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:
Saxophonist Joey Berkley was living his dream: he was playing jazz in New York City. But about 20 years ago, he noticed his left hand wasn’t cooperating. It got worse and worse.
“As soon as I picked my horn up and touched — literally just touched my horn — my hands would twist into pretzel shapes,” Berkley recalled in a conversation with Morning Edition host A Martinez.
Berkley was experiencing focal dystonia, a movement disorder marked by involuntary muscle contractions.
He said he “muscled through it” as best he could. But that meant he wasn’t just pressing down on the keys of his sax — he was crushing them. “My fingers would literally be bleeding afterwards,” he said. “I had to quit playing.”
Joey Berkley learned of an experimental procedure at the National Institutes of Health in Bethesda, Maryland, that involved placing an electrode directly into his brain.
NIH study suggests a small reduction in daily calories is beneficial for wellness
Reducing overall calorie intake may rejuvenate your muscles and activate biological pathways important for good health, according to researchers at the National Institutes of Health and their colleagues. Decreasing calories without depriving the body of essential vitamins and minerals, known as calorie restriction, has long been known to delay the progression of age-related diseases in animal models. This new study, published in Aging Cell, suggests the same biological mechanisms may also apply to humans.
Researchers analyzed data from participants in the Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE), a study supported by the National Institute on Aging (NIA) that examined whether moderate calorie restriction conveys the same health benefits seen in animal studies. They found that during a two-year span, the goal for participants was to reduce their daily caloric intake by 25%, but the highest the group was able to reach was a 12% reduction. Even so, this slight reduction in calories was enough to activate most of the biological pathways that are important in healthy aging.
"A 12% reduction in calorie intake is very modest," said corresponding author and NIA Scientific Director Luigi Ferrucci, M.D., Ph.D. "This kind of small reduction in calorie intake is doable and may make a big difference in your health."
Blood calcium levels normalized in clinical trial participants
An investigational drug, encaleret, restored calcium levels in people with autosomal dominant hypocalcemia type 1 (ADH1), a rare genetic disorder marked by an imbalance of calcium in the blood and urine, as well as abnormally low levels of parathyroid hormone, which regulates blood calcium levels. Led by clinician-scientists from the National Institute of Dental and Craniofacial Research (NIDCR) at the National Institutes of Health’s Clinical Center, results from the clinical trial are published in the New England Journal of Medicine.
In the mid-phase clinical trial, 13 participants with ADH1 received oral doses of the investigational drug for about 24 weeks. By the end of the trial, the treatment restored every participant’s blood calcium level to normal, and urine calcium approached normal levels. Levels of parathyroid hormone also normalized.
“It was amazing to see that every participant responded to the treatment. In literally minutes after taking the medication orally, the levels of parathyroid hormone increased dramatically,” said senior author and NIDCR endocrinologist Michael Collins, M.D.
Novel conditioning agent shows promise in animal models of sickle cell disease
Researchers at the National Institutes of Health have created a novel gene therapy procedure that could preserve fertility in people with sickle cell disease and other genetic blood conditions. Infertility is a high-risk and long-term side effect associated with current bone marrow transplantation and gene therapy approaches to treat sickle cell disease. It is a common reason people of reproductive age give for not pursuing these therapies.
The study, which appears in Nature Communications, describes the successful testing in animals of an antibody-drug conjugate, or conditioning agent, that exclusively targets blood-forming stem cells in the bone marrow. Conditioning agents are used in gene therapy to remove diseased stem cells and allow healthy stem cells to form. This new agent, called CD117-ADC, does not appear to damage other organs during the conditioning process. It is less toxic than the conventional agent now used for gene therapy in humans, called busulfan, which may cause ovarian failure in women and may stop sperm production in men, resulting in infertility.
NIH study reviews 25 years of data and finds AI/ML can detect common hormone disorder
Artificial intelligence (AI) and machine learning (ML) can effectively detect and diagnose Polycystic Ovary Syndrome (PCOS), which is the most common hormone disorder among women, typically between ages 15 and 45, according to a new study by the National Institutes of Health. Researchers systematically reviewed published scientific studies that used AI/ML to analyze data to diagnose and classify PCOS and found that AI/ML based programs were able to successfully detect PCOS.
