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.
Older adults who participate weekly in many different types of leisure time activities, such as walking for exercise, jogging, swimming laps, or playing tennis, may have a lower risk of death from any cause, as well as death from cardiovascular disease and cancer, according to a new study led by researchers at the National Cancer Institute, part of the National Institutes of Health.
The findings suggest that it’s important for older adults to engage in leisure time activities that they enjoy and can sustain, because many types of these activities may lower the risk of death, the authors wrote.
The findings appear Aug. 24 in JAMA Network Open.
Using data from 272,550 adults between ages 59 and 82 who had completed questionnaires about their leisure time activities as part of the NIH-AARP Diet and Health Study, the researchers looked at whether participating in equivalent amounts of seven different exercise and recreational activities — including running, cycling, swimming, other aerobic exercise, racquet sports, golf, and walking for exercise — was associated with lowered risk of death.
NIH study suggests poverty combined with crowded housing or parental separation pose highest risks
Poverty, combined with other types of adversity in early childhood, is associated with greater chances of premature death in adulthood, compared to other adverse childhood experiences, according to a study of more than 46,000 people by researchers at the National Institutes of Health.
Compared to children who did not experience early life adversity, childhood poverty combined with crowded housing was associated with a 41% higher risk for premature death, and early poverty combined with separation from a parent was associated with a 50% increase in premature death. Those who experienced parental harshness and neglect had a 16% higher risk of premature death, and those who experienced family instability had a 28% higher risk for premature death.
The findings build upon earlier studies that linked individual types of adverse childhood experiences to risk of death, as well as other studies that demonstrated that death risk rose as exposure to childhood adversity increased. The current study identifies links between combinations of early childhood adversity and the overall chances of premature death.
“Understanding how patterns of early childhood adversity are associated with shortened life expectancy helps us better understand the toll of early experiences on human health and the extent that this toll carries over from childhood through adulthood,” said the study’s senior author, Stephen E. Gilman, Sc.D., chief of the Social and Behavioral Sciences Branch at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “In the long run, we hope that results such as ours can inform efforts to develop better interventions that would both reduce exposure to childhood adversity and reduce the health consequences of early adversity among exposed children.”
I am announcing today that I will be stepping down from the positions of Director of the National Institute of Allergy and Infectious Diseases (NIAID) and Chief of the NIAID Laboratory of Immunoregulation, as well as the position of Chief Medical Advisor to President Joe Biden. I will be leaving these positions in December of this year to pursue the next chapter of my career.
It has been the honor of a lifetime to have led the NIAID, an extraordinary institution, for so many years and through so many scientific and public health challenges. I am very proud of our many accomplishments. I have worked with — and learned from — countless talented and dedicated people in my own laboratory, at NIAID, at NIH and beyond. To them I express my abiding respect and gratitude.
Over the past 38 years as NIAID Director, I have had the enormous privilege of serving under and advising seven Presidents of the United States, beginning with President Ronald Reagan, on newly emerging and re-emerging infectious disease threats including HIV/AIDS, West Nile virus, the anthrax attacks, pandemic influenza, various bird influenza threats, Ebola and Zika, among others, and, of course, most recently the COVID-19 pandemic. I am particularly proud to have served as the Chief Medical Advisor to President Joe Biden since the very first day of his administration.
Dr. Anthony Fauci has served as Director of NIAID since 1984.
NIH study finds chemicals from Deepwater Horizon disaster associated with more wheeze
Researchers from the Gulf Long-term Follow-up Study (GuLF STUDY) found that workers involved in cleaning up the nation’s largest oil spill were 60% more likely than those who did not work on the cleanup to be diagnosed with asthma or experience asthma symptoms one to three years after the spill.
This ongoing study, led by the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, is the largest study to look at the health of workers who responded to the 2010 Deepwater Horizon oil spill in the Gulf of Mexico.
“This is the first study to ever look at specific chemicals from oil spills and link them to respiratory diseases,” said Dale Sandler, Ph.D., chief of the NIEHS Epidemiology Branch and lead researcher for the GuLF STUDY. “If you were an oil spill cleanup worker in the gulf experiencing wheezing or other asthma-like symptoms, it would be good to let your healthcare provider know you worked on the oil spill.”
