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.
A study from the National Institutes of Health confirms that neurofilament light chain as a blood biomarker can detect brain injury and predict recovery in multiple groups, including professional hockey players with acute or chronic concussions and clinic-based patients with mild, moderate, or severe traumatic brain injury. The research was conducted by scientists at the NIH Clinical Center, Bethesda, Maryland, and published in the July 8, 2020, online issue of Neurology.
After a traumatic brain injury, neurofilament light chain breaks away from neurons in the brain and collects in the cerebrospinal fluid (CSF). The scientists confirmed that neurofilament light chain also collects in the blood in levels that correlate closely with the levels in the CSF. They demonstrated that neurofilament light chain in the blood can detect brain injury and predict recovery across all stages of traumatic brain injury.
“Currently, there are no validated blood-based biomarkers to provide an objective diagnosis of mild traumatic brain injury or to predict recovery,” said Leighton Chan, M.D., M.P.H., chief of the Rehabilitation Medicine Department at the NIH Clinical Center. “Our study reinforces the need and a way forward for a non-invasive test of neurofilament light chain to aid in the diagnosis of patients and athletes whose brain injuries are often unrecognized, undiagnosed or underreported."
Neurofilament light chain on a neuron. Image credit: Pashtun Shahim, M.D., Ph.D.
Large-scale study of U.S. teens shows associations between outdoor, artificial light at night and health outcomes
Research shows that adolescents who live in areas that have high levels of artificial light at night tend to get less sleep and are more likely to have a mood disorder relative to teens who live in areas with low levels of night-time light. The research was funded by the National Institute of Mental Health (NIMH), part of the National Institutes of Health, and is published in JAMA Psychiatry.
“These findings illustrate the importance of joint consideration of both broader environmental-level and individual-level exposures in mental health and sleep research,” says study author Diana Paksarian, Ph.D., a postdoctoral research fellow at NIMH.
Daily rhythms, including the circadian rhythms that drive our sleep-wake cycles, are thought to be important factors that contribute to physical and mental health. The presence of artificial light at night can disrupt these rhythms, altering the light-dark cycle that influences hormonal, cellular, and other biological processes. Researchers have investigated associations among indoor artificial light, daily rhythms, and mental health, but the impact of outdoor artificial light has received relatively little attention, especially in teens.
In this study, Paksarian, Kathleen Merikangas, Ph.D., senior investigator and chief of the Genetic Epidemiology Research Branch at NIMH, and coauthors examined data from a nationally representative sample of adolescents in the United States, which was collected from 2001 to 2004 as part of the National Comorbidity Survey Adolescent Supplement (NCS-A). The dataset included information about individual-level and neighborhood-level characteristics, mental health outcomes, and sleep patterns for a total of 10,123 teens, ages 13 to 18 years old.
Iodine solutions are commonly used as disinfectants to prepare the skin for surgical or other procedures
Exposure to iodine used for medical procedures in a neonatal intensive care unit (NICU) may increase an infant’s risk for congenital hypothyroidism (loss of thyroid function), suggests a study by researchers at the National Institutes of Health and other institutions. The authors found that infants diagnosed with congenital hypothyroidism following a NICU stay had higher blood iodine levels on average than infants who had a NICU stay but had normal thyroid function. Their study appears in The Journal of Nutrition.
“Limiting iodine exposure among this group of infants whenever possible may help lower the risk of losing thyroid function,” said the study’s first author, James L. Mills, M.D., of the Epidemiology Branch at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).
Congenital hypothyroidism is a partial or complete loss of thyroid function. The thyroid, located in the throat, makes iodine-containing hormones that regulate growth, brain development and the rate of chemical reactions in the body. Treatment consists of thyroid hormone therapy and must begin within four weeks after birth or permanent intellectual disability may result.
National Institutes of Health Director Francis S. Collins, M.D., Ph.D., has selected Shannon N. Zenk, Ph.D., M.P.H., R.N., F.A.A.N., as director of NIH’s National Institute of Nursing Research (NINR). A registered nurse and leading nurse researcher, Dr. Zenk is currently Nursing Collegiate Professor in the Department of Population Health Nursing Science at the University of Illinois at Chicago (UIC) College of Nursing, and a fellow at the UIC Institute for Health Research and Policy. She is expected to begin her new role as the NINR director in early fall. NINR supports and conducts basic and clinical research that spans and integrates the behavioral and biological sciences and develops the scientific basis for clinical practice.