“Given the large burden of under- and mis-diagnosed PCOS in the community and its potentially serious outcomes, we wanted to identify the utility of AI/ML in the identification of patients that may be at risk for PCOS,” said Janet Hall, M.D., senior investigator and endocrinologist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, and a study co-author. “The effectiveness of AI and machine learning in detecting PCOS was even more impressive than we had thought.”
PCOS occurs when the ovaries do not work properly, and in many cases, is accompanied by elevated levels of testosterone. The disorder can cause irregular periods, acne, extra facial hair, or hair loss from the head. Women with PCOS are often at an increased risk for developing type 2 diabetes, as well as sleep, psychological, cardiovascular, and other reproductive disorders such as uterine cancer and infertility.
“PCOS can be challenging to diagnose given its overlap with other conditions,” said Skand Shekhar, M.D., senior author of the study and assistant research physician and endocrinologist at the NIEHS. “These data reflect the untapped potential of incorporating AI/ML in electronic health records and other clinical settings to improve the diagnosis and care of women with PCOS.”
NIH researchers combined historical air quality data with breast cancer data from large U.S. study
Researchers at the National Institutes of Health found that living in an area with high levels of particulate air pollution was associated with an increased incidence of breast cancer. The study, published in the Journal of the National Cancer Institute, is one of the largest studies to date looking at the relationship between outdoor air pollution, specifically fine particulate matter, and breast cancer incidence. The research was done by scientists at the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI), both part of NIH.
The researchers saw that the largest increases in breast cancer incidence was among women who on average had higher particulate matter levels (PM2.5) near their home prior to enrolling in the study, compared to those who lived in areas with lower levels of PM2.5. Particulate matter is a mixture of solid particles and liquid droplets found in the air. It comes from numerous sources, such as motor vehicle exhaust, combustion processes (e.g., oil, coal), wood smoke/vegetation burning, and industrial emissions. The particulate matter pollution measured in this study was 2.5 microns in diameter or smaller (PM2.5), meaning the particles are small enough to be inhaled deep into the lungs. The Environmental Protection Agency has a website known as Air Now where residents can enter their zip code and get the air quality information, including PM2.5 levels, for their area.
“We observed an 8 percent increase in breast cancer incidence for living in areas with higher PM2.5 exposure. Although this is a relatively modest increase, these findings are significant given that air pollution is a ubiquitous exposure that impacts almost everyone,” said Alexandra White, Ph.D., lead author and head of the Environment and Cancer Epidemiology Group at NIEHS. “These findings add to a growing body of literature suggesting that air pollution is related to breast cancer.”
Researchers study confluence of multidrug resistance and hypervirulence among Klebsiella pneumoniae
New “hypervirulent” strains of the bacterium Klebsiella pneumoniae have emerged in healthy people in community settings, prompting a National Institutes of Health research group to investigate how the human immune system defends against infection. After exposing the strains to components of the human immune system in a laboratory “test tube” setting, scientists found that some strains were more likely to survive in blood and serum than others, and that neutrophils (white blood cells) are more likely to ingest and kill some strains than others. The study, published in mBio, was led by researchers at NIH’s National Institute of Allergy and Infectious Diseases (NIAID).
“This important study is among the first to investigate interaction of these emergent Klebsiella pneumoniae strains with components of human host defense,” Acting NIAID Director Hugh Auchincloss, M.D., said. “The work reflects the strength of NIAID’s Intramural Research Program. Having stable research teams with established collaborations allows investigators to draw on prior work and quickly inform peers about new, highly relevant public health topics.”
High levels of some minerals and metals in environmental water supplies may increase the risk of nontuberculous mycobacteria (NTM) pulmonary infections in people with cystic fibrosis, according to a new study from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. The study, appearing in Environmental Epidemiology, found the presence of the metals molybdenum and vanadium along with sulfate—a collection of mineral salts—in the U.S. municipal water system was associated with an increased incidence of NTM pulmonary infections, the leading cause of drinking-water associated illnesses.
