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.
IRP study also suggests that handling a cell phone doubles teen driver crash risk
Teenagers who reach for objects, such as food or makeup, while driving increase their risk of crashing nearly seven times, according to researchers at the National Institutes of Health. Their study, which appears in the American Journal of Preventative Medicine, also found that manually dialing, texting or browsing the web on a phone while driving doubled a teen’s crash risk.
Motor vehicle crashes are the leading cause of death and disabilities among drivers aged 15 to 20 years, according to the National Highway Traffic Safety Administration. The current study is the first to use real-time driving data to quantify the extent to which visual inattention — the amount of time a teen’s eyes shift from the road to various distractions — contributes to the risk of a crash.
Researchers followed 82 newly licensed teen drivers in Virginia over a one-year period, equipping their vehicles with cameras and GPS technology to track the driver’s activity and environment. After one year, 43 of the drivers did not experience a crash, while 25 had one crash and 14 had two or more crashes. Using six-second videos of driver behavior prior to a crash, researchers calculated that for every second that a teen’s eyes were off the road, the risk of a crash increased by 28 percent regardless of the type of distraction. Teens manually using a cell phone doubled their odds of crashing. Teens who were reaching for something while driving increased their risk nearly sevenfold, which researchers attributed to a combination of distractions, including taking their eyes off the road and their hands off the wheel.
IRP scientists use epigenetics to help predict disease development
Biologic age, a DNA-based estimate of a person’s age, is associated with future development of breast cancer, according to scientists at the National Institutes of Health. Biologic age was determined by measuring DNA methylation, a chemical modification to DNA that is part of the normal aging process. The study showed for every five years a woman’s biologic age was older than her chronologic or actual age, known as age acceleration, she had a 15 percent increase in her chance of developing breast cancer. The study was published online Feb. 22 in the Journal of the National Cancer Institute.
Scientists from the National Institute of Environmental Health Sciences (NIEHS), part of NIH, speculate that biologic age may be tied to environmental exposures. If so, it may be a useful indicator of disease risk. They used three different measures, called epigenetic clocks, to estimate biologic age. These clocks measure methylation found at specific locations in DNA. Researchers use these clocks to estimate biologic age, which can then be compared to chronologic age.
The researchers used DNA from blood samples provided by women enrolled in the NIEHS-led Sister Study, a group of more than 50,000 women in the U.S. and Puerto Rico. The study was specifically designed to identify environmental and genetic risk factors for breast cancer. The research team measured methylation in a subset of 2,764 women, all of whom were cancer-free at the time of blood collection.
"We found that if your biologic age is older than your chronologic age, your breast cancer risk is increased. The converse was also true. If your biologic age is younger than your chronologic age, you may have decreased risk of developing breast cancer," said corresponding author Jack Taylor, M.D., Ph.D., head of the NIEHS Molecular and Genetic Epidemiology Group. "However, we don’t yet know how exposures and lifestyle factors may affect biologic age or whether this process can be reversed."
If a woman’s biologic age is older than her chronologic age, she has an increased risk of developing breast cancer.
IRP clinical study results suggest the drug could help protect skin and prevent vision problems
A small pilot clinical study at the National Eye Institute (NEI) suggests that the drug nitisinone increases melanin production in some people with oculocutaneous albinism type 1B (OCA-1B), a rare genetic disease that causes pale skin and hair and poor vision. Increased melanin could help protect people with the condition against the sun’s UV rays and promote the development of normal vision. Study results were published in JCI Insight. NEI is part of the National Institutes of Health (NIH).
“Because the greatest vision problems for people with albinism occur during the early development of the eye, our eventual goal is to work with infants,” said Brian Brooks, M.D., Ph.D., clinical director at NEI and lead author of the study. “The purpose of this pilot study was to explore whether nitisinone is safe and whether we could pick up a signal that the drug works.”
Study participant has darker hair after six months on nitisinone (right), compared to baseline (left).
FDA- and NIH-funded study finds unexpected sensory variant exclusive to African-Americans
A genetic variant found only in people of African descent significantly increases a smoker’s preference for cigarettes containing menthol, a flavor additive. The variant of the MRGPRX4 gene is five to eight times more frequent among smokers who use menthol cigarettes than other smokers, according to an international group of researchers supported by the U.S. Food and Drug Administration and the National Institutes of Health. The multiethnic study is the first to look across all genes to identify genetic vulnerability to menthol cigarettes. The paper was published online in the journal PLOS Genetics on Feb. 15.