The GuLF STUDY found that workers involved in cleaning up the nation’s largest oil spill were twice as likely to be diagnosed with asthma or experience asthma symptoms one to three years after the spill than non-workers.
Researchers hope discovery leads to potential treatments for mitochondrial diseases
Researchers from the National Institutes of Health have developed a three-dimensional structure that allows them to see how and where disease mutations on the twinkle protein can lead to mitochondrial diseases. The protein is involved in helping cells use energy our bodies convert from food. Prior to the development of this 3D structure, researchers only had models and were unable to determine how these mutations contribute to disease. Mitochondrial diseases are a group of inherited conditions that affect 1 in 5,000 people and have very few treatments.
“For the first time, we can map the mutations that are causing a number of these devastating diseases,” said lead author Amanda A. Riccio, Ph.D., and researcher in the National Institute of Environmental Health Sciences (NIEHS) Mitochondrial DNA Replication Group, which is part of NIH. “Clinicians can now see where these mutations lie and can use this information to help pinpoint causes and help families make choices, including decisions about having more children.”
The new findings will be particularly relevant for developing targeted treatments for patients who suffer from mitochondrial diseases such as progressive external ophthalmoplegia, a condition that can lead to loss of muscle functions involved in eye and eyelid movement; Perrault syndrome, a rare genetic disorder that can cause hearing loss; infantile-onset spinocerebellar ataxia, a hereditary neurological disorder; and hepatocerebral mitochondrial DNA (mtDNA) depletion syndrome, a hereditary disease that can lead to liver failure and neurological complications during infancy.
This image depicts the 3D structure that NIEHS researchers created of the twinkle protein. The researchers used cryo-electron microscopy and other techniques to show how disease mutations on the protein can lead to mitochondrial diseases.
Larger trials enrolling infants and children are underway in Mali and Kenya
One injection of a candidate monoclonal antibody (mAb) known as L9LS was found to be safe and highly protective in U.S. adults exposed to the malaria parasite, according to results from a National Institutes of Health Phase 1 clinical trial published in The New England Journal of Medicine. Additional clinical trials evaluating if L9LS can prevent malaria over six to 12 months against seasonal and perennial transmission are underway in infants and children in Mali and Kenya, where malaria is endemic. The trial was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH.
“These early clinical trial results demonstrating that a monoclonal antibody administered subcutaneously can protect people from malaria are highly encouraging,” said NIAID Director Anthony S. Fauci, M.D. “A one-time intervention that protects against malaria for six months to a year could significantly reduce morbidity and mortality among children in malaria-endemic regions and offer an effective preventive tool for health care workers, military personnel and travelers to these areas.”
Malaria is a mosquito-borne disease caused by Plasmodium parasites. The World Health Organization estimates that in 2020, about 240 million people had malaria and about 627,000 of them died. A disproportionate burden of malarial disease is seen in Sub-Saharan Africa, where children under age 5 account for approximately 80% of all malaria deaths. A vaccine to prevent malaria is now available; however, its variable efficacy underscores the need for new interventions that offer high-level protection against disease.
This image shows the lifecycle of the malaria parasite in a person.
Discovery sets the stage for development of new therapies to treat vitelliform macular dystrophy
Using a new imaging technique, researchers from the National Eye Institute have determined that retinal lesions from vitelliform macular dystrophy (VMD) vary by gene mutation. Addressing these differences may be key in designing effective treatments for this and other rare diseases. NEI is part of the National Institutes of Health.
“The NEI’s long-term investment in imaging technology is changing our understanding of eye diseases,” said NEI Director Michael F. Chiang, M.D. “This study is just one example of how improved imaging can reveal subtle details about pathology in a rare eye disease that can inform the development of therapeutics.”
VMD is an inherited genetic disease that causes progressive vision loss through degeneration of the light-sensing retina. Genes implicated in VMD include BEST1, PRPH2, IMPG1, and IMPG2. Depending on the gene and mutation, age of onset and severity vary widely. All forms of the disease have in common a lesion in the central retina (macula) that looks like an egg yolk and is a build-up of toxic fatty material called lipofuscin. VMD affects about 1 in 5,500 Americans and there is currently no treatment for this condition.
Johnny Tam, Ph.D., head of the NEI Clinical and Translational Imaging Unit, used multimodal imaging to evaluate the retinas of patients with VMD at the NIH Clinical Center. Tam’s multimodal imaging uses adaptive optics — a technique that employs deformable mirrors to improve resolution — to view live cells in the retina, including the light-sensing photoreceptors, retinal pigment epithelial (RPE) cells, and blood vessels in unprecedented detail.
