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.
Plant molecule could be used to block postoperative incisional pain.
A promising approach to post-operative incision-site pain control uses a naturally occurring plant molecule called resiniferatoxin (RTX). RTX is found in Euphorbia resinifera, a cactus-like plant native to Morocco, which is 500 times more potent than the chemical that produces heat in hot peppers, and may help limit the use of opioid medication while in the hospital and during home recovery.
In a paper published online in Anesthesiology, the peer-reviewed medical journal of the American Society of Anesthesiologists, researchers found that RTX could be used to block postoperative incisional pain in an animal model. Many medical providers turn to opioids, such as morphine or fentanyl, for moderate to severe post-operative pain relief, but these often come with side effects that can interfere with recovery, including respiratory depression, inhibition of gut motility and constipation, nausea and vomiting. Prolonged use of opioids can produce tolerance and introduces the risk of misuse. RTX is not an opioid and does not act in the brain but rather on the nerve endings in the skin. Scientists found that it can be used to block pain from the surgical incision selectively for approximately 10 days.
Using fruit flies, NIH researchers provide molecular basis for theory of aging.
A shorter life may be the price an organism pays for coping with the natural assaults of daily living, according to researchers at the National Institutes of Health and their colleagues in Japan. The scientists used fruit flies to examine the relationship between lifespan and signaling proteins that defend the body against environmental stressors, such as bacterial infections and cold temperatures. Since flies and mammals share some of the same molecular pathways, the work may demonstrate how the environment affects longevity in humans.
Appearing in the Proceedings of the National Academy of Sciences, the research identified Methuselah-like receptor-10 (Mthl10), a protein that moderates how flies respond to inflammation. The finding provides evidence for one theory of aging, which suggests longevity depends on a delicate balance between proinflammatory proteins, thought to promote aging, and anti-inflammatory proteins, believed to prolong life. These inflammatory factors are influenced by what an organism experiences in its every day environment.
Corresponding author Stephen Shears, Ph.D., of the National Institute of Environmental Health Sciences (NIEHS) at NIH, explained that Mthl10 appears on the surface of insect cells and acts as the binding partner to a signaling molecule known as growth-blocking peptide (GBP). Once Mthl10 and GBP connect, they initiate the production of proinflammatory proteins, which, in turn, shortens the fly’s life. However, removing the Mthl10 gene makes the flies unable to produce Mthl10 protein and prevents the binding of GBP to cells. As a result, the flies experienced low levels of inflammation and longer lifespans.
"Fruit flies without Mthl10 live up to 25 percent longer," Shears said. "But, they exhibit higher death rates when exposed to environmental stressors."
The binding of GBP to Mthl10 promotes inflammation, which decreases the lifespan of a fruit fly. In contrast, the removal of GBP’s binding partner Mthl10, produces less inflammation and increases the lifespan of the fly.
Researchers find target to protect hearing during chemotherapy treatment.
Scientists have found a new way to explain the hearing loss caused by cisplatin, a powerful drug used to treat many forms of cancer. Using a highly sensitive technique to measure and map cisplatin in mouse and human inner ear tissues, researchers found that forms of cisplatin build up in the inner ear. They also found a region in the inner ear that could be targeted for efforts to prevent hearing loss from cisplatin. The study is published in Nature Communications, and was supported by the National Institute on Deafness and other Communications Disorders (NIDCD), part of the National Institutes of Health.
Cisplatin and similar platinum-based drugs are prescribed for an estimated 10 to 20 percent of all cancer patients. The NIH’s National Cancer Institute supported research that led to the 1965 discovery of cisplatin and continued development leading to its success as an essential weapon in the battle against cancer. The drugs cause permanent hearing loss in 40 to 80 percent of adult patients and at least half of children who receive the drug. The new findings help explain why cisplatin is so toxic to the inner ear, and why hearing loss gets worse after each treatment, can occur long after treatment, and is more severe in children than adults.
Cisplatin (appearing in green) in the stria vascularis of a mouse inner ear.
