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.
In a new study, researchers developed a gene expression predictor that can indicate whether melanoma in a specific patient is likely to respond to treatment with immune checkpoint inhibitors, a novel type of immunotherapy. The predictor was developed by Noam Auslander, Ph.D., with other researchers in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues at Harvard University, Cambridge, Massachusetts; the University of Pennsylvania, Philadelphia; and the University of Maryland, College Park. The study was published Aug. 20, 2018 in Nature Medicine.
“There is a critical need to be able to predict how cancer patients will respond to this type of immunotherapy,” said Eytan Ruppin, M.D., Ph.D., of NCI’s newly established Cancer Data Science Laboratory, who led the study. “Being able to predict who is highly likely to respond and who isn’t will enable us to more accurately and precisely guide patients’ treatment.”
Treatment with checkpoint inhibitors is effective for some patients with late-stage melanoma and certain other types of cancer. However, not all patients with melanoma respond to this treatment, and it can have considerable side effects. But developing a predictor of response has been challenging, partly because of the limited number of patients who have received this relatively new form of treatment.
IRP analysis suggests early screening could allow for lifestyle changes before condition develops
A blood test conducted as early as the 10th week of pregnancy may help identify women at risk for gestational diabetes, a pregnancy-related condition that poses potentially serious health risks for mothers and infants, according to researchers at the National Institutes of Health and other institutions. The study appears in Scientific Reports.
Gestational diabetes occurs only in pregnancy and results when the level of blood sugar, or glucose, rises too high. Gestational diabetes increases the mother’s chances for high blood pressure disorders of pregnancy and the need for cesarean delivery, and the risk for cardiovascular disease and type 2 diabetes later in life. For infants, gestational diabetes increases the risk for large birth size. Unless they have a known risk factor, such as obesity, women typically are screened for gestational diabetes between 24 and 28 weeks of pregnancy.
In the current study, researchers evaluated whether the HbA1c test (also called the A1C test), commonly used to diagnose type 2 diabetes, could identify signs of gestational diabetes in the first trimester of pregnancy. The test approximates the average blood glucose levels over the previous 2 or 3 months, based on the amount of glucose that has accumulated on the surface of red blood cells. According to the authors, comparatively few studies have examined whether the HbA1c test could help identify the risk for gestational diabetes, and these studies have been limited to women already at high risk for the condition. The test is not currently recommended to diagnose gestational diabetes at any point in pregnancy.
IRP study reveals prevalence of and risk factors for phantom odor perception
Imagine the foul smell of an ash tray or burning hair. Now imagine if these kinds of smells were present in your life, but without a source. A new study finds that 1 in 15 Americans (or 6.5 percent) over the age of 40 experiences phantom odors. The study, published in JAMA Otolaryngology-Head and Neck Surgery, is the first in the U.S. to use nationally representative data to examine the prevalence of and risk factors for phantom odor perception. The study could inform future research aiming to unlock the mysteries of phantom odors.
The study was led by Kathleen Bainbridge, Ph.D., of the Epidemiology and Biostatistics Program at the National Institute on Deafness and Other Communication Disorders (NIDCD), part of the National Institutes of Health. Bainbridge and her team used data from 7,417 participants over 40 years of age from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). The NHANES data were collected by the National Center for Health Statistics, which is part of the Centers for Disease Control and Prevention; data collection was partly funded by the NIDCD.
"Problems with the sense of smell are often overlooked, despite their importance. They can have a big impact on appetite, food preferences, and the ability to smell danger signals such as fire, gas leaks, and spoiled food,” said Judith A. Cooper, Ph.D., acting director of the NIDCD.
In the past 15 years, two outbreaks of severe respiratory disease were caused by coronaviruses transmitted from animals to humans. In 2003, SARS-CoV (severe acute respiratory syndrome coronavirus) spread from civets to infect more than 8,000 people, leading to a year-long global public health emergency. MERS-CoV (Middle East respiratory syndrome coronavirus), first identified in 2012, consistently jumps from dromedary camels to people, resulting in periodic outbreaks with a roughly 35 percent fatality rate. Evidence suggests that both viruses originated in bats before transmitting to civets and camels, respectively. While many other coronaviruses in nature are not known to infect people, MERS-CoV and SARS-CoV are notable for their ability to infect a variety of different species, including humans.
New research published in Cell Reports from scientists at the National Institute of Allergy and Infectious Diseases (NIAID) shows how MERS-CoV can adapt to infect cells of a new species, which suggests that other coronaviruses might be able to do the same.
This illustration shows the bat species used in the study, Desmodus rotundus, or vampire bat, and representations of MERS-CoV (purple) interacting with host receptor DPP4 (gold).
For the first time, scientists have shown that in certain people living with HIV, a type of antibody called immunoglobulin G3 (IgG3) stops the immune system’s B cells from doing their normal job of fighting pathogens. This phenomenon appears to be one way the body tries to reduce the potentially damaging effects of immune-system hyperactivity caused by the presence of HIV, according to the investigators, but in so doing, it also impairs normal immune function.
The investigators made their discovery by analyzing blood samples from 83 HIV-uninfected, anonymous donors and 108 people who were living with HIV at various stages of infection. The people living with HIV came from a variety of racial and ethnic backgrounds. Some of these people were being treated for their infection, while others had not yet begun therapy.
