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.
The experimental antiviral drug remdesivir completely protected four African green monkeys from a lethal dose of Nipah virus, according to a new study in Science Translational Medicine from National Institutes of Health scientists and colleagues.
First identified in 1999 in Malaysia, Nipah virus is an emerging pathogen found primarily in Bangladesh and India. The virus is spread to humans by fruit bats; person-to-person transmission also occurs. Nipah virus can cause neurological and respiratory disease; the mortality rate is about 70%. Delayed relapse, manifesting as brain inflammation or encephalitis, can occur. An outbreak in May 2018 in India resulted in 23 cases and 21 deaths.
Gilead Sciences, Inc., is developing remdesivir and, in collaboration with scientists from the Centers for Disease Control and Prevention (CDC), performed initial laboratory studies evaluating the drug against Nipah virus. Researchers from CDC and NIH’s National Institute of Allergy and Infectious Diseases (NIAID) collaborated on the concept for the monkey study. NIAID then conducted the monkey studies with laboratory serology and pathology support from CDC. Animals infected with a lethal dose of Nipah virus received a first dose of intravenous remdesivir 24 hours after infection and then a daily intravenous dose for a total of 12 consecutive days. The NIAID team observed the animals for 92 days after infection, taking clinical samples 14 times during that span. The long period of observation allowed scientists adequate time to monitor the central nervous system for disease, which can be slow to develop when caused by Nipah virus. Two treated animals developed mild respiratory signs that resolved within three weeks; the other two treated animals showed no signs of illness. All four remained apparently healthy for the remainder of the study. Four untreated animals also received a lethal dose of Nipah virus. They began showing signs of illness within four days of infection and rapidly developed fatal disease within eight days.
Scanning electron micrograph of Nipah virus (yellow) budding from the surface of a cell.
New findings from a study by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, show that U.S. incidence rates for aggressive subtypes of uterine cancer rose rapidly among women ages 30 to 79 from 2000 to 2015. The findings also reveal racial disparities, including higher incidence of these aggressive subtypes and poorer survival — irrespective of subtype and cancer stage — among non-Hispanic black women than among women in other racial/ethnic groups.
The study, published May 22, 2019 in the Journal of Clinical Oncology, used population data from NCI’s Surveillance, Epidemiology, and End Results (SEER) database to evaluate trends in uterine cancer incidence rates for women overall and by race and ethnicity, geographic region, and histologic subtype (subtypes differentiated by how tumor tissue appears under a microscope). The authors corrected for hysterectomy prevalence, using data from the Behavioral Risk Factor Surveillance System, in estimating incidence rates of uterine cancer because women who have had a hysterectomy are no longer at risk for developing the disease. Many past studies of uterine cancer incidence did not include such a correction.
“Incidence rates of uterine cancer have been rising, and there have been previous reports of racial differences in incidence and survival rates, with disparities observed for non-Hispanic black women,” said Megan Clarke, Ph.D., lead author of the study and a postdoctoral fellow in NCI’s Division of Cancer Epidemiology and Genetics. “But few recent studies have corrected for hysterectomy, which can vary by race and ethnicity and by region. Correcting for hysterectomy prevalence gives us a more accurate picture of trends in overall incidence, as well as rates by race and ethnicity.”
Rates of aggressive uterine cancer subtypes rising in the U.S.
The transcatheter approach increases treatment options for high-risk patients
Researchers at the National, Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, have developed a novel technique that prevents the obstruction of blood flow, a common fatal complication of transcatheter mitral valve replacement (TMVR). The new method, called LAMPOON, may increase treatment options for high-risk patients previously ineligible for heart valve procedures. The Journal of the American College of Cardiology published the findings online on May 20.
TMVR is used to treat mitral valve stenosis, a narrowing of the valve that restricts blood flow into the main pumping chamber of the heart. It also treats regurgitation, which occurs when the valve leaks and causes blood to flow back through the valve. Untreated, these conditions can cause pulmonary hypertension, heart enlargement, atrial fibrillation, blood clots, and heart failure.
For elderly or frail patients, TMVR offers a less invasive alternative to open heart surgery. During TMVR, doctors replace the mitral valve by delivering an artificial valve through a long, thin, flexible tube, called a catheter, through blood vessels and into the heart. But in more than 50 percent of patients, the heart’s anatomy gets in the way. The heart leaflet is pushed back and blocks blood flow. This is known as left ventricular outflow tract (LVOT) obstruction, a common and the most life-threatening complication of TMVR.
