Scientists have been searching for the optimal coronavirus vaccine since the Covid-19 pandemic started. The mRNA vaccines developed through the federal government’s “Operation Warp Speed” program were a massive innovation; however, annually updating those boosters for specific SARS-CoV-2 variants is inefficient for scientists and patients. SARS-CoV-2 is just one member of the Sarbecovirus (SARS Betacoronavirus) subfamily (others include SARS-CoV-1, which caused the 2002 SARS outbreak, as well as other viruses circulating in bats that could cause future pandemics).
Researchers at the Georgia Institute of Technology and the University of Wisconsin-Madison have developed a new vaccine that offers broad protection against not only SARS-CoV-2 variants, but also other bat sarbecoviruses. The groundbreaking trivalent vaccine has shown complete protection with no trace of virus in the lungs, marking a significant step toward a universal vaccine for coronaviruses.
“We had been working on strategies to make a broadly protective vaccine for a while,” said Ravi Kane, professor in the School of Chemical and Biomolecular Engineering. “This vaccine may protect not just against the current strain circulating that year, but also future variants.”
They presented their findings in “Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine,” published in the February edition of Nature Communications.
Kane and his research group have been working on the technologies to develop more widely protective vaccines for viruses since he joined Georgia Tech in 2015. Although the team didn’t specifically foresee Covid-19 arising when it did, pandemics have regularly occurred throughout human history. While the team pivoted their vaccine research to address coronaviruses, they were surprised by how rapidly each new variant arose, making their broader vaccine even more necessary.
Once they realized the challenge inherent in how fast SARS-CoV-2 mutates, they had two options for how to build a vaccine: design one to be widely preventative against the virus, or use the influenza vaccine, which updates annually for the anticipated prevalent variant, as a model.
Making a broad vaccine is more appealing because it enables patients to get one shot and be protected for years. To create their general vaccine, Kane’s team capitalized on the key to the original mRNA vaccines — the spike protein, which binds the virus to healthy cells. Their vaccine uses three prominent spike proteins, or a trivalent vaccine, to elicit a broad enough antibody response to make the vaccine effective against SARS-CoV-2 variants as well as other sarbecoviruses that have been identified as having pandemic potential.
“If you know which variant is circulating, you can immunize with the spike protein of that variant,” Ph.D. student and co-author Kathryn Loeffler said. “But a broad vaccine is more difficult to develop because you’re protecting against many different antigens versus just one.”
Collaborators in the Kawaoka group at the University of Wisconsin tested their vaccine in hamsters, which they had previously identified as an appropriate animal model to evaluate vaccines and immunotherapies against SARS-CoV-2. The vaccine was able to neutralize all SARS-CoV-2 omicron variants tested, as well as non-SARS-CoV-2 coronaviruses circulating in bats. Even better, the vaccine provided complete protection with no detectable virus in the lungs.
Kane hopes that the vaccine strategy his team identified can be applied to other viruses — other coronavirus subfamilies as well as other viruses such as influenza viruses. They also expect that some of the specific antigens they describe in this paper can be moved toward preclinical trials. Someday, a trivalent vaccine could comprise a routine part of people’s medical treatment.

Mayo Clinic scientists have developed an immunotherapy strategy that potentially lays the groundwork for treating a spectrum of autoimmune diseases.
The new technique, detailed in a preclinical study published in Nature Biomedical Engineering, involves combining chimeric antigen receptors (CAR) with mesenchymal stromal cells (MSC), resulting in engineered stem cells known as CAR-MSCs.
“The pioneering approach shows potential in targeting inflammatory disease sites more precisely and improving immunosuppression and healing outcomes,” says Saad Kenderian, M.B., Ch.B., a principal investigator and hematologist at Mayo Clinic. “We’re planning to study interventions that minimize the need for long-term medications for autoimmune diseases.”
The combination approach centers on mesenchymal stromal cells, which are found in various tissues in the body, including bone marrow, fat tissue and umbilical cord blood. These cells have the unique ability to transform into several specific types of cells such as bone cells, cartilage cells and fat cells.
Mesenchymal stromal cells are known for calming down the immune system, controlling inflammation and promoting immune tolerance to prevent the body’s own tissues from being attacked.
Within this CAR-MSCs framework, mesenchymal stromal cells are engineered with chimeric antigen receptors, which are molecular tools engineered to recognize specific disease-related markers.
Chimeric antigen receptors have three crucial functions: 1) Target and attach to specific markers on diseased cells. 2) Act as an anchor to ensure the chimeric antigen receptors stay connected to the target. 3) Initiate signaling to activate a robust immune response.