Colorized scanning electron micrograph of a B cell from a human donor.
Elective induction at 39 weeks also linked to lower risk of maternal high blood pressure disorders
Healthy first-time mothers whose labor was induced in the 39th week of pregnancy were less likely to deliver by cesarean section, compared to those who waited for labor to begin naturally, according to a study funded by the National Institutes of Health. Researchers also found that infants born to women induced at 39 weeks were no more likely to experience stillbirth, newborn death or other severe complications, compared to infants born to uninduced women. The study results, which were presented earlier in brief form, now appear in detail in the New England Journal of Medicine.
“Prior to this study, there was concern that induction of labor would increase the chance of cesarean delivery,” said study author Uma M. Reddy, M.D., of the Pregnancy and Perinatology Branch of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). “Our analysis suggests that elective induction at 39 weeks is associated with a lower rate of cesarean delivery and does not increase the risk of major complications for newborns.”
Membrane-bound virus clusters provide promising target for the treatment of gastroenteritis, other diseases
Researchers have found that a group of viruses that cause severe stomach illness — including the one famous for widespread outbreaks on cruise ships — get transmitted to humans through membrane-cloaked “virus clusters” that exacerbate the spread and severity of disease. Previously, it was believed that these viruses only spread through individual virus particles. The discovery of these clusters, the scientists say, marks a turning point in the understanding of how these viruses spread and why they are so infectious. This preliminary work could lead to the development of more effective antiviral agents than existing treatments that mainly target individual particles.
The researchers studied norovirus and rotavirus — hard-to-treat viruses that are the most common cause of stomach illness, or gastroenteritis, and that afflicts millions of people each year. The viruses cause symptoms ranging from diarrhea to abdominal pain and can sometimes result in death, particularly among young children and the elderly. Their highly contagious nature has led to serious outbreaks in crowded spaces throughout many communities; most notably in cruise ships, daycare centers, classrooms, and nursing homes. Fortunately, vaccines against rotavirus are now available and are routinely given to babies in the United States.
“This is a really exciting finding in the field of virology because it reveals a mode of virus spread that has not been observed among humans and animals,” said study leader Nihal Altan-Bonnet, Ph.D., senior investigator and head of the Laboratory of Host-Pathogen Dynamics at the National Heart, Lung, and Blood Institute (NHLBI). “We hope that it will provide new clues to fighting a wide range of diseases involving many types of viruses, including those that cause gastrointestinal illnesses, heart inflammation, certain respiratory illnesses, and even the common cold.”
The National Institutes of Health’s Clinical Center has made a large-scale dataset of CT images publicly available to help the scientific community improve detection accuracy of lesions. While most publicly available medical image datasets have less than a thousand lesions, this dataset, named DeepLesion, has over 32,000 annotated lesions identified on CT images.
The images, which have been thoroughly anonymized, represent 4,400 unique patients, who are partners in research at the NIH.
Once a patient steps out of a CT scanner, the corresponding images are sent to a radiologist to interpret. Radiologists at the Clinical Center then measure and mark clinically meaningful findings with an electronic bookmark tool. Similar to a physical bookmark, radiologists save their place and mark significant findings to be able to come back to at a later time. These bookmarks are complex – they provide arrows, lines, diameters, and text that can tell the exact location and size of a lesion so experts can identify growth or new disease.
Approach could improve understanding of immune system recovery in people treated for HIV infection
Findings from an animal study suggest that a non-invasive imaging technique could, with further development, become a useful tool to assess immune system recovery in people receiving treatment for HIV infection. Researchers used single-photon emission computed tomography (SPECT) and a CD4-specific imaging probe to assess immune system changes throughout the bodies of macaques infected with SIV, a simian form of HIV, following initiation and interruption of antiretroviral therapy (ART). They evaluated pools of CD4+T cells, the main cell type that HIV infects and destroys, in tissues such as lymph nodes, spleen and gut.
Their findings illustrate that CD4+ T-cell levels in the blood — a measure of immune system health in people living with HIV — often fail to fully reflect the situation in tissues. A low blood CD4+ T-cell level indicates an immune system weakened by HIV, and the level generally increases when ART is started and the immune system begins to recover. The new research, led by scientists at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, delineates the complexity of the immune recovery process at the level of different tissues.
Findings could inform the development of new antimalarial drugs
The vacuole, a compartment inside human red blood cells in which malaria parasites reproduce and develop, takes on a distinct spherical shape just minutes before its membrane ruptures, leading to the release of parasites into the blood stream, according to researchers at the National Institutes of Health and other institutions. Their study appears in Cellular Microbiology.
The researchers, working with red blood cells from healthy donors, were able to chemically block the sequence of events leading to this rounding of the vacuole. They note that targeting this sequence could inform new treatment strategies against Plasmodium falciparum, the species of malaria parasite that causes the most deaths worldwide and, in several areas, has become drug-resistant.
To track the rounding sequence under a microscope, researchers dyed the membrane of the vacuole with a substance that gives off green light. About 10 minutes before the membrane ruptured, the vacuole morphed from a lumpy, uneven shape to a sphere. Previous studies have shown that malaria parasites use calcium to trigger the biochemical reactions needed for their release from the cell. When the researchers treated the cells with a compound that blocks calcium’s effect, the vacuoles couldn’t transition to the spherical form, trapping the parasites inside the cell.
