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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:

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Here’s when your weight loss will plateau, according to science

CNN
Monday, April 22, 2024

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 to drop 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 scientists use human cerebral organoid to test drug for deadly brain disease

Approximately two years after establishing a human cerebral organoid system to study Creutzfeldt-Jakob disease (CJD), National Institutes of Health researchers have further developed the model to screen drugs for potential CJD treatment. The scientists, from NIH’s National Institute of Allergy and Infectious Diseases (NIAID), describe their work in Scientific Reports.

Human cerebral organoids are small balls of human brain cells ranging in size from a poppy seed to a pea; scientists use human skin cells to create them. CJD, a fatal neurodegenerative brain disease of humans caused by infectious prion proteins, affects about 1 in 1 million people each year. It can arise spontaneously, result from a hereditary mutation within the prion gene, or arise due to infection, for example, from eating contaminated meat products. A notable example of this occurred in the United Kingdom in the mid-1990s following an outbreak of bovine spongiform encephalopathy in cattle. There are no preventive or therapeutic treatments for CJD.

The lack of a completely human CJD model has been a considerable barrier hindering the discovery of potential therapies. Studies in mice have failed to identify treatments that were then effective when tried in patients. The human cerebral organoid CJD model holds promise that this barrier can be eliminated. Cerebral organoids have organization, structure, and electrical signaling systems similar to human brain tissue. Because they can survive in a controlled environment for months to years, cerebral organoids also are ideal for studying nervous system diseases over lengthy periods of time. Cerebral organoids have been used as models to study Zika virus infection, Alzheimer’s disease, and Down syndrome.

A cerebral organoid shown overlaid with test results from prion infected organoids that were left untreated or treated with PPS

A cerebral organoid shown overlaid with test results from prion infected organoids that were left untreated or treated with PPS. The results show that treatment reduces disease-associated protein.

IRP scientists discover how DNA fragments can trigger inflammation in sickle cell disease

Researchers have discovered that DNA from the mitochondria — the cell’s “powerhouses” — acts as a danger signal in the body and triggers inflammation in people with sickle cell disease. A better understanding of mitochondrial DNA, long known to circulate in human blood, may provide vital insight into how to stop the underlying chronic inflammation that marks this inherited red blood cell disorder. It could also lead to new ways to reduce the pain crises suffered by people living with the life-threatening disease.

The study, published in the journal Blood, was supported by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.

“These study findings suggest that measuring DNA of mitochondrial origin could help us better understand its role in pain crises, destruction of red blood cells, and other inflammatory events in sickle cell disease,” said Swee Lay Thein, M.B., D.Sc., chief of the Sickle Cell Branch at NHLBI. “It could also serve as a marker of disease progression and a way to measure the effectiveness of therapeutic interventions.”

Scanning electron microscopy image of mitochondrial bundles in several sickle cell red blood cells, showing evidence that circulating red blood cells from people with sickle cell disease abnormally retain mitochondria

Scanning electron microscopy image of mitochondrial bundles in several sickle cell red blood cells, showing evidence that circulating red blood cells from people with sickle cell disease abnormally retain mitochondria.

NIH halts trial of COVID-19 convalescent plasma in emergency department patients with mild symptoms

Study shows the treatment is safe, but provides no significant benefit in this group

The National Institutes of Health has halted a clinical trial evaluating the safety and effectiveness of COVID-19 convalescent plasma in treating emergency department patients who developed mild to moderate symptoms of COVID-19, the disease caused by the coronavirus SARS-CoV-2.

An independent data and safety monitoring board (DSMB) met on Feb. 25, 2021 for the second planned interim analysis of the trial data and determined that while the convalescent plasma intervention caused no harm, it was unlikely to benefit this group of patients. After the meeting, the DSMB recommended that the National Heart, Lung, and Blood Institute (NHLBI), part of NIH, stop enrolling new patients into the study. NHLBI did so immediately.

Launched in August 2020, the Clinical Trial of COVID-19 Convalescent Plasma of Outpatients (C3PO) was being conducted at 47 hospital emergency departments across the United States and had enrolled 511 of the 900 participant recruitment goal. It was specifically looking at the effectiveness of COVID-19 convalescent plasma – blood plasma derived from patients who have recovered from COVID-19 – in adults who came to an emergency department with mild to moderate symptoms they had for a week or less. These patients also had at least one risk factor associated with severe COVID-19, such as obesity, hypertension, diabetes, heart disease, or chronic lung disease, but none were ill enough at the time to be hospitalized.

Colorized scanning electron micrograph of a cell (pink) infected with SARS-CoV-2 virus particles (teal)

Colorized scanning electron micrograph of a cell (pink) infected with SARS-CoV-2 virus particles (teal), isolated from a patient sample.