“Dr. Zenk’s diverse and original research experience paired with her expertise as a nurse educator make her an ideal choice to lead NIH’s efforts in nursing science,” said Dr. Collins. “I am delighted to have her join the NIH leadership team in the fall. I also want to recognize Tara A. Schwetz, Ph.D., for her exemplary leadership in serving as the NINR acting director since January 2020, in addition to her role as NIH associate deputy director in the NIH Office of the Director.”
As NINR director, Dr. Zenk will oversee NINR’s annual budget of nearly $170 million, the large majority of which supports extramural research at institutions across the Nation. NINR science seeks to improve the lives of individuals and families living with illness and to develop personalized strategies to maximize health and well-being at all stages of life, and across diverse populations and settings. NINR’s intramural program on the NIH campus conducts research to better understand and manage symptoms. Within both of those programs, NINR devotes significant resources to training and career development to foster the next generation of nurse scientists.
NIH researchers put complex, high-resolution data within reach for many more scientists
Scientists have developed new image processing techniques for microscopes that can reduce post-processing time up to several thousand-fold. The researchers are from the National Institutes of Health with collaborators at the University of Chicago and Zhejiang University, China.
In a paper published in Nature Biotechnology, Hari Shroff, Ph.D., chief of laboratory on High Resolution Optical Imaging at the National Institute of Biomedical Imaging and Bioengineering (NIBIB), describes new techniques that can significantly reduce the time needed to process the highly complex images that are created by the most cutting-edge microscopes. Such microscopes are often used to capture blood and brain cells moving through fish, visualize the neural development of worm embryos, and pinpoint individual organelles within entire organs.
As microscopes continue to get better, creating higher resolution images faster, researchers are finding they have more data than time to process it. While the videos themselves can be captured in minutes, the images could be terabytes in size and require weeks or, in some cases, months of processing time to be useable.
3D image of a mouse intestine with different antibodies in green, red, yellow, and purple.
Thousands of words, big and small, are crammed inside our memory banks just waiting to be swiftly withdrawn and strung into sentences. In a recent study of epilepsy patients and healthy volunteers, National Institutes of Health researchers found that our brains may withdraw some common words, like “pig,” “tank,” and “door,” much more often than others, including “cat,” “street,” and “stair.” By combining memory tests, brain wave recordings, and surveys of billions of words published in books, news articles and internet encyclopedia pages, the researchers not only showed how our brains may recall words but also memories of our past experiences.
“We found that some words are much more memorable than others. Our results support the idea that our memories are wired into neural networks and that our brains search for these memories, just the way search engines track down information on the internet,” said Weizhen (Zane) Xie, Ph.D., a cognitive psychologist and post-doctoral fellow at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS), who led the study published in Nature Human Behaviour. “We hope that these results can be used as a roadmap to evaluate the health of a person’s memory and brain.”
Dr. Xie and his colleagues first spotted these words when they re-analyzed the results of memory tests taken by 30 epilepsy patients who were part of a clinical trial led by Kareem Zaghloul, M.D., Ph.D., a neurosurgeon and senior investigator at NINDS. Dr. Zaghloul’s team tries to help patients whose seizures cannot be controlled by drugs, otherwise known as intractable epilepsy. During the observation period, patients spend several days at the NIH’s Clinical Center with surgically implanted electrodes designed to detect changes in brain activity.
NIH study suggests our brains may use search engine strategies to remember words and memories of our past experiences.
Genomic variants that cause common periodic fever have spread in Mediterranean populations over centuries, potentially protecting people from the plague
Researchers have discovered that Mediterranean populations may be more susceptible to an autoinflammatory disease because of evolutionary pressure to survive the bubonic plague. The study, carried out by scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, determined that specific genomic variants that cause a disease called familial Mediterranean fever (FMF) may also confer increased resilience to the plague.
The researchers suggest that because of this potential advantage, FMF-causing genomic variants have been positively selected for in Mediterranean populations over centuries. The findings were published in the journal Nature Immunology.
Over centuries, a biological arms race has been fought between humans and microbial pathogens. This evolutionary battle is between the human immune system and microorganisms trying to invade our bodies. Microbes affect the human genome in many ways. For example, they can influence some of the genomic variation that accumulates in human populations over time.
