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.
Results will inform development of long-acting antibody-based HIV prevention tools
An investigational anti-HIV antibody delivered intravenously once every eight weeks safely and effectively prevented acquisition of HIV strains sensitive to that antibody, but did not significantly reduce overall HIV acquisition after 80 weeks among participants in two multinational clinical trials. Known as the Antibody-Mediated Prevention (AMP) Studies, the Phase 2b trials are sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The studies are being conducted jointly by the HIV Vaccine Trials Network (HVTN) and HIV Prevention Trials Network (HPTN).
While currently available HIV treatment and prevention tools have greatly reduced transmission of the virus, there remains a need for long-acting HIV prevention strategies that are acceptable and desirable to people from diverse communities worldwide. Broadly neutralizing antibodies (bNAbs), which arise naturally in some people living with HIV and can stop a wide range of HIV strains from infecting human cells in the laboratory, are considered promising candidates for long-acting HIV prevention. These antibodies could be given directly by either infusion or injection or could be elicited by an HIV vaccine.
Launched in 2016, the AMP Studies aimed to establish whether infusions of a bNAb called VRC01 are safe, tolerable and effective at preventing HIV acquisition. The NIAID Vaccine Research Center (VRC) discovered VRC01 in 2010 in the blood of a person living with HIV and subsequently manufactured the antibody for the AMP Studies. The two trials included more than 4,600 participants. Men and transgender people who have sex with men were enrolled in the Americas and Europe — geographic regions where HIV subtype B predominates. Women were enrolled in sub-Saharan Africa, where HIV subtype C is dominant. Results will be discussed at a press conference and oral presentation during the 4th HIV Research for Prevention Conference.
Scanning electromicrograph of an HIV-infected T cell.
Contrary to previous findings, low-dose aspirin therapy before conception and during early pregnancy may increase pregnancy chances and live births among women who have experienced one or two prior miscarriages, suggests a study by researchers at the National Institutes of Health. Rather than looking solely at the difference in pregnancy rates between women who were given aspirin and those receiving a placebo, the study also accounted for differences in total aspirin use between women who deviated from the daily regimen and those who adhered to it.
Published in 2014, the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial included more than 1,000 women between 18 and 40 years old with one or two previous miscarriages. The women received either daily low-dose aspirin (81 milligrams) or a placebo while trying to conceive. If they did conceive, they would continue to receive this regimen through the 36th week of pregnancy. Although the study found no overall difference in pregnancy loss rates between the two groups, there was a higher birthrate for the subgroup of women who had experienced only one previous miscarriage before the 20th week of pregnancy.
Unlike the original analysis, the current reanalysis considered whether a participant adhered to the treatment or skipped days or discontinued it entirely for side effects such as bleeding, nausea or vomiting. Compared to the placebo group, for every 100 women, adhering to the aspirin regimen for five to seven days a week led to eight more positive pregnancy tests, six fewer pregnancy losses, and culminated in 15 more live births. Women who adhered to the therapy four days per week experienced similar results. The researchers concluded that taking low-dose aspirin at least four days per week could improve the odds for pregnancy and live birth in this group of women.
Analysis of patients with rare condition uncovers key pathway for human development
Researchers at the National Institutes of Health have discovered a new genetic disorder characterized by developmental delays and malformations of the brain, heart and facial features. Named linkage-specific-deubiquitylation-deficiency-induced embryonic defects syndrome (LINKED), it is caused by a mutated version of the OTUD5 gene, which interferes with key molecular steps in embryo development. The findings indicate that the newly identified pathway may be essential for human development and may also underlie other disorders that are present at birth. The information will help scientists better understand such diseases — both common and rare — and improve patient care. The results were reported Jan. 20, 2021 in Science Advances.
“Our discovery of the dysregulated neurodevelopmental pathway that underlies LINKED syndrome was only possible through the teamwork of geneticists, developmental biologists and biochemists from NIH,” said Achim Werner, Ph.D., an investigator at the National Institute of Dental and Craniofacial Research (NIDCR) and lead author. “This collaboration provided the opportunity to pinpoint the likely genetic cause of disease, and then take it a step further to precisely define the sequence of cellular events that are disrupted to cause the disease.”
The project began when David B. Beck, M.D., Ph.D., a clinical fellow in the laboratory of Dan Kastner M.D., Ph.D., at the National Human Genome Research Institute (NHGRI) and co-first author, was asked to consult on a male infant who had been born with severe birth defects that included abnormalities of the brain, craniofacial skeleton, heart and urinary tract. An in-depth examination of siblings’ and family members’ genomes, combined with genetic bioinformatics analyses, revealed a mutation in the OTUD5 gene as the likely cause of the condition. Through outreach to other researchers working on similar problems, Beck found seven additional males ranging from 1 to 14 years of age who shared symptoms with the first patient and had varying mutations in the OTUD5 gene.