IRP study finds that people with SARS-CoV-2 antibodies may have a low risk of future infection

People who have had evidence of a prior infection with SARS-CoV-2, the virus that causes COVID-19, appear to be well protected against being reinfected with the virus, at least for a few months, according to a newly published study from the National Cancer Institute (NCI). This finding may explain why reinfection appears to be relatively rare, and it could have important public health implications, including decisions about returning to physical workplaces, school attendance, the prioritization of vaccine distribution, and other activities.

For the study, researchers at NCI, part of the National Institutes of Health, collaborated with two health care data analytics companies (HealthVerity and Aetion, Inc.) and five commercial laboratories. The findings were published on Feb. 24 in JAMA Internal Medicine.

“While cancer research and cancer care remain the primary focus of NCI’s work, we were eager to lend our expertise in serological sciences to help address the global COVID-19 pandemic, at the request of Congress,” said NCI Director Norman E. “Ned” Sharpless, M.D., who was one of the coauthors on the study. “We hope that these results, in combination with those of other studies, will inform future public health efforts and help in setting policy.”

“The data from this study suggest that people who have a positive result from a commercial antibody test appear to have substantial immunity to SARS-CoV-2, which means they may be at lower risk for future infection,” said Lynne Penberthy, M.D., M.P.H., associate director of NCI’s Surveillance Research Program, who led the study. “Additional research is needed to understand how long this protection lasts, who may have limited protection, and how patient characteristics, such as comorbid conditions, may impact protection. We are nevertheless encouraged by this early finding.”

A single elongated CCL-81 cell heavily infected with SARS-CoV-2 virus particles.

A single elongated CCL-81 cell heavily infected with SARS-CoV-2 virus particles. The small spherical structures in the image are SARS-CoV-2 virus particles. The string-like protrusions from the cells are cell projections or pseudopodium. Image captured at the NIAID Integrated Research Facility (IRF) in Fort Detrick, Maryland.

New experiences enhance learning by resetting key brain circuit

A study of spatial learning in mice shows that exposure to new experiences dampens established representations in the brain’s hippocampus and prefrontal cortex, allowing the mice to learn new navigation strategies. The study, published in Nature, was supported by the National Institutes of Health.

“The ability to flexibly learn in new situations makes it possible to adapt to an ever-changing world,” noted Joshua A. Gordon, M.D., Ph.D., a senior author on the study and director of the National Institute of Mental Health, part of NIH. “Understanding the neural basis of this flexible learning in animals gives us insight into how this type of learning may become disrupted in humans.”

Dr. Gordon co-supervised the research project with Joseph A. Gogos, M.D., Ph.D., and Alexander Z. Harris, M.D., Ph.D., both of Columbia University, New York City.

Whenever we encounter new information, that information must be consolidated into a stable, lasting memory for us to recall it later. A key mechanism in this memory consolidation process is long-term potentiation, which is a persistent strengthening of neural connections based on recent patterns of activity. Although this strengthening of neural connections may be persistent, it can’t be permanent, or we wouldn’t be able to update memory representations to accommodate new information. In other words, our ability to remember new experiences and learn from them depends on information encoding that is both enduring and flexible.

Mouse study shows bacteriophage therapy could fight drug-resistant Klebsiella pneumoniae

Using viruses instead of antibiotics to tame troublesome drug-resistant bacteria is a promising strategy, known as bacteriophage or “phage therapy.” Scientists at the National Institutes of Health have used two different bacteriophage viruses individually and then together to successfully treat research mice infected with multidrug-resistant Klebsiella pneumoniae sequence type 258 (ST258). The bacterium K. pneumoniae ST258 is included on a Centers for Disease Control and Prevention list of biggest antibiotic resistance threats in the United States. High rates of morbidity and mortality are associated with untreated K. pneumoniae infections.

Phage therapy has been pursued for about a century, though conclusive research studies are rare and clinical results — from a handful of reports — have provided mixed results. In the new paper published in the journal mBio, the NIH scientists note that phages are of great interest today because of a dearth of alternative treatment options for drug-resistant infections. Bacterial resistance has emerged against even the newest drug combinations, leaving some patients with few or no effective treatment options.

In research conducted in Hamilton, Montana, at Rocky Mountain Laboratories — part of the NIH’s National Institute of Allergy and Infectious Diseases — and in collaboration with the National Cancer Institute in Bethesda, Maryland, scientists completed a series of studies on research mice infected with ST258. They treated the mice with either phage P1, phage P2, or a combination of the two, all injected at different times following ST258 infection. The scientists had isolated phages P1 and P2 in 2017 from raw sewage that they screened for viruses that would infect ST258 — an indication that phages can be found just about any place. Phages P1 and P2 are viruses from the order Caudovirales, which naturally infect bacteria.

Colorized scanning electron micrograph showing carbapenem-resistant Klebsiella pneumoniae interacting with a human neutrophil

Colorized scanning electron micrograph showing carbapenem-resistant Klebsiella pneumoniae interacting with a human neutrophil.