Scientists have identified differences in a group of genes they say might help explain why some people need a lot more sleep — and others less — than most. The study, conducted using fruit fly populations bred to model natural variations in human sleep patterns, provides new clues to how genes for sleep duration are linked to a wide variety of biological processes.
Researchers say a better understanding of these processes could lead to new ways to treat sleep disorders such as insomnia and narcolepsy. Led by scientists with the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, the study will be published on Dec. 14 in PLOS Genetics.
“This study is an important step toward solving one of the biggest mysteries in biology: the need to sleep,” says study leader Susan Harbison, Ph.D., an investigator in the Laboratory of Systems Genetics at NHLBI. “The involvement of highly diverse biological processes in sleep duration may help explain why the purpose of sleep has been so elusive.”
Graph showing sleep duration (in minutes) of wild fruit flies—long sleepers, normal sleepers, and short sleepers—artificially bred across 13 generations.
Vaccine developed by NIH scientists shows promise in Phase 1 testing.
Results from two Phase 1 clinical trials show an experimental Zika vaccine developed by government scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is safe and induces an immune response in healthy adults. The findings will be published on Dec. 4 in The Lancet. NIAID is currently leading an international effort to evaluate the investigational vaccine in a Phase 2/2b safety and efficacy trial.
“Following early reports that Zika infection during pregnancy can lead to birth defects, NIAID scientists rapidly created one of the first investigational Zika vaccines using a DNA-based platform and began initial studies in healthy adults less than one year later,” said NIAID Director Anthony S. Fauci, M.D. “NIAID has begun Phase 2 testing of this candidate to determine if it can prevent Zika virus infection, and the promising Phase 1 data published today support its continued development.”
Investigators from NIAID’s Vaccine Research Center (VRC) and Laboratory of Viral Diseases, part of the Division of Intramural Research, developed the investigational vaccine, which includes a small, circular piece of DNA called a plasmid. Scientists inserted genes into the plasmid that encode two proteins found on the surface of the Zika virus. After the vaccine is injected into muscle, the body produces proteins that assemble into particles that mimic the Zika virus and trigger the body to mount an immune response.
Allergens are widespread, but highly variable in U.S. homes, according to the nation’s largest indoor allergen study to date. Researchers from the National Institutes of Health report that over 90 percent of homes had three or more detectable allergens, and 73 percent of homes had at least one allergen at elevated levels. The findings were published November 30 in the Journal of Allergy and Clinical Immunology.
“Elevated allergen levels can exacerbate symptoms in people who suffer from asthma and allergies, so it is crucial to understand the factors that contribute,” said Darryl Zeldin, M.D., senior author and scientific director at the National Institute of Environmental Health Sciences (NIEHS), which is part of NIH.
Using data from the 2005-2006 National Health and Nutrition Examination Survey (NHANES), the researchers studied levels of eight common allergens – cat, dog, cockroach, mouse, rat, mold, and two types of dust mite allergens – in the bedrooms of nearly 7,000 U.S. homes.
Factors contributing to elevated bedroom allergen levels include presence of pets and pests, type of housing, and living in rural areas. Individual allergens vary by geographic area.
NIH-supported study provides evidence for implementing approach broadly.
A study published today in the New England Journal of Medicine provides real-world evidence that implementing a combination of proven HIV prevention measures across communities can substantially reduce new HIV infections in a population.
Investigators found that HIV incidence dropped by 42 percent among nearly 18,000 people in Rakai District, Uganda, during a seven-year period in which the rates of HIV treatment and voluntary medical male circumcision increased significantly.
The HIV prevention strategy whose impact was observed in the study is based on earlier findings by the National Institutes of Health and others demonstrating the protective effect of voluntary medical male circumcisionfor HIV-uninfected men and of HIV-suppressing antiretroviral therapy (ART) for halting sexual transmission of the virus to uninfected partners. The strategy is also based on studies showing that changes in sexual behavior, such as having only one sexual partner, can help prevent HIV infection.