Prior studies have shown that certain environmental conditions, including the presence of trace metals, likely contribute to a higher abundance of NTM in the water. Two of the most common forms of NTM bacteria in the U.S. are Mycobacterium avium complex (MAC) and M. abscessus. Both are linked to chronic lung infections in people with cystic fibrosis and other lung diseases. More than 35,000 people in the U.S. have cystic fibrosis, which causes the body to produce thick mucus, causing lung damage and trapping bacteria, increasing the likelihood of lung infection. This study measured whether the concentration of metals and minerals in the water had any influence on the probability of MAC and M. abscessus infection in people with cystic fibrosis.
NIH-supported, international study underscores importance of research of diverse populations
A gene variant found almost exclusively in the genomes of people of African ancestry increases the risk of developing Parkinson’s disease, according to an international study of nearly 198,000 participants with this genetic background. Published in The Lancet Neurology, the study results suggest the risk may be linked to a variant in the gene encoding β-glucocerebrosidase (GBA1), a protein known to control how cells in the body recycle proteins.
The study was led by scientists at the National Institutes of Health; the University College, London; and the University of Lagos, Nigeria. Although more research is needed to understand the role of environmental and other factors in these populations, the scientists found that those who carry one copy of the gene are about 1.5 times more likely to have Parkinson’s disease than those who have no copies whereas those who carry two copies are about 3.5 times more likely.
“To effectively treat Parkinson’s and truly any disease, we must study diverse populations to fully understand what the drivers and risk factors are for these disorders,” said Andrew B. Singleton, Ph.D., director, NIH Intramural Center for Alzheimer’s Related Dementias (CARD) and a study author. “These results support the idea that the genetic basis for a common disease can differ by ancestry, and understanding these differences may provide new insights into the biology of Parkinson’s disease.”
New sequence reveals genomic factors in fertility, including sperm production
An international research team has generated the first truly complete sequence of a human Y chromosome, the final human chromosome to be fully sequenced. The new sequence, which fills in gaps across more than 50% of the Y chromosome’s length, uncovers important genomic features with implications for fertility, such as factors in sperm production. The study, led by the Telomere-to-Telomere (T2T) Consortium, a team of researchers funded by the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, was published today in Nature.
The Y chromosome, along with the X chromosome, is often discussed for its role in sexual development. While these chromosomes play a central role, the factors involved in human sexual development are spread across the genome and very complex, giving rise to the array of human sex characteristics found among male, female and intersex individuals. These categories are not equivalent to gender, which is a social category. Additionally, recent work demonstrates that genes on the Y chromosome contribute to other aspects of human biology, such as cancer risk and severity.
When researchers completed the first human genome sequence 20 years ago, gaps were left in the sequences of all 24 chromosomes. However, unlike the small gaps sprinkled across the rest of the genome sequence — gaps that the T2T Consortium filled in last year — over half of the Y chromosome’s sequence remained a mystery.
A microscopy image created by National Institutes of Health researchers is part of the “Life Magnified” stamp panel issued today by the United States Postal Service (USPS). The NIH zebrafish image, which was taken to understand lymphatic vessel development in the brain, merges 350 individual images to reveal a juvenile zebrafish with a fluorescently tagged skull, scales and lymphatic system.
“Zebrafish are used as a model for typical and atypical human development. It is surprising how much we have in common with zebrafish,” said Diana W. Bianchi, director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), which generated the image. “NIH research affects our lives every day. My hope is that this postage stamp will help spur conversations and appreciation for the importance of basic science research.”
The image was taken by NICHD’s Daniel Castranova, an aquatic research specialist, with assistance from former trainee Bakary Samasa. The research was conducted in the Section on Vertebrate Organogenesis, led by principal investigator Brant Weinstein, Ph.D. The lab is devoted to understanding mechanisms guiding the formation of blood and lymphatic vessels. The image also received top honor in the 46th annual Nikon Small World Photomicrography Competition in 2020.