“These patients have a failing mitral valve, are not able to undergo open heart surgery, and are now rejected as candidates for TMVR because of the very high risk of left ventricular outflow tract obstruction,” said study author Jaffar M. Khan, M.D., clinician at NHLBI.
Small-scale trial is the first randomized, controlled research of its kind
People eating ultra-processed foods ate more calories and gained more weight than when they ate a minimally processed diet, according to results from a National Institutes of Health study. The difference occurred even though meals provided to the volunteers in both the ultra-processed and minimally processed diets had the same number of calories and macronutrients. The results were published in Cell Metabolism.
This small-scale study of 20 adult volunteers, conducted by researchers at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), is the first randomized controlled trial examining the effects of ultra-processed foods as defined by the NOVA classification system. This system considers foods “ultra-processed” if they have ingredients predominantly found in industrial food manufacturing, such as hydrogenated oils, high-fructose corn syrup, flavoring agents, and emulsifiers.
Previous observational studies looking at large groups of people had shown associations between diets high in processed foods and health problems. But, because none of the past studies randomly assigned people to eat specific foods and then measured the results, scientists could not say for sure whether the processed foods were a problem on their own, or whether people eating them had health problems for other reasons, such as a lack of access to fresh foods.
“Though we examined a small group, results from this tightly controlled experiment showed a clear and consistent difference between the two diets,” said Kevin D. Hall, Ph.D., an NIDDK senior investigator and the study’s lead author. “This is the first study to demonstrate causality — that ultra-processed foods cause people to eat too many calories and gain weight.”
Researchers from the National Institutes of Health Kevin D. Hall, Ph.D., center, and Stephanie Chung, M.B.B.S., right, talk with a study participant at the NIH Clinical Center.
Testing the blood for free fatty acids could help doctors verify if children fasted before undergoing tests
Testing the blood for free fatty acids could help doctors verify if children fasted before undergoing tests for diabetes or other medical conditions, according to researchers at the National Institutes of Health. Their study appears in Pediatrics.
An overnight fast is required for the blood glucose test used to diagnose type 2 diabetes. However, earlier studies suggest that at least 6% of patients don’t fast sufficiently, potentially raising blood glucose and leading to an incorrect diagnosis and additional testing. Researchers from NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and other institutions paired the blood glucose test with a blood test for free fatty acids. Unlike blood glucose, which declines after a fast and increases after a meal, the blood level of free fatty acids increases after a fast and drops after a meal.
The researchers analyzed blood test results of children who participated in studies of obesity at the NIH Clinical Center. They compared free fatty acid test results of children who were admitted as inpatients — and whose food intakes were controlled by hospital staff — to those of children who participated as outpatients. They found that 9.7% of outpatients had lower free fatty acid levels, indicating they probably did not fast, compared to only 1.6% of inpatients. The authors suggest that testing for free fatty acids may help doctors interpret glucose test results in children, decreasing the number of children who need to be re-tested for high blood sugar.
NIH study suggests supplement that reduces risk of birth defects may also have maternal health benefit
Taking a folic acid supplement daily before pregnancy may reduce the risk of gestational, or pregnancy-related, diabetes, according to a study by researchers at the National Institutes of Health and other institutions. The findings appear in Diabetes Care.
Folic acid is the synthetic form of folate, or vitamin B9, which is found in leafy green vegetables, nuts, peas, beans and other foods. The U.S. Preventive Services Task Force recommends that all women of reproductive age take a daily supplement containing 400 to 800 micrograms of folic acid to reduce the risk of conceiving a child with a neural tube defect, a class of birth defects affecting the brain and spinal cord.
Gestational diabetes results when the level of blood sugar, or glucose, rises too high. It increases a woman’s chances for cesarean delivery and for blood pressure disorders during pregnancy. It also raises the risk of cardiovascular disease and type 2 diabetes later in life. For infants, gestational diabetes increases the risk of large birth size and of obesity during childhood and adulthood.
NIH-supported study highlights the importance of responsible portrayal of suicide by the media.
The Netflix show “13 Reasons Why” was associated with a 28.9% increase in suicide rates among U.S. youth ages 10-17 in the month (April 2017) following the shows release, after accounting for ongoing trends in suicide rates, according to a study published today in Journal of the American Academy of Child and Adolescent Psychiatry. The findings highlight the necessity of using best practices when portraying suicide in popular entertainment and in the media. The study was conducted by researchers at several universities, hospitals, and the National Institute of Mental Health (NIMH), part of the National Institutes of Health. NIMH also funded the study.
The number of deaths by suicide recorded in April 2017 was greater than the number seen in any single month during the five-year period examined by the researchers. When researchers analyzed the data by sex, they found the increase in the suicide rate was primarily driven by significant increases in suicide in young males. While suicide rates for females increased after the show’s release, the increase was not statistically significant.