While mesenchymal stromal cells have been extensively studied in isolation in autoimmune contexts, their efficacy has fallen short. The combined CAR-MSC therapeutic strategy tackles two key challenges: Mesenchymal stromal cells by themselves have difficulty calming down the strong immune reactions in autoimmune conditions, and they struggle to travel to and attach to the areas of inflammation.
Engineering mesenchymal stromal cells with chimeric antigen receptors shows potential in enhancing their ability to target specific cells or markers and improve their therapeutic impact.
How CAR-MSCs target inflammation
For the study, Dr. Kenderian and his team developed CAR-MSCs to specifically target a protein linked to a condition called graft-versus-host disease, as well as inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease.
Graft-versus-host disease occurs when cells from a donor attack the tissues of the person receiving them, typically following a bone marrow or stem cell transplant.
In mouse models, upon stimulation by the specific protein they were designed to target, CAR-MSCs showed improved ability to go to the inflamed area, have better control of inflammation and improve outcomes and survival. This was mediated by a change in the genetic signature of CAR-MSCs, the proteins they released and receptor expression.
Dr. Kenderian emphasizes that these preliminary findings set the stage for future applications of this technology, paving the way to enhance the therapy’s versatility to address various diseases across the autoimmune spectrum.
This study builds upon a series of previously published studies on CAR-T therapy led by Dr. Kenderian and his collaborators at Mayo Clinic’s Center for Individualized Medicine, Center for Regenerative Biotherapeutics and the Mayo Clinic Comprehensive Cancer Center. Dr. Kenderian is also investigating ways to make CAR-T cell therapy more accessible to patients through on-site biomanufacturing at Mayo Clinic’s campuses in Rochester, Minnesota and Jacksonville, Florida.
Review the study for a complete list of authors, disclosures and funding.

Scientists at Uppsala University have discovered a new class of antibiotics with potent activity against multi-drug resistant bacteria, and have shown that it cures bloodstream infections in mice. The new antibiotic class is described in an article in the scientific journal PNAS.
Antibiotics are the foundation of modern medicine and over the last century have dramatically improved the lives of people around the world. Nowadays we tend to take antibiotics for granted and rely heavily on them to treat or prevent bacterial infections, including for example, to reduce the risk of infections during cancer therapy, during invasive surgery and transplants, and in mothers and preterm babies. Increasingly though, the global rise in antibiotic resistance threatens their effectiveness. In order to ensure access to effective antibiotics in the future, development of novel therapeutics to which there is no existing resistance is essential.
Researchers at Uppsala University have recently published their work in the Proceedings of the National Academy of Sciences of the USA describing a new class of antibiotics developed as a part of multi-national consortia. The class of compounds they describe target a protein, LpxH, which is used in a pathway by Gram-negative bacteria to synthesize their outermost layer of protection from the environment, called lipopolysaccharide. Not all bacteria produce this layer, but those that do include the organisms that have been identified by the World Health Organization as being the most critical to develop novel treatments for, including Escherichia coli and Klebsiella pneumoniae that have already developed resistance to available antibiotics. The researchers were able to show that this new antibiotic class is highly active against multidrug-resistant bacteria and was able to treat bloodstream infections in a mouse model, demonstrating the promise of this class. Importantly, since this compound class is completely new and the protein LpxH has not yet been exploited as a target for antibiotics there is no pre-existing resistance to this class of compounds. This is in contrast to the many ‘me-too’ antibiotics of existing classes currently in clinical development. While the current results are very promising there will be considerable additional work required before compounds of this class will be ready for clinical trials.
The work to discover and develop this new class of antibiotics was supported by the EU project ENABLE which was funded through the Innovative Medicines Initiative’s New Drugs 4 Bad Bugs program (ND4BB). The ENABLE project, led by researchers at Uppsala University and the pharmaceutical company GlaxoSmithKline, brought together stakeholders from across Europe representing academia and large and small pharmaceutical companies to pool resources and expertise to advance early-stage antibiotic development. This antibiotic class now continues to be developed in the follow-on project, ENABLE-2, an antibiotic drug discovery platform funded by Swedish Research Council, the National Research Programme on Antibiotic Resistance and Sweden’s innovation agency Vinnova to continue the momentum generated by the original ENABLE project.

Published15 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Madeline HalpertBBC NewsA person in Texas has tested positive for bird flu, the second US human case of the virus that has infected herds of dairy cows in recent weeks. State health officials said the patient had experienced eye redness after coming into contact with sick cows. The risk to the general public is low, experts said, but people should take precautions when around ill animals.The Texas patient is being treated with an antiviral drug and is isolating.Despite its name, the virus is not limited to birds, and in recent weeks it has been detected in cows in several states, including Texas, Kansas and Michigan. It does not normally spread to people, but human infections have occurred in rare cases around the world.In people, the virus, also known as avian flu, can cause symptoms that range from mild illness, such as upper respiratory and eye infections, to severe disease such as pneumonia that can be fatal, according to the Centers for Disease Control (CDC).The first human case of H5N1 bird flu in the US occurred in 2022 in Colorado, when a person became ill after direct exposure to poultry presumed to be infected. That person experienced fatigue for a few days and made a full recovery. While avian flu is often fatal in poultry, it has been less lethal for cattle. The CDC advises people to avoid exposure to sick or dead animals including wild birds, poultry and cattle. The agency also says people should not eat uncooked or undercooked related food products such as unpasteurized milk and cheeses. More on this storyWhat is bird flu and what’s behind the outbreak?Published23 May 2023Bird flu infects penguins at famous wildlife havenPublished11 March