Genetic study of Lewy body dementia supports ties to Alzheimer’s and Parkinson’s diseases

NIH-led study locates five genes that may play a critical role in Lewy body dementia

In a study led by National Institutes of Health researchers, scientists found that five genes may play a critical role in determining whether a person will suffer from Lewy body dementia, a devastating disorder that riddles the brain with clumps of abnormal protein deposits called Lewy bodies. Lewy bodies are also a hallmark of Parkinson’s disease. The results, published in Nature Genetics, not only supported the disease’s ties to Parkinson’s disease but also suggested that people who have Lewy body dementia may share similar genetic profiles to those who have Alzheimer’s disease.

“Lewy body dementia is a devastating brain disorder for which we have no effective treatments. Patients often appear to suffer the worst of both Alzheimer’s and Parkinson’s diseases. Our results support the idea that this may be because Lewy body dementia is caused by a spectrum of problems that can be seen in both disorders,” said Sonja Scholz, M.D., Ph.D., investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We hope that these results will act as a blueprint for understanding the disease and developing new treatments.”

The study was led by Dr. Scholz’s team and researchers in the lab of Bryan J. Traynor, M.D., Ph.D., senior investigator at the NIH’s National Institute on Aging (NIA).

diagram showing connections between Lewy body dementia and Alzheimer's and Parkinson's disease

Researchers propose that humidity from masks may lessen severity of COVID-19

NIH study compares how different face masks affect humidity inside the mask

Masks help protect the people wearing them from getting or spreading SARS-CoV-2, the virus that causes COVID-19, but now researchers from the National Institutes of Health have added evidence for yet another potential benefit for wearers: The humidity created inside the mask may help combat respiratory diseases such as COVID-19.

The study, led by researchers in the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), found that face masks substantially increase the humidity in the air that the mask-wearer breathes in. This higher level of humidity in inhaled air, the researchers suggest, could help explain why wearing masks has been linked to lower disease severity in people infected with SARS-CoV-2, because hydration of the respiratory tract is known to benefit the immune system. The study published in the Biophysical Journal.

“We found that face masks strongly increase the humidity in inhaled air and propose that the resulting hydration of the respiratory tract could be responsible for the documented finding that links lower COVID-19 disease severity to wearing a mask,” said the study’s lead author, Adriaan Bax, Ph.D., NIH Distinguished Investigator. “High levels of humidity have been shown to mitigate severity of the flu, and it may be applicable to severity of COVID-19 through a similar mechanism.”

NIDDK’s Dr. Joseph Courtney breathes into sealed box while wearing a mask

NIDDK’s Dr. Joseph Courtney breathes into sealed box while wearing a mask.

Study identifies risk factors for elevated anxiety in young adults during COVID-19 pandemic

Findings on impact of childhood temperament could help with anxiety prevention efforts

A new study has identified early risk factors that predicted heightened anxiety in young adults during the coronavirus (COVID-19) pandemic. The findings from the study, supported by the National Institutes of Health and published in the Journal of the American Academy of Child and Adolescent Psychiatry, could help predict who is at greatest risk of developing anxiety during stressful life events in early adulthood and inform prevention and intervention efforts.

The investigators examined data from 291 participants who had been followed from toddlerhood to young adulthood as part of a larger study on temperament and socioemotional development. The researchers found that participants who continued to show a temperament characteristic called behavioral inhibition in childhood were more likely to experience worry dysregulation in adolescence (age 15), which in turn predicted elevated anxiety during the early months of the COVID-19 pandemic when the participants were in young adulthood (around age 18).

“People differ greatly in how they handle stress,” said Daniel Pine, M.D., a study author and chief of the National Institute of Mental Health (NIMH) Section on Development and Affective Neuroscience. “This study shows that children’s level of fearfulness predicts how much stress they experience later in life when they confront difficult circumstances, such as the pandemic.”

Distinctness of mental disorders traced to differences in gene readouts

NIH researchers take “deep dive” into brain’s transcriptome

A new study suggests that differences in the expression of gene transcripts — readouts copied from DNA that help maintain and build our cells — may hold the key to understanding how mental disorders with shared genetic risk factors result in different patterns of onset, symptoms, course of illness, and treatment responses. Findings from the study, conducted by researchers at the National Institute of Mental Health (NIMH), part of the National Institutes of Health, appear in the journal Neuropsychopharmacology.

“Major mental disorders, such as schizophrenia, bipolar disorder, and major depressive disorder, share common genetic roots, but each disorder presents differently in each individual,” said Francis J. McMahon, M.D., a senior author of the study and chief of the Human Genetics Branch, part of the Intramural Research Program NIMH. “We wanted to investigate why disorders present differently, despite this seeming genetic similarity.”

McMahon and colleagues suspected that the brain’s transcriptome may hold some clues. The human genome is made up of DNA that contains instructions for helping maintain and build our cells. These instructions must be read and then copied into so-called “transcripts” for them to be carried out. Importantly, many different transcripts can be copied from a single gene, yielding a variety of proteins and other outputs. The transcriptome is the full set of transcripts found within the body.

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This page was last updated on Monday, April 22, 2024