A research assistant draws blood for HIV testing from a participant in the Rakai Community Cohort Study. Credit: Rakai Health Sciences Program
Population study finds higher risk of psychiatric hospitalization among daughters of female evacuees.
Mental illness associated with early childhood adversity may be passed from generation to generation, according to a study of adults whose parents evacuated Finland as children during World War II. The study was conducted by researchers at the National Institutes of Health, Uppsala University in Sweden, and Helsinki University in Finland. It appears in JAMA Psychiatry.
The research team found that daughters of female evacuees had the same high risk for mental health disorders as their mothers, even though they did not experience the same adversity. The study could not determine why the higher risk for mental illness persisted across generations. Possible explanations include changes in the evacuees’ parenting behavior stemming from their childhood experience or epigenetic changes — chemical alterations in gene expression, without any changes to underlying DNA.
“Many studies have shown that traumatic exposures during pregnancy can have negative effects on offspring,” said study author Stephen Gilman, Sc.D., of the Division of Intramural Population Health Research at the Eunice Kennedy Shriver National Institute of Child Health and Human Development. “Here, we found evidence that a mother’s childhood traumatic exposure — in this case separation from family members during war — may have long-lasting health consequences for her daughters.”
Tick bites likely lead to the unusual, misdiagnosed allergy.
While rare, some people experience recurrent episodes of anaphylaxis — a life-threatening allergic reaction that causes symptoms such as the constriction of airways and a dangerous drop in blood pressure — for which the triggers are never identified. Recently, researchers at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, found that some patients’ seemingly inexplicable anaphylaxis was actually caused by an uncommon allergy to a molecule found naturally in red meat. They note that the allergy, which is linked to a history of a specific type of tick bite, may be difficult for patients and health care teams to identify.
As the researchers describe in their article published in Allergy, six of the 70 study participants evaluated for unexplained frequent anaphylaxis tested positive for an allergy to galactose-α-1,3-galactose, or alpha-gal, a sugar molecule found in beef, pork, lamb and other red meats. The six adult male participants all had IgE antibodies — immune proteins associated with allergy — to alpha-gal in their blood. After implementing diets free of red meat, none of them experienced anaphylaxis in the 18 months to 3 years during which they were followed.
An adult female Lone Star tick climbs on a plant. Bites from the juvenile form of this species, sometimes called seed ticks, are linked to the development of red meat allergy.
National Institutes of Health scientists and collaborators at Case Western Reserve University School of Medicine, Cleveland, have detected abnormal prion protein in the skin of nearly two dozen people who died from Creutzfeldt-Jakob disease (CJD). The scientists also exposed a dozen healthy mice to skin extracts from two of the CJD patients, and all developed prion disease. The study results, published in Science Translational Medicine, raise questions about the possible transmissibility of prion diseases via medical procedures involving skin, and whether skin samples might be used to detect prion disease. Researchers from NIH’s National Institute of Allergy and Infectious Diseases (NIAID) were co-leaders of the study, which included multiple collaborating groups. They stress that the prion-seeding potential found in skin tissue is significantly less than what they have found in studies using brain tissue.
CJD is an incurable — and ultimately fatal — transmissible, neurodegenerative disorder in the family of prion diseases. Prion diseases originate when normally harmless prion protein molecules become abnormal and gather in clusters and filaments in the human body and brain. The reasons for this process are not fully understood. The accumulation of these clusters has been associated with tissue damage that leaves sponge-like holes in the brain. Human prion diseases include fatal insomnia; kuru; Gerstmann-Straussler-Scheinker syndrome; and variant, familial and sporadic CJD. Sporadic CJD is the most common human prion disease, affecting about one in one million people annually worldwide. Other prion diseases include scrapie in sheep; chronic wasting disease in deer, elk and moose; and bovine spongiform encephalopathy, or mad cow disease, in cattle.
The brain of one patient who died from sporadic Creutzfeldt-Jacob disease (sCJD) appears nearly identical to the brain of a mouse inoculated with infectious prions taken from the skin of patients who died from sCJD.
