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:
The act of cooking offers the chance to unwind and create something special, whether you’re planning to feed a crowd or just yourself. And while you may have noticed feeling good after whipping up that perfect pie or braise, there’s actually a lot of scientific data to suggest that cooking can have a positive impact on mental health.
One meta-analysis (a report of pre-existing research) from the National Institutes of Health looked at 11 studies and found that “cooking interventions” — encouraging people to follow certain recipes or giving people cooking classes — can improve a person’s mental well-being. It specifically found that people who participated in cooking interventions reported having better self-esteem and quality of life, as well as a more positive emotional state after the fact. Another study even discovered that baking can help raise a person’s confidence level.
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.
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.”
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.
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.”
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.
For patients with cancers that do not respond to immunotherapy drugs, adjusting the composition of microorganisms in the intestines — known as the gut microbiome — through the use of stool, or fecal, transplants may help some of these individuals respond to the immunotherapy drugs, a new study suggests. Researchers at the National Cancer Institute (NCI) Center for Cancer Research, part of the National Institutes of Health, conducted the study in collaboration with investigators from UPMC Hillman Cancer Center at the University of Pittsburgh.
In the study, some patients with advanced melanoma who initially did not respond to treatment with an immune checkpoint inhibitor, a type of immunotherapy, did respond to the drug after receiving a transplant of fecal microbiota from a patient who had responded to the drug. The results suggest that introducing certain fecal microorganisms into a patient’s colon may help the patient respond to drugs that enhance the immune system’s ability to recognize and kill tumor cells. The findings appeared in Science on February 4, 2021.
“In recent years, immunotherapy drugs called PD-1 and PD-L1 inhibitors have benefited many patients with certain types of cancer, but we need new strategies to help patients whose cancers do not respond,” said study co-leader Giorgio Trinchieri, M.D., chief of the Laboratory of Integrative Cancer Immunology in NCI’s Center for Cancer Research. “Our study is one of the first to demonstrate in patients that altering the composition of the gut microbiome can improve the response to immunotherapy. The data provide proof of concept that the gut microbiome can be a therapeutic target in cancer.”
An experimental single-dose, intranasal influenza vaccine was safe and produced a durable immune response when tested in a Phase 1 study published in the Journal of Clinical Investigation. The investigational vaccine, called Ad4-H5-VTN, is a recombinant, replicating adenovirus vaccine designed to spur antibodies to hemagglutinin, a protein found on the surface of influenza viruses that attaches to human cells.
The investigational vaccine was developed by Emergent Biosolutions Inc., (Gaithersburg, Maryland). It was administered intranasally (28 study participants), as an oral capsule (10 participants) and via a tonsillar swab (25 participants) to healthy men and non-pregnant women ages 18 to 49 years.
The participants who received the vaccine intranasally or via tonsillar swab showed significantly higher H5-specific neutralizing antibody levels compared to the group receiving the vaccine capsule orally. The participants who received the intranasal vaccine shed viral DNA for two-to-four weeks, but virus could be cultured for a median of only one day. Participants had evidence of H5-specific CD4+ and CD8+ T-cell responses. Additionally, volunteers who received the intranasal vaccine had high levels of serum neutralizing antibodies at 26 weeks after vaccination, and this level was unchanged at three to five years after a single intranasal dose of the vaccine. The duration of viral shedding correlated with a high magnitude of neutralizing antibody response at week 26. In addition, the intranasal vaccine induced a mucosal antibody response in the nose, mouth, and rectum.
3D print of influenza virus. The virus surface (yellow) is covered with proteins called hemagglutinin (blue) and neuraminidase (red) that enable the virus to enter and infect human cells.
Researchers at the National Institutes of Health and their collaborators found that inhaling unfragmented hyaluronan improves lung function in patients suffering from severe exacerbation of chronic obstructive pulmonary disease (COPD). Hyaluronan, a sugar secreted by living tissue that acts as a scaffold for cells, is also used in cosmetics as a skin moisturizer and as a nasal spray to moisturize lung airways. Utilized as a treatment, hyaluronan shortened the amount of time COPD patients in intensive care needed breathing support, decreased their number of days in the hospital, and saved money by reducing their hospital stay.
