right) protects and stimulates neurons. The 17-mer (yellow) is a smaller region of the 44-mer with the same function.
A new antibody testing study examining samples originally collected through the National Institutes of Health’s All of Us Research Program found evidence of SARS-CoV-2 infections in five states earlier than had initially been reported. These findings were published in the journal Clinical Infectious Diseases. The results expand on findings from a Centers for Disease Control and Prevention study that suggested SARS-CoV-2, the virus that causes COVID-19, was present in the U.S. as far back as December 2019.
In the All of Us study, researchers analyzed more than 24,000 stored blood samples contributed by program participants across all 50 states between Jan. 2 and March 18, 2020. Researchers detected antibodies against SARS-CoV-2 using two different serology tests in nine participants’ samples. These participants were from outside the major urban hotspots of Seattle and New York City, believed to be key points of entry of the virus in the U.S. The positive samples came as early as Jan. 7 from participants in Illinois, Massachusetts, Mississippi, Pennsylvania and Wisconsin. Most positive samples were collected prior to the first reported cases in those states, demonstrating the importance of expanding testing as quickly as possible in an epidemic setting.
“This study allows us to uncover more information about the beginning of the U.S. epidemic and highlights the real-world value of longitudinal research in understanding dynamics of emerging diseases like COVID-19,” said Josh Denny, M.D., M.S., chief executive officer of All of Us and an author of the study. “Our participants come from diverse communities across the U.S. and give generously of themselves to drive a wide range of biomedical discoveries, which are vital for informing public health strategies and preparedness.”
An All of Us team member handles participant samples in a lab.
In a commentary in Cell, scientists, administrators, staff, and leaders from the National Institutes of Health set forth a framework to end structural racism across the biomedical research enterprise and spur much needed widescale, systematic changes. Known as the UNITE initiative, it represents the first time all NIH Institutes and Centers are jointly focused on structural racism in biomedical science — both within the agency and throughout the biomedical workforce, as well as in the research NIH supports.
Recognizing that NIH-led diversity and inclusion programs have been valuable but not sufficient, the authors describe actions in process or planned to expand NIH efforts to the scale and scope essential to creating a more equitable ecosystem across biomedical science. These actions are informed and shaped by the five interacting committees of the NIH UNITE consortia, and include:
Increasing funding opportunities for projects that help to understand and address the impact of structural racism and discrimination on minority health and health disparities.
Understanding contributors to racial disparities in NIH funding and updating NIH Databook with grantee demographics by race and ethnicity.
Expanding current diversity and inclusion programs for senior investigators hired at NIH.
Enhancing recruitment of candidates from underrepresented groups and improving retainment of staff from diverse backgrounds and life experiences.
Gathering demographic data for both intramural and extramural staff across all job categories and ensuring transparency of that data.
Identifying and correcting any NIH policies and practices that perpetuate structural racism.
NIH scientists discover that the resting brain repeatedly replays compressed memories of what was just practiced
In a study of healthy volunteers, National Institutes of Health researchers have mapped out the brain activity that flows when we learn a new skill, such as playing a new song on the piano, and discovered why taking short breaks from practice is a key to learning. The researchers found that during rest the volunteers’ brains rapidly and repeatedly replayed faster versions of the activity seen while they practiced typing a code. The more a volunteer replayed the activity the better they performed during subsequent practice sessions, suggesting rest strengthened memories.
“Our results support the idea that wakeful rest plays just as important a role as practice in learning a new skill. It appears to be the period when our brains compress and consolidate memories of what we just practiced,” said Leonardo G. Cohen, M.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study published in Cell Reports. “Understanding this role of neural replay may not only help shape how we learn new skills but also how we help patients recover skills lost after neurological injury like stroke.”
The study was conducted at the NIH Clinical Center. Dr. Cohen’s team used a highly sensitive scanning technique, called magnetoencephalography, to record the brain waves of 33 healthy, right-handed volunteers as they learned to type a five-digit test code with their left hands. The subjects sat in a chair and under the scanner’s long, cone-shaped cap. An experiment began when a subject was shown the code “41234” on a screen and asked to type it out as many times as possible for 10 seconds and then take a 10 second break. Subjects were asked to repeat this cycle of alternating practice and rest sessions a total of 35 times.
In a study of healthy volunteers, NIH researchers discovered that our brains may replay compressed memories of learning new skills when we rest. Above is a map of the memory replay activity observed in the study.
Compound targets essential viral enzyme and prevents replication in cells
The experimental drug TEMPOL may be a promising oral antiviral treatment for COVID-19, suggests a study of cell cultures by researchers at the National Institutes of Health. TEMPOL can limit SARS-CoV-2 infection by impairing the activity of a viral enzyme called RNA replicase. The work was led by researchers at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The study appears in Science.
“We urgently need additional effective, accessible treatments for COVID-19,” said Diana W. Bianchi, M.D., NICHD Director. “An oral drug that prevents SARS-CoV-2 from replicating would be an important tool for reducing the severity of the disease.”