Retina with egg-yolk-like lesion in a person with vitelliform macular dystrophy.
Loss of the protein pigment epithelium-derived factor (PEDF), which protects retinal support cells, may drive age-related changes in the retina, according to a new study in mice from the National Eye Institute (NEI). The retina is the light-sensitive tissue at the back of the eye, and aging-associated diseases of the retina, like age-related macular degeneration (AMD), can lead to blindness. This new finding could lead to therapies to prevent AMD and other aging conditions of the retina. The study was published in the International Journal of Molecular Sciences. NEI is part of the National Institutes of Health.
“People have called PEDF the ‘youth’ protein, because it is abundant in young retinas, but it declines during aging,” said Patricia Becerra, Ph.D., chief of NEI’s Section of Protein Structure and Function and senior author of the study. “This study showed for the first time that just removing PEDF leads to a host of gene changes that mimic aging in the retina.”
The retina is composed of layers of cells that function together to detect and process light signals, which the brain uses to generate vision. The retina’s light-sensing photoreceptors sit above the retinal pigment epithelium (RPE), a layer of support cells. The RPE nourishes photoreceptors and recycles pieces of the photoreceptor cells called 'outer segments,' which get used up and their tips shed each time photoreceptors detect light. If the RPE cannot provide recycled components of older outer segment tips back to photoreceptors, these cells lose their ability to make new segments, and eventually become unable to sense light. And without nutrients supplied by the RPE, photoreceptors die. In people with AMD or certain types of retinal dystrophies, senescence (aging) or death of RPE cells in the retina leads to vision loss.
RPE from mice without Serpin1 accumulate more lipids than wild-type mice. Super-resolution confocal microscopy of RPE tissue from wild-type (upper) and Serpin1-null (lower) mice. Detailed images on the right are magnified regions of the RPE tissue imaged on the left (dotted square area). RPE cell boundaries are stained in red, and accumulated lipids are stained in green.
Researchers from the National Cancer Institute, part of the National Institutes of Health, and their collaborators have discovered that people of European and African ancestries who were hospitalized for COVID-19 are more likely to carry a particular combination of genetic variants in a gene known as OAS1 than patients with mild disease who were not hospitalized. People with this combination of genetic variants also remain positive for SARS-CoV-2 infection longer. However, interferon treatment may reduce the severity of COVID-19 in people with these genetic factors. Interferons are a type of protein that can help the body’s immune system fight infection and other diseases, such as cancer.
The study appears July 14 in Nature Genetics.
These findings build on previous studies that have suggested that genetic factors, such as genetic variants affecting OAS antiviral proteins that facilitate the detection and breakdown of the SARS-CoV-2 virus, may influence the risk of SARS-CoV-2 infection.
The NCI researchers and their collaborators found that treatment of cells with an interferon decreased the viral load of SARS-CoV-2. The researchers also analyzed data from a clinical trial in which patients with COVID-19 who were not hospitalized were treated with the recombinant interferon pegIFN-λ1 and found that treatment improved viral clearance in all patients; those with the OAS1 risk variants benefitted the most. The results suggest that interferon treatment may improve COVID-19 outcomes and specifically in patients with certain OAS1 genetic variants who have impaired ability to clear infection.
NIH study of pregnant women confirms link with chemicals that could put pregnancy at risk
Pregnant women who were exposed to multiple phthalates during pregnancy had an increased risk of preterm birth, according to new research by the National Institutes of Health. Phthalates are chemicals used in personal care products, such as cosmetics, as well as in solvents, detergents, and food packaging.
After analyzing data from more than 6,000 pregnant women in the United States, researchers found that women with higher concentrations of several phthalate metabolites in their urine were more likely to deliver their babies preterm, which is delivering three or more weeks before a mother’s due date.
“Having a preterm birth can be dangerous for both baby and mom, so it is important to identify risk factors that could prevent it,” said Kelly Ferguson, Ph.D., an epidemiologist at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, and the senior author on the study published in the journal JAMA Pediatrics.
The image shows how a pregnant person may be exposed to phthalates by eating packaged foods and beverages or through personal care product use.
