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.
Novel imaging biomarker could track interventions on coronary artery disease
Researchers have found that anti-inflammatory biologic therapies used to treat moderate to severe psoriasis can significantly reduce coronary inflammation in patients with the chronic skin condition. Scientists said the findings are particularly notable because of the use of a novel imaging biomarker, the perivascular fat attenuation index (FAI), that was able to measure the effect of the therapy in reducing the inflammation.
The study published online in JAMA Cardiology, has implications not just for people with psoriasis, but for those with other chronic inflammatory diseases, such as lupus and rheumatoid arthritis. These conditions are known to increase the risk for heart attacks and strokes. The study was funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health,
“Coronary inflammation offers important clues about the risk of developing heart artery disease,” said study’s senior author Nehal N. Mehta, M.D., a cardiologist and head of the Lab of Inflammation and Cardiometabolic Diseases at NHLBI. “Our findings add to the growing body of research that shows treating underlying inflammatory conditions may reduce the risk of cardiovascular diseases."
Coronary CT angiography image of the coronary arteries depicting the perivascular fat attenuation index before and after biologic therapy at one-year follow-up for patients with excellent response to biologic therapy.
Researchers show critical association between diabetes and previously unlinked ZRANB3 gene
National Institute of Health researchers have reported the largest genomic study of type 2 diabetes (T2D) in sub-Saharan Africans, with data from more than 5,000 individuals from Nigeria, Ghana and Kenya. Researchers confirmed known genomic variants and identified a novel gene ZRANB3, which may influence susceptibility to the disease in sub-Saharan African populations. The gene could also influence the development of T2D in other populations and inform further research.
In a study published in the journal Nature Communications, researchers analyzed genomic data available on participants through the Africa America Diabetes Mellitus study, the single largest diabetes genomic association study conducted on the continent. Using the information available from 5,231 people, they found many genomic variants to be significantly associated with T2D.
“Africa is the original cradle of all humanity, to which all humans can trace their genetic origin,” said Francis S. Collins, M.D., Ph.D., co-author of the paper and senior investigator with the NHGRI Medical Genomics and Metabolic Genetics Branch. “Thus, studying the genomes of Africans offers important opportunities to understand genetic variation across all human populations.”
Infants born to women exposed to high levels of air pollution in the week before delivery are more likely to be admitted to a newborn intensive care unit (NICU), suggests an analysis by researchers at the National Institutes of Health. Depending on the type of pollution, chances for NICU admission increased from about 4% to as much as 147%, compared to infants whose mothers did not encounter high levels of air pollution during the week before delivery. The study was led by Pauline Mendola, Ph.D., of the Epidemiology Branch at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. It appears in Annals of Epidemiology.
“Short-term exposure to most types of air pollutants may increase the risk for NICU admission,” Dr. Mendola said. “If our findings are confirmed, they suggest that pregnant women may want to consider limiting their time outdoors when air quality advisories indicate unhealthy conditions.”
Previous studies have linked elevated levels of certain kinds of air pollutants to higher risks for gestational diabetes and preeclampsia, a blood pressure disorder of pregnancy. Earlier research also has shown that infants born to women exposed to high levels of air pollutants are at risk for preterm birth, of being small for their gestational age at birth and of growing more slowly than normal in the uterus. Given these associations, the study authors sought to determine whether prenatal exposure to air pollution might increase the chance for NICU admission.
Small study suggests botulinum toxin may be potential treatment
Pelvic pain associated with endometriosis often becomes chronic and can persist (or recur) following surgical and hormonal interventions. According to results published in Regional Anesthesia & Pain Medicine, treating pelvic floor muscle spasm with botulinum toxin may relieve pain and improve quality of life. The study was conducted by scientists at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
“The botulinum toxin injections were incredibly effective in decreasing pain levels, as well as patients’ use of pain medications, including opioids,” said Pamela Stratton, M.D., a gynecologist and scientist at NINDS, who co-led the study with Barbara Karp, M.D., a neurologist and program director at NINDS. “Many of the women in our study reported that the pain had a profound effect on their quality of life, and this treatment may be able to help them get their lives back.”
Endometriosis occurs when the uterine tissue lining grows outside of the uterus and is estimated to affect up to 176 million women worldwide. It is an inflammatory condition that can lead to infertility and cause chronic pain. The usual gynecologic treatments include hormonal therapy and surgery to remove the growths. However, in many cases, pain returns after the interventions.
IRP study research uncovers specialized networks in the brain for processing face color
Anyone who has ever sensed that a person is sick simply by looking at their face has experienced the wealth of information conveyed by face color. A new study by the National Eye Institute (NEI), part of the National Institutes of Health, provides evidence that the human brain’s visual system is especially sensitive to the color of faces compared to the colors of other objects or things. Study results were published today in Nature Communications.
“The findings underscore the complexity of color perception. Far from operating as a reflex, color perception involves a set of sophisticated brain operations that ultimately assign value and meaning to what we see,” said the study’s lead investigator, Bevil Conway, Ph.D., head of the NEI Unit on Sensation, Cognition, and Action.
The findings also suggest that social communication cues from faces factored into evolutionary selective pressures that gave rise to trichromatic color vision in our ancestors 23 million years ago.
These face images illustrate how color plays a key role in how faces are read. Both images are manipulated away from normal, by about the same units in color (green in one direction, red in the other). Both color directions may be deemed meaningful in terms of indicating blushing or sickness.
Variants in the gene ARMC5 may be associated with high blood pressure among blacks, according to a National Institutes of Health study led by researchers at the Eunice Kennedy ShriverNational Institute of Child Health and Human Development (NICHD). The study team identified 17 variants in the ARMC5 gene that were associated with high blood pressure by analyzing genetic research databases that include those of African descent. The study is published in the July 3, 2019, issue of the Journal of the American Heart Association.
“High blood pressure increases a person’s risk for heart disease and stroke,” said Constantine A. Stratakis, M.D., D. Sc., NICHD Scientific Director and the study’s senior author. “The condition is more common among blacks, who also tend to get it at a younger age than whites do, and we are studying the underlying causes of this health disparity.”
Earlier work by the NICHD group linked some variants of ARMC5 to primary aldosteronism, a hormonal disorder that causes high blood pressure, among black patients. In the current study, the researchers analyzed datasets containing genetic information from large numbers of people, including NIH’s Minority Health Genomics and Translational Research Bio-Repository Database and the Genomics, Environmental Factors and Social Determinants of Cardiovascular Disease in African-Americans Study, which are based in the United States, as well as the UK Biobank.
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.