The study, published online in Respiratory Research, is a good example of how examining the impacts of environmental pollution on the lungs can lead to viable treatments. Several years ago, co-senior author Stavros Garantziotis, M.D., medical director of the Clinical Research Unit at the National Institute of Environmental Health Sciences (NIEHS), part of NIH, showed that exposure to pollution causes hyaluronan in the lungs to break down into smaller fragments. These fragments irritate lung tissue and activate the immune system, leading to constriction and inflammation of the airways. He determined that inhalation of healthy, unfragmented hyaluronan reduces inflammation by outcompeting the smaller hyaluronan fragments.
Garantziotis offered an analogy for how the inflammation occurs. He said hyaluronan surrounds cells like mortar surrounds bricks. Introducing pollution causes cracks in the mortar, breaking it into smaller chunks.
"These smaller chunks irritate the body and activate the immune system, leading to inflammation," Garantziotis said. "Reintroducing the full-length hyaluronan, like a fresh coat of mortar, means it is less irritating and reduces the amount of inflammation."
Research shows that inhaling hyaluronan interferes at almost every step of the COPD cycle, making it a potent treatment for chronic lung disease.
Findings indicate cones precede rods as targets for infection
The earliest eye damage from prion disease takes place in the cone photoreceptor cells, specifically in the cilia and the ribbon synapses, according to a new study of prion protein accumulation in the eye by National Institutes of Health scientists. Prion diseases originate when normally harmless prion protein molecules become abnormal and gather in clusters and filaments in the human body and brain.
Understanding how prion diseases develop, particularly in the eye because of its diagnostic accessibility to clinicians, can help scientists identify ways to slow the spread of prion diseases. The scientists say their findings, published in the journal Acta Neuropathologica Communications, may help inform research on human retinitis pigmentosa, an inherited disease with similar photoreceptor degeneration leading to blindness.
Prion diseases are slow, degenerative and usually fatal diseases of the central nervous system that occur in people and some other mammals. Prion diseases primarily involve the brain, but also can affect the eyes and other organs. Within the eye, the main cells infected by prions are the light-detecting photoreceptors known as cones and rods, both located in the retina.
(left panel) Early in prion infection, a prion protein aggregate (magenta) blocks the entrance to a cilium (green) in a retinal photoreceptor. (lower right) In prion-infected retina, prion protein (magenta) accumulates under the horseshoe-shaped ribbon synapses (green) found in photoreceptor terminals.
Approach could provide new path for difficult-to-treat forms of Leber congenital amaurosis
Scientists at the National Eye Institute (NEI) have developed a promising gene therapy strategy for a rare disease that causes severe vision loss in childhood. A form of Leber congenital amaurosis, the disease is caused by autosomal-dominant mutations in the CRX gene, which are challenging to treat with gene therapy. The scientists tested their approach using lab-made retinal tissues built from patient cells, called retinal organoids. This approach, which involved adding copies of the normal gene under its native control mechanism, partially restored CRX function. The study report appears today in Stem Cell Reports. NEI is part of the National Institutes of Health.
“Our treatment approach, which adds more copies of the normal gene, could potentially treat autosomal-dominant LCA caused by a variety of mutations,” said Anand Swaroop, Ph.D., chief of the NEI Neurobiology, Neurodegeneration and Repair Laboratory and senior author of the report.
The U.S. Food and Drug Administration approved Luxturna in 2017 for the treatment of LCA patients with mutations in a gene called RPE65. Although hailed as a major advance in gene therapy, Luxturna is ineffective against other forms of LCA, including those caused by autosomal-dominant mutations in CRX.
Fluorescently labeled organoid showing columnal cells in outer ring.