The study team was led by Tracey A. Rouault, M.D., head of the NICHD Section on Human Iron Metabolism. It discovered TEMPOL’s effectiveness by evaluating a more basic question on how the virus uses its RNA replicase, an enzyme that allows SARS-CoV-2 to replicate its genome and make copies of itself once inside a cell.
The small spherical structures in the center of the image are SARS-CoV-2 virus particles. The string-like protrusions extending from the cells are cell projections or pseudopodium.
A healthy diet around the time of conception through the second trimester may reduce the risk of several common pregnancy complications, suggests a study by researchers at the National Institutes of Health. Expectant women in the study who scored high on any of three measures of healthy eating had lower risks for gestational diabetes, pregnancy-related blood pressure disorders and preterm birth. The study was conducted by Cuilin Zhang, M.D., Ph.D., and colleagues at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in the American Journal of Clinical Nutrition.
The researchers analyzed dietary data collected multiple times during pregnancy from the NICHD Fetal Growth Study. Nearly 1,900 women responded to questionnaires on their diets at eight to 13 weeks of pregnancy and were asked to estimate what they ate in the previous three months. At 16 to 22 weeks and 24 to 29 weeks, the women identified what they ate in the previous 24 hours. Their responses were scored according to three measures of healthy eating: the Alternate Healthy Eating Index (AHEI), Alternate Mediterranean Diet (AMED), and Dietary Approaches to Stop Hypertension (DASH) diet. All three measures emphasize consumption of fruits, vegetables, whole grain, nuts and legumes while limiting red and processed meat.
Overall, the researchers found that following any of the diets around the time of conception through the second trimester was associated with a lower risk of gestational diabetes, hypertension, preeclampsia and preterm delivery. For example, women with a high AHEI score at 16 to 22 weeks had a 32% lower risk for gestational diabetes than women with a low AHEI score. Women with a high DASH score at eight to 12 weeks and 16 to 22 weeks had a 19% lower risk for pregnancy-related high blood pressure disorders. A high AMED score at 24 to 29 weeks or a high DASH score at 24 to 29 weeks was associated with a 50% lower risk for preterm birth.
NIH- and USU-led study links ALS to a fat manufacturing gene and maps out a genetic therapy
In a study of 11 medical-mystery patients, an international team of researchers led by scientists at the National Institutes of Health and the Uniformed Services University (USU) discovered a new and unique form of amyotrophic lateral sclerosis (ALS). Unlike most cases of ALS, the disease began attacking these patients during childhood, worsened more slowly than usual, and was linked to a gene, called SPTLC1, that is part of the body’s fat production system. Preliminary results suggested that genetically silencing SPTLC1 activity would be an effective strategy for combating this type of ALS.
“ALS is a paralyzing and often fatal disease that usually affects middle-aged people. We found that a genetic form of the disease can also threaten children. Our results show for the first time that ALS can be caused by changes in the way the body metabolizes lipids,” said Carsten Bönnemann, M.D., senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and a senior author of the study published in Nature Medicine. “We hope these results will help doctors recognize this new form of ALS and lead to the development of treatments that will improve the lives of these children and young adults. We also hope that our results may provide new clues to understanding and treating other forms of the disease.”
Dr. Bönnemann leads a team of researchers that uses advanced genetic techniques to solve some of the most mysterious childhood neurological disorders around the world. In this study, the team discovered that 11 of these cases had ALS that was linked to variations in the DNA sequence of SPLTC1, a gene responsible for manufacturing a diverse class of fats called sphingolipids.
A new study by researchers at the National Institutes of Health and their colleagues has found that SARS-CoV-2, the virus that causes COVID-19, does not appear to pose a threat to the safety of the nation’s blood supply. The analysis, published in Transfusion, supports current donor screening guidelines, including those used by the U.S. Food and Drug Administration, that do not require testing blood samples for the SARS-CoV-2 virus but do require that donors be screened for physical symptoms of COVID-19 and for infections that occurred within 14 days of the blood donation. The blood of donors with recent COVID-19 infections, or who develop infections after recent donations, cannot be used.
After reviewing test results for the presence of SARS-CoV-2 in thousands of blood donations across the country, researchers found no reason to alter the current blood donor screening practices that are in place because of the COVID-19 pandemic.
“This finding is good news for thousands of patients who may need a blood transfusion because of surgery or a disease that causes anemia, such as a rare blood-related condition or leukemia,” said Simone Glynn, M.D., M.P.H., chief of the Blood Epidemiology and Clinical Therapeutics Branch at the National Heart, Lung, and Blood Institute (NHLBI), which conducted the study along with National Institute of Allergy and Infectious Diseases (NIAID).
An environment in which family members support one another and express their feelings can reduce the effects of social deprivation on cognitive ability and development among adopted children, suggests a small study by researchers at the National Institutes of Health. In contrast, rule-driven households where family members are in conflict may increase an adopted child’s chances for cognitive, behavioral and emotional difficulties.
Researchers enrolled children who had spent at least eight months in Eastern European orphanages before their adoption by American families. The children ranged from 14 to 40 months of age and were evaluated with physical, psychological and developmental tests twice during the following two years. Families also responded to questionnaires on the children’s development and on various aspects of their home lives. The study included 10 adopted children and 19 similar children born to American families.
