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.
Findings from a study of patients who received radioactive iodine (RAI) treatment for hyperthyroidism show an association between the dose of treatment and long-term risk of death from solid cancers, including breast cancer. The study, led by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, was published July 1, 2019 in JAMA Internal Medicine.
“We identified a clear dose–response relationship between this widely used treatment and long-term risk of death from solid cancer, including breast cancer, in the largest cohort study to date of patients treated for hyperthyroidism,” said Cari Kitahara, Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics, lead author of the study . “We estimated that for every 1,000 patients treated currently using a standard range of doses, about 20 to 30 additional solid cancer deaths would occur as a result of the radiation exposure.”
RAI, which has been used widely in the United States for the treatment of hyperthyroidism since the 1940s, is one of three commonly used treatments for hyperthyroidism. The other two are anti-thyroid drugs, which have been rising in popularity, and surgical treatment, which is used least often.
Complement system appears to be double-edged sword depending on the eye disease
A new study shows that the complement system, part of the innate immune system, plays a protective role to slow retinal degeneration in a mouse model of retinitis pigmentosa, an inherited eye disease. This surprising discovery contradicts previous studies of other eye diseases suggesting that the complement system worsens retinal degeneration. The research was performed by scientists at the National Eye Institute (NEI), part of the National Institutes of Health, and appears in the Journal of Experimental Medicine.
Retinitis pigmentosa is an incurable and unpreventable blinding eye disease that affects 1 in 4,000 people.
“Much research is devoted to studying therapies that attempt to alter the immune system’s role in inherited diseases such as retinitis pigmentosa because such treatments would have broad applicability, regardless of a patient’s causative mutation,” said the study’s principal investigator Wai T Wong, M.D., Ph.D., chief the Neuron-Glia Interactions in Retinal Disease Section at NEI.
Retinal sections from a patient with retinitis pigmentosa show microglia (green) migrating into the photoreceptor layer (blue) once degeneration had begun. Inset shows microglia expressing C3 (red), which occurred in the context of photoreceptor degeneration.
National Institutes of Health scientists have used human skin cells to create what they believe is the first cerebral organoid system, or “mini-brain,” for studying sporadic Creutzfeldt-Jakob disease (CJD). CJD is a fatal neurodegenerative brain disease of humans believed to be caused by infectious prion protein. It affects about 1 in 1 million people. The researchers, from NIH’s National Institute of Allergy and Infectious Diseases (NIAID), hope the human organoid model will enable them to evaluate potential therapeutics for CJD and provide greater detail about human prion disease subtypes than the rodent and nonhuman primate models currently in use.
Human cerebral organoids are small balls of human brain cells ranging in size from a poppy seed to a small pea. Their organization, structure, and electrical signaling are similar to brain tissue. Because these cerebral organoids can survive in a controlled environment for months, nervous system diseases can be studied over time. Cerebral organoids have been used as models to study Zika virus infection, Alzheimer’s disease, and Down syndrome.
In a new study published in Acta Neuropathologica Communications, scientists at NIAID’s Rocky Mountain Laboratories discovered how to infect five-month-old cerebral organoids with prions using samples from two patients who died of two different CJD subtypes, MV1 and MV2. Infection took about one month to confirm, and the scientists monitored the organoids for changes in health indicators, such as metabolism, for more than six months. By the end of the study, the scientists observed that seeding activity, an indication of infectious prion propagation, was present in all organoids exposed to the CJD samples. However, seeding was greater in organoids infected with the MV2 sample than the MV1 sample. They also reported that the MV1-infected organoids showed more damage than the MV2-infected organoids.
Brightfield microscope image of an organoid during development, showing highly structured regions forming.
BASILICA procedure shows successful results for some high-risk patients
A novel technique has proven successful in preventing coronary artery obstruction during transcatheter aortic valve replacement (TAVR), a rare but often fatal complication. Called Bioprosthetic Aortic Scallop Intentional Laceration to prevent Iatrogenic Coronary Artery obstruction (BASILICA), the technique will increase treatment options for high-risk patients who need heart valve procedures. The findings by researchers at the National Institutes of Health will be published in the Journal of the American College of Cardiology: Cardiovascular Interventions on June 12.