"In this era of a new pandemic, understanding the interplay between microbes and humans is ever critical," said Dr. Dan Kastner, NHGRI scientific director and a co-author on the paper. “We can witness evolution playing out before our very eyes.”
Specific genomic variants that cause a disease called familial Mediterranean fever (FMF) may also confer increased resilience to the plague. Image credit: Ernesto Del Aguila III, NHGRI
In a new study, a computer algorithm improved the accuracy and efficiency of cervical cancer screening compared with cytology (Pap test), the current standard for follow-up of women who test positive with primary human papillomavirus (HPV) screening. The new approach uses artificial intelligence (AI) to automate dual-stain evaluation and has clear implications for clinical care.
Findings from the study were published June 25, 2020, in the Journal of the National Cancer Institute. The algorithm was developed and the study conducted by investigators at the National Cancer Institute (NCI), part of the National Institutes of Health, in collaboration with researchers from several other institutions.
“We’re excited to show we have a fully automated approach to cervical cancer screening as a follow-up to a positive HPV test that outperformed the standard method in our study,” said Nicolas Wentzensen, M.D., Ph.D., of NCI’s Division of Cancer Epidemiology and Genetics, who led the study. “Based on our results, it could increase the efficiency of cervical cancer screening by finding more precancers and reducing false positives, which has the potential to eliminate a substantial number of unnecessary procedures among HPV-positive women.”
A slide from an automated dual-stain cytology test. The percentages are AI-generated likelihoods of positive results. The image at center (labeled 98.75%) shows a positive result.
National Institutes of Health investigators and colleagues have discovered that when the immune system first responds to infectious agents such as viruses or bacteria, a natural brake on the response prevents overactivation. Their new study in mBio describes this brake and the way pathogens such as SARS-CoV-2, the virus that causes COVID-19, turn it on. Their finding provides a potential target for an immunotherapy that might be applied to a wide range of infectious diseases.
When a cell senses an infectious agent with molecules called pathogen recognition receptors, part of its response is to increase cell surface expression of a molecule called CD47, otherwise known as the “don’t eat me” signal. Increased CD47 expression dampens the ability of cells called macrophages, the immune system’s first responders, to engulf infected cells and further stimulate the immune response. Upregulation of CD47 on cells was observed for diverse types of infections including those caused by mouse retroviruses, lymphocytic choriomeningitis virus, LaCrosse virus, SARS CoV-2, and by the bacteria Borrelia burgdorferi and Salmonella enterica typhi.
By blocking CD47-mediated signaling with antibodies in mice infected with lymphocytic choriomeningitis virus, the authors demonstrated they could enhance the speed of pathogen clearance. Furthermore, knocking out the CD47 gene in mice improved their ability to control M. tuberculosis infections and significantly prolonged their survival. In addition, retrospective studies of cells and plasma from people infected with hepatitis C virus indicated that humans also upregulate CD47. In these studies, inflammatory cytokine stimuli and direct infection both promoted increased CD47 expression.
Colorized scanning electron micrograph of a cell (purple) infected with SARS-COV-2 virus particles (yellow), isolated from a patient sample.
A team of researchers from the National Library of Medicine (NLM), part of the National Institutes of Health, identified genomic features of SARS-CoV-2, the virus that causes COVID-19, and other high-fatality coronaviruses that distinguish them from other members of the coronavirus family. This research could be a crucial step in helping scientists develop approaches to predict, by genome analysis alone, the severity of future coronavirus disease outbreaks and detect animal coronaviruses that have the potential to infect humans. The findings were published this week in the Proceedings of the National Academy of Sciences.
COVID-19, an unprecedented public health emergency, has now claimed more than 380,000 lives worldwide. This crisis prompts an urgent need to understand the evolutionary history and genomic features that contribute to the rampant spread of SARS-CoV-2.
“In this work, we set out to identify genomic features unique to those coronaviruses that cause severe disease in humans,” said Dr. Eugene Koonin, an NIH Distinguished Investigator in the intramural research program of NLM’s National Center for Biotechnology Information, and the lead author of the study. “We were able to identify several features that are not found in less virulent coronaviruses and that could be relevant for pathogenicity in humans. The actual demonstration of the relevance of these findings will come from direct experiments that are currently getting under way.”
The full genomes of all human coronaviruses were aligned to identify regions (red) that might code for lethal differences in the virus that causes COVID-19 as well as SARS and MERS. These differences could be targets for testing or treatments.