Compared to a disease-free mother (left), differentiated LINKED patient cells (right) lack markers of normal development of the brain, spinal cord and craniofacial skeleton (pink, green and yellow). Image credit: Werner lab, NIDCR
People on a low-fat, plant-based diet ate fewer daily calories but had higher insulin and blood glucose levels, compared to when they ate a low-carbohydrate, animal-based diet, according to a small but highly controlled study at the National Institutes of Health. Led by researchers at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the study compared the effects of the two diets on calorie intake, hormone levels, body weight, and more. The findings, published in Nature Medicine, broaden understanding of how restricting dietary carbohydrates or fats may impact health.
“High-fat foods have been thought to result in excess calorie intake because they have many calories per bite. Alternatively, high-carb foods can cause large swings in blood glucose and insulin that may increase hunger and lead to overeating,” said NIDDK Senior Investigator Kevin Hall, Ph.D., the study’s lead author. “Our study was designed to determine whether high-carb or high-fat diets result in greater calorie intake.”
The researchers housed 20 adults without diabetes for four continuous weeks in the NIH Clinical Center’s Metabolic Clinical Research Unit. The participants, 11 men and nine women, received either a plant-based, low-fat diet or an animal-based, low-carbohydrate diet for two weeks, immediately followed by two weeks on the alternate diet. The low-fat diet was high in carbohydrates. The low-carbohydrate diet was high in fats. Both diets were minimally processed and had equivalent amounts of non-starchy vegetables. The participants were given three meals a day, plus snacks, and could eat as much as desired.
Examples of dinners given to study participants: low-carb, animal-based diet (left) and low-fat, plant-based diet (right). Image credit: Amber Courville and Paule Joseph
NIH study finds biggest increase among American Indians and Alaska Natives
Methamphetamine overdose deaths surged in an eight-year period in the United States, according to a study that will published today in JAMA Psychiatry. The analysis revealed rapid rises across all racial and ethnic groups, but American Indians and Alaska Natives had the highest death rates overall. The research was conducted at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.
Deaths involving methamphetamines more than quadrupled among non-Hispanic American Indians and Alaska Natives from 2011-2018 (from 4.5 to 20.9 per 100,000 people) overall, with sharp increases for both men (from 5.6 to 26.4 per 100,000 from 2011-2018) and women (from 3.6 to 15.6 per 100,000 from 2012-2018) in that group. The findings highlight the urgent need to develop culturally tailored, gender-specific prevention and treatment strategies for methamphetamine use disorder to meet the unique needs of those who are most vulnerable to the growing overdose crisis. Long-term decreased access to education, high rates of poverty and discrimination in the delivery of health services are among factors thought to contribute to health disparities for American Indians and Alaska Natives.
“While much attention is focused on the opioid crisis, a methamphetamine crisis has been quietly, but actively, gaining steam—particularly among American Indians and Alaska Natives, who are disproportionately affected by a number of health conditions,” said Nora D. Volkow, M.D., NIDA director and a senior author of the study. “American Indian and Alaska Native populations experience structural disadvantages but have cultural strengths that can be leveraged to prevent methamphetamine use and improve health outcomes for those living with addiction.”
Non-Hispanic American Indians and Alaska Natives: Overdose deaths involving methamphetamine rose from 4.5 to 20.9 per 100,000 people ages 25 to 54 during 2011-2018.
NIH study shows specific set of immune cells can harm and also help brain after injury
Researchers from the National Institutes of Health have discovered Jekyll and Hyde immune cells in the brain that ultimately help with brain repair but early after injury can lead to fatal swelling, suggesting that timing may be critical when administering treatment. These dual-purpose cells, which are called myelomonocytic cells and which are carried to the brain by the blood, are just one type of brain immune cell that NIH researchers tracked, watching in real-time as the brain repaired itself after injury. The study, published in Nature Neuroscience, was supported by the National Institute of Neurological Disorders and Stroke (NINDS) Intramural Research Program at NIH.
“Fixing the brain after injury is a highly orchestrated, coordinated process, and giving a treatment at the wrong time could end up doing more harm than good,” said Dorian McGavern, Ph.D., NINDS scientist and senior author of the study.
Cerebrovascular injury, or damage to brain blood vessels, can occur following several conditions including traumatic brain injury or stroke. Dr. McGavern, along with Larry Latour, M.D., NINDS scientist, and their colleagues, observed that a subset of stroke patients developed bleeding and swelling in the brain after surgical removal of the blood vessel clot responsible for the stroke. The swelling, also known as edema, results in poor outcomes and can even be fatal as brain structures become compressed and further damaged.
NIH researchers tracked the progression of brain blood vessel repair after injury. At day 1 after injury (left panel), the brain had areas of bleeding and broken vessels. Ten days later (right panel) the vessels were almost completely rebuilt.