TAVR, a procedure used to treat aortic valve stenosis, involves threading a long, thin, flexible tube, called a catheter, through the femoral artery in the leg to the heart. Aortic valve stenosis is a narrowing of the valve controlling blood leaving the heart to the rest of the body. This narrowing reduces blood flow to vital organs, resulting in shortness of breath, chest pain, blackouts, and heart failure.
For elderly or frail patients, TAVR offers an effective and less invasive alternative to open heart surgery. However, a small subset of these patients may develop coronary artery obstruction during the TAVR procedure. For more than half of these patients, this complication has been fatal.
Illustration of the BASILICA procedure. (A) a catheter directs an electrified guidewire through the base of the left aortic cusp into a snare in the left ventricular outflow tract; (B) after snare retrieval, the mid-shaft of the guidewire is electrified to lacerate the leaflet (C); (D) the leaflet splays after TAVR permitting coronary flow.
Results of study involving primates suggest that speech and music may have shaped the human brain’s hearing circuits
In the eternal search for understanding what makes us human, scientists found that our brains are more sensitive to pitch, the harmonic sounds we hear when listening to music, than our evolutionary relative the macaque monkey. The study, funded in part by the National Institutes of Health, highlights the promise of Sound Health, a joint project between the NIH and the John F. Kennedy Center for the Performing Arts that aims to understand the role of music in health.
“We found that a certain region of our brains has a stronger preference for sounds with pitch than macaque monkey brains,” said Bevil Conway, Ph.D., investigator in the NIH’s Intramural Research Program and a senior author of the study published in Nature Neuroscience. “The results raise the possibility that these sounds, which are embedded in speech and music, may have shaped the basic organization of the human brain.”
The study started with a friendly bet between Dr. Conway and Sam Norman-Haignere, Ph.D., a post-doctoral fellow at Columbia University’s Zuckerman Institute for Mind, Brain, and Behavior and the first author of the paper.
Tuned for Musical Pitch: NIH-funded scientists found that our brains may be uniquely sensitive to pitch, the harmonic sounds we hear when listening to speech or music.
Eliminating light while sleeping could reduce obesity
Sleeping with a television or light on in the room may be a risk factor for gaining weight or developing obesity, according to scientists at the National Institutes of Health. The research, which was published online June 10 in JAMA Internal Medicine, is the first to find an association between any exposure to artificial light at night while sleeping and weight gain in women. The results suggest that cutting off lights at bedtime could reduce women’s chances of becoming obese.
The research team used questionnaire data from 43,722 women in the Sister Study, a cohort study that examines risk factors for breast cancer and other diseases. The participants, aged 35-74 years, had no history of cancer or cardiovascular disease and were not shift workers, daytime sleepers, or pregnant when the study began. The study questionnaire asked whether the women slept with no light, a small nightlight, light outside of the room, or a light or television on in the room.
The scientists used weight, height, waist and hip circumference, and body mass index measurements taken at baseline, as well as self-reported information on weight at baseline and follow-up five years later. Using this information, the scientists were able to study obesity and weight gain in women exposed to artificial light at night with women who reported sleeping in dark rooms.
Youth who said they were teased or ridiculed about their weight increased their body mass by 33% more each year, compared to a similar group who had not been teased, according to researchers at the National Institutes of Health. The findings appear to contradict the belief that such teasing might motivate youth to change their behavior and attempt to lose weight. The study was conducted by Natasha A. Schvey, Ph.D., of the Uniformed Services University of the Health Sciences in Bethesda, Maryland, and colleagues at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. It appears in Pediatric Obesity.
The study involved 110 youth who were an average of 11.8 years of age when they enrolled. The participants were either overweight (defined as a body mass index above the 85th percentile) when they began the study or had two parents who were overweight or obese. At enrollment, they completed a six-item questionnaire on whether they had been teased about their weight. They then participated in annual followup visits for the next 15 years.
The researchers found that youth experiencing high levels of teasing gained an average of .20 kg (.44 lbs) per year more than those who did not. The authors theorize that weight-associated stigma may have made youths more likely to engage in unhealthy behaviors, such as binge eating and avoiding exercise. Another possible explanation is that the stress of being teased could stimulate the release of the hormone cortisol, which may lead to weight gain.
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.