Menthol provides a minty taste and a cooling or soothing sensation, and plays a particularly troubling role in U.S. cigarette smoking patterns. According to the FDA, nearly 20 million people in the United States smoke menthol cigarettes, which are particularly popular among African-American smokers and teen smokers. In the U.S., 86 percent of African-American smokers use menthol cigarettes, compared to less than 30 percent of smokers of European descent. In addition, menthol cigarettes may be harder to quit than other cigarettes.
Although not originally the focus of the study, researchers also uncovered clues as to how menthol may reduce the irritation and harshness of smoking cigarettes.
“This study sheds light on the molecular mechanisms of how menthol interacts with the body,” said Andrew Griffith, M.D., Ph.D., scientific director and acting deputy director of NIH’s National Institute on Deafness and Other Communications Disorders (NIDCD). “These results can help inform public health strategies to lower the rates of harmful cigarette smoking among groups particularly vulnerable to using menthol cigarettes.”
The research team, led by Dennis Drayna, Ph.D., chief of the Section on Genetics of Communication Disorders at the NIDCD, conducted detailed genetic analyses on 1,300 adults. In the initial analyses, researchers at the University of Texas Southwestern Medical Center, Dallas (UT Southwestern), used data from a multiethnic, population-based group of smokers from the Dallas Heart Study and from an African-American group of smokers from the Dallas Biobank. In conjunction with researchers from the Schroeder Institute® for Tobacco Research, Washington, D.C., the scientists further confirmed their findings in a group of African-American smokers enrolled in the Washington, D.C., Tobacco QuitlineTM.
Researchers measured pain’s impact on normal work activities, people’s health status, and health care use
Prompted by a call from the National Academy of Medicine, then the Institute of Medicine, for improved national data on pain, a recent study provides new insights concerning pain trends and opioid use for pain management. Researchers used data from the Medical Expenditure Panel Survey (MEPS) to examine the impact of pain-related interference, a measure of pain’s impact on normal work activities, on people’s health status and health care use. MEPS is a nationally representative survey of the U.S. civilian, noninstitutionalized population.
Researchers showed that the number of U.S. adults age 18 and older suffering from at least one painful health condition increased substantially from 120.2 million (32.9 percent) in 1997/1998 to 178 million (41 percent) in 2013/2014. Furthermore, the use of strong opioids, like fentanyl, morphine, and oxycodone, for pain management among adults with severe pain-related interference more than doubled from 4.1 million (11.5 percent) in 2001/2002 to 10.5 million (24.3 percent) in 2013/2014. These are the findings of a comprehensive analysis of 18-year trends showing changes in the overall rates of noncancer pain prevalence and management. The full study, conducted by the National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health; Social & Scientific Systems, Inc., Silver Spring, Maryland; and Yale University School of Medicine, New Haven, Connecticut; was published in the Journal of Pain.
“We took a unique approach with this study by simultaneously examining long-term trends in the overall prevalence of noncancer pain in the U.S., the impact of this pain, and health care use attributable directly to pain management,” says Richard L. Nahin, Ph.D., first author on the study and NCCIH lead epidemiologist. “To address these gaps, we used data from MEPS to identify trends between 1997 and 2014.”
National Eye Institute scientists led a collaborative study and zeroed in on genes associated with age-related macular degeneration (AMD), a leading cause of vision loss and blindness among people age 65 and older. These findings provide a more expanded and in-depth picture of the genetic contributions to AMD, and they present new pathways for treatment development. The study was published Feb. 11 in Nature Genetics.
“If we were conducting a criminal investigation, prior research would have localized different crime syndicates to 52 streets within 34 zip codes. These latest findings identify actual suspects — direct targets that we can more closely investigate,” said the study’s lead investigator Anand Swaroop, Ph.D., chief of the Neurobiology-Neurodegeneration and Repair Laboratory at NEI, which is part of the National Institutes of Health.
Previously, Swaroop and colleagues had compared populations of people with and without AMD and identified 34 small genomic regions — called loci — and 52 genetic variants within these loci that were significantly associated with AMD. “However, as with other common and complex diseases, most of the variants turned out not to be present in protein-coding regions of the genome, leaving us to wonder how they were having a biological effect on AMD,” said Swaroop.
AMD causes the loss of cell function in the macula, the area of the retina required for seeing details in one’s central area of vision. AMD is a leading cause of vision loss and blindness among people age 65 and older.