Taurine, which helps the body digest fats and oils, could offer treatment benefit
Scientists studying the body’s natural defenses against bacterial infection have identified a nutrient — taurine — that helps the gut recall prior infections and kill invading bacteria, such as Klebsiella pneumoniae (Kpn). The finding, published in the journal Cell by scientists from five institutes of the National Institutes of Health, could aid efforts seeking alternatives to antibiotics.
Scientists know that microbiota — the trillions of beneficial microbes living harmoniously inside our gut — can protect people from bacterial infections, but little is known about how they provide protection. Scientists are studying the microbiota with an eye to finding or enhancing natural treatments to replace antibiotics, which harm microbiota and become less effective as bacteria develop drug resistance.
The scientists observed that microbiota that had experienced prior infection and transferred to germ-free mice helped prevent infection with Kpn. They identified a class of bacteria — Deltaproteobacteria — involved in fighting these infections, and further analysis led them to identify taurine as the trigger for Deltaproteobacteria activity.
Colorized scanning electron micrograph showing carbapenem-resistant Klebsiella pneumoniae interacting with a human neutrophil.
DNA-based “liquid biopsy” could help save lives and reduce health disparities
Researchers have developed a blood test that could make it possible for doctors to detect — then quickly prevent or slow down — acute heart transplant rejection, a potentially deadly condition that occurs in the early months after a patient has received a donor heart. They estimate that the test could eliminate up to 80 percent of invasive heart tissue biopsies currently used to detect rejection.
In studies of a group of nearly 200 heart transplant recipients, the new blood test performed better than tissue biopsies, as it signaled problems even when no outward signs of rejection were evident.
The study was primarily funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. The study’s findings are scheduled to appear January 13 in Circulation, a publication of the American Heart Association.
“There’s an urgent need for an alternative method to monitor patients for acute heart transplant rejection,” said Sean Agbor-Enoh, M.D., Ph.D., study co-author and chief of the NHLBI’s Laboratory of Applied Precision Omics.
Illustration shows DNA fragments (yellow) derived from a transplanted heart alongside the patient’s own DNA (blue). A new blood test measures donor DNA fragments and detects acute heart transplant rejection earlier than current methods. Image credit: Erina He, NIH Medical Arts
Salmonella enterica serovar Typhimurium bacteria (S. Typhimurium) commonly cause human gastroenteritis, inflammation of the lining of the intestines. The bacteria live inside the gut and can infect the epithelial cells that line its surface. Many studies have shown that Salmonella use a “run-and-tumble” method of short swimming periods (runs) punctuated by tumbles when they randomly change direction, but how they move within the gut is not well understood.
National Institutes of Health scientists and their colleagues believe they have identified a S. Typhimurium protein, McpC (Methyl-accepting chemotaxis protein C), that allows the bacteria to swim straight when they are ready to infect cells. This new study, published in Nature Communications, describes S. Typhimurium movement and shows that McpC is required for the bacteria to invade surface epithelial cells in the gut.
The study authors suggest that McpC is a potential target for developing new antibacterial treatments to hinder the ability of S. Typhimurium to infect intestinal epithelial cells and colonize the gut. National Institute of Allergy and Infectious Diseases scientists at Rocky Mountain Laboratories in Hamilton, Montana, led the study. Collaborators included groups from the University of Texas A&M campuses in College Station and Kingsville.
Salmonella bacteria (pink), a common cause of foodborne disease, invade a human epithelial cell (yellow).
Women who use marijuana could have a more difficult time conceiving a child than women who do not use marijuana, suggests a study by researchers at the National Institutes of Health. Marijuana use among the women’s partners — which could have influenced conception rates — was not studied. The researchers were led by Sunni L. Mumford, Ph.D., of the Epidemiology Branch in NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development. The study appears in Human Reproduction.
The women were part of a larger group trying to conceive after one or two prior miscarriages. Women who said they used cannabis products — marijuana or hashish — in the weeks before pregnancy, or who had positive urine tests for cannabis use, were around 40 percent less likely to conceive per monthly cycle than women who did not use cannabis. The authors noted that although the findings suggest cannabis could affect women’s fertility, they should be tempered with caution as the study observed a relatively small number of cannabis users. However, the authors say their results suggest that women trying to conceive should exercise caution with cannabis use until more definitive evidence is available.
The researchers analyzed data from a broader study of more than 1,200 women ages 18 to 40 with one or two pregnancy losses. The women participated in the study for up to six monthly cycles while attempting pregnancy and throughout pregnancy if conception occurred. After enrolling in the study, the women responded to a questionnaire asking if they had used marijuana, pot, or hashish in the past 12 months, with responses ranging from never, rarely, occasionally, sometimes, often, to daily. Each woman also provided urine samples for analysis when they first entered the study and after six months if they did not conceive or at the time of positive pregnancy test if they conceived.