“The results of this study should raise awareness that young people are particularly vulnerable to the media,” said study author Lisa Horowitz, Ph.D., M.P.H., a clinical scientist in the NIMH Intramural Research Program. “All disciplines, including the media, need to take good care to be constructive and thoughtful about topics that intersect with public health crises.”
Suicidal thoughts or actions (even in very young children) are a sign of extreme distress and should not be ignored.
If you or someone you know needs immediate help, contact the National Suicide Prevention Lifeline at 1-800-273-TALK (8255) or Crisis Text Line: text “home” to 741741.
Learn more about ways you can help someone who might be at risk for self-harm.
NIH scientists identify paradoxical response to HIV medication in five individuals
Antiretroviral therapy (ART) is usually very effective at suppressing HIV in the body, allowing a person’s immune system to recover by preventing the virus from destroying CD4+ T cells. Scientists have now identified a rare, paradoxical response to ART known as extreme immune decline, or EXID. Five individuals evaluated at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, experienced a significant decline in CD4+ T cell levels despite suppression of HIV below detectable levels for more than three years, according to a report published online today in JCI Insight. The research team was led by Irini Sereti, M.D., chief of the HIV Pathogenesis Section in NIAID’s Laboratory of Immunoregulation, and Andrea Lisco, M.D., Ph.D.
The NIAID researchers found that the immune systems of people with EXID fared even worse than those of another subset of individuals defined as immunological-non-responders, or INRs, who respond inadequately to ART. INR participants consistently taking ART for four years had CD4+ T cell counts that increased on average by 193 cells per microliter (µL) of blood. Participants who responded normally to ART increased their CD4+ T cell count by more than twice that amount. In contrast, the five participants with EXID experienced an average decline of 157 CD4+ T cells/µL while consistently maintaining viral suppression on ART.
Colorized scanning electron micrograph of a T lymphocyte.
NIH scientists and funding contributed to development of experimental treatment
A small clinical trial has shown that gene therapy can safely correct the immune systems of infants newly diagnosed with a rare, life-threatening inherited disorder in which infection-fighting immune cells do not develop or function normally. Eight infants with the disorder, called X-linked severe combined immunodeficiency (X-SCID), received an experimental gene therapy co-developed by National Institutes of Health scientists. They experienced substantial improvements in immune system function and were growing normally up to two years after treatment. The new approach appears safer and more effective than previously tested gene-therapy strategies for X-SCID.
These interim results from the clinical trial, supported in part by NIH, were published today in The New England Journal of Medicine.
Infants with X-SCID, caused by mutations in the IL2RG gene, are highly susceptible to severe infections. If untreated, the disease is fatal, usually within the first year or two of life. Infants with X-SCID typically are treated with transplants of blood-forming stem cells, ideally from a genetically matched sibling. However, less than 20% of infants with the disease have such a donor. Those without a matched sibling typically receive transplants from a parent or other donor, which are lifesaving, but often only partially restore immunity. These patients require lifelong treatment and may continue to experience complex medical problems, including chronic infections.
NIH research could be a step toward a treatment to prevent heart attacks
Two proteins that bind to stress hormones work together to maintain a healthy heart in mice, according to scientists at the National Institutes of Health and their collaborators. These proteins, stress hormone receptors known as the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), act in concert to help support heart health. When the signaling between the two receptors is out of balance, the mice have heart disease.
The work, published April 16 in Science Signaling, may lead to the development of therapeutic compounds that help people with an increased risk of a heart attack.
Stress increases risk of dying from heart failure by inducing adrenal glands to make a hormone called cortisol. Cortisol is involved in the fight-or-flight response and binds to GRs and MRs in different tissues of the body to reduce inflammation, among other functions. If the level of cortisol remains too high over a long period of time, common risk factors for heart disease may arise, such as increased cholesterol and glucose in the blood and high blood pressure.
Lead author Robert Oakley, Ph.D., first identified a malfunctioning GR in the 1990s when he was a graduate student working with John Cidlowski, Ph.D., at the University of North Carolina at Chapel Hill. Soon after the discovery, other scientists determined that people with above average amounts of this altered GR had greater risk of heart disease. Based on this finding, Oakley and Cidlowski tested a mouse strain without heart GR in their lab at the National Institute of Environmental Health Sciences (NIEHS), part of NIH. These animals spontaneously developed enlarged hearts leading to heart failure and death. When the team produced a mouse strain missing cardiac MR, the animals’ hearts functioned normally.