Researchers have found that treating psoriasis, a chronic inflammatory skin disease, with biologic drugs that target immune system activity can reduce the early plaque buildup that clogs arteries, restricts blood flow, and leads to heart attacks and stroke. The findings highlight how immunotherapies that treat inflammatory conditions might play a role in the reduction of cardiovascular disease risks. The study, funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, appears online today in the journal Cardiovascular Research.
“Classically a heart attack is caused by one of five risk factors: diabetes, hypertension, high cholesterol, family history, or smoking,” said Nehal N. Mehta, M.D., head of the Lab of Inflammation and Cardiometabolic Diseases at NHLBI. “Our study presents evidence that there is a sixth factor, inflammation; and that it is critical to both the development and the progression of atherosclerosis to heart attack.”
Longitudinal and cross-section views of left anterior descending artery (A) before treatment with biologic therapy and (B) after one year of biologic therapy.
The salivary glands of some tick species could become important research tools for studying how viruses are transmitted from ticks to mammals, and for developing preventive medical countermeasures. Tick salivary glands usually block transmission, but a new study conducted by scientists at the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health focuses on the role of salivary glands in spreading flaviviruses from black-legged ticks (Ixodes scapularis) to mammals. The new study, published in the journal mBio, advances the researchers’ work published in 2017 that established cultured tick organs as a model for flavivirus infection.
Flaviviruses include dengue virus, Zika virus, West Nile virus, yellow fever virus, Powassan virus and several other viruses. Powassan is the only endemic flavivirus spread by ticks in North America, where it is considered a re-emerging virus. Physicians in the United States have reported roughly 100 cases of disease in the past decade, half of them in 2016-17. Powassan virus disease occurs primarily in northeastern states and the Great Lakes region. Though disease caused by Powassan virus is rare — most people who become infected with Powassan virus do not develop any symptoms — the virus can be transmitted very rapidly. Within 15 minutes, an infected tick can transmit the virus to a person or other mammal on which it is feeding. Symptoms of Powassan virus disease can include fever, headache, vomiting, weakness, confusion, loss of coordination, speech difficulties, and seizures. If the virus infects the central nervous system, it can cause brain inflammation and meningitis. Debilitating long-term neurological problems or even death may occur.
This confocal microscope image shows a cross section of a tick salivary gland infected with Langat virus (green). Two rounded structures on the right, called acini, are shown attached to a duct (yellow). The lower acinus is infected, as denoted by the green fluorescent signal.
The investigational Ebola treatment mAb114 is safe, well-tolerated, and easy to administer, according to findings from an early-stage clinical trial published in The Lancet. Eighteen healthy adults received the monoclonal antibody as part of a Phase 1 clinical trial that began in May 2018 at the National Institutes of Health (NIH) Clinical Center in Bethesda, Maryland. The National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC), part of NIH, developed the investigational treatment and conducted and sponsored the clinical trial.
The investigational treatment is currently being offered to Ebola patients in the Democratic Republic of the Congo (DRC) under compassionate use and as part of a Phase 2/3 clinical trial of multiple investigational treatments. mAb114, a single monoclonal antibody, binds to the core receptor binding domain of the Zaire ebolavirus surface protein, preventing the virus from infecting human cells. Scientists isolated the antibody from a human survivor of the 1995 Ebola outbreak in Kikwit, DRC. Prior studies showed that mAb114 can protect monkeys from lethal Ebola virus disease when given as late as five days after infection.
After multiplying inside a host cell, the string-like Ebola virus is emerging to infect more cells. Ebola is a rare, often fatal disease that occurs primarily in tropical regions of sub-Saharan Africa.
New tool that uses DNA sequencing could improve transplant outcomes and save lives
Researchers have developed a simple blood test that can detect when a newly transplanted lung is being rejected by a patient, even when no outward signs of the rejection are evident. The test could make it possible for doctors to intervene faster to prevent or slow down so-called chronic rejection — which is severe, irreversible, and often deadly — in those first critical months after lung transplantation. Researchers believe this same test might also be useful for monitoring rejection in other types of organ transplants. The work was funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.
The study’s findings were published Jan. 22 in EBioMedicine, a publication of The Lancet.
“This test solves a long-standing problem in lung transplants: detection of hidden signs of rejection,” said Hannah Valantine, M.D., co-leader of the study and lead investigator of the Laboratory of Organ Transplant Genomics in the Cardiovascular Branch at NHLBI. “We’re very excited about its potential to save lives, especially in the wake of a critical shortage of donor organs.”
This illustration depicts a new blood test that can identify early signs of lung transplant rejection using DNA markers from the organ donor.