Nearly every modern cellphone has a built-in compass, or magnetometer, that detects the direction of Earth’s magnetic field, providing critical information for navigation. Now a team of researchers at the National Institute of Standards and Technology (NIST) has developed a technique that uses an ordinary cellphone magnetometer for an entirely different purpose — to measure the concentration of glucose, a marker for diabetes, to high accuracy.
The same technique, which uses the magnetometer in conjunction with magnetic materials designed to change their shape in response to biological or environmental cues, could be used to rapidly and cheaply measure a host of other biomedical properties for monitoring or diagnosing human disease. The method also has the potential to detect environmental toxins, said NIST scientist Gary Zabow.
In their proof-of-concept study, Zabow and fellow NIST researcher Mark Ferris clamped to a cellphone a tiny well containing the solution to be tested and a strip of hydrogel — a porous material that swells when immersed in water. The researchers embedded tiny magnetic particles within the hydrogel, which they had engineered to react either to the presence of glucose or to pH levels (a measure of acidity) by expanding or contracting. Changing pH levels can be associated with a variety of biological disorders.
As the hydrogels enlarged or shrunk, they moved the magnetic particles closer to or farther from the cellphone’s magnetometer, which detected the corresponding changes in the strength of the magnetic field. Employing this strategy, the researchers measured glucose concentrations as small as a few millionths of a mole (the scientific unit for a certain number of atoms or molecules in a substance). Although such high sensitivity is not required for at-home monitoring of glucose levels using a drop of blood, it might in the future enable routine testing for glucose in saliva, which contains a much smaller concentration of the sugar.
The researchers reported their findings in the March 30, 2024 edition of Nature Communications.
Engineered, or “smart,” hydrogels like the ones the NIST team employed are inexpensive and relatively easy to fabricate, Ferris said, and can be tailored to react to a host of different compounds that medical researchers may want to measure. In their experiments, he and Zabow stacked single layers of two different hydrogels, each of which contracted and expanded at different rates in response to pH or glucose. These bilayers amplified the motion of the hydrogels, making it easier for the magnetometer to track changes in magnetic field strength.
Because the technique does not require any electronics or power source beyond that of the cellphone nor call for any special processing of the sample, it offers an inexpensive way to conduct testing — even in locations with relatively few resources.

Future efforts to improve the accuracy of such measurements using cellphone magnetometers might allow detection of DNA strands, specific proteins and histamines — compounds involved in the body’s immune response — at concentrations as low as a few tens of nanomoles (billionths of a mole).
That improvement could have substantial benefit. For instance, measuring histamines, which are typically detected in urine at concentrations ranging from about 45 to 190 nanomoles, would ordinarily require a 24-hour urine collection and a sophisticated laboratory analysis.
“An at-home test using a cellphone magnetometer sensitive to nanomolar concentrations would allow measurements to be done with much less hassle,” said Ferris. More generally, enhanced sensitivity would be essential when only a small amount of a substance is available for testing in extremely dilute quantities, Zabow added.
Similarly, the team’s study suggests that a cellphone magnetometer can measure pH levels with the same sensitivity as a thousand-dollar benchtop meter but at a fraction of the cost. A home-brewer or a baker could use the magnetometer to quickly test the pH of various liquids to perfect their craft, and an environmental scientist could measure the pH of ground water samples on-site with higher accuracy than a litmus test strip could provide.
In order to make the cellphone measurements a commercial success, engineers will need to develop a method to mass produce the hydrogel test strips and ensure that they have a long shelf life, Zabow said. Ideally, he added, the hydrogel strips should be designed to react more quickly to environmental cues in order to speed up measurements.

University of Virginia School of Medicine researchers have discovered a gene on the Y chromosome that contributes to the greater incidence of heart failure in men.
Y chromosome loss in men occurs progressively throughout life and can be detected in approximately 40% of 70-year-old men. UVA’s Kenneth Walsh, PhD, discovered in 2022 that this loss can contribute to heart muscle scarring and lead to deadly heart failure. (That finding was the first to directly link Y chromosome loss to a specific harm to men’s health; Y chromosome loss is increasingly thought to play a role in diseases ranging from Alzheimer’s to cancer.)
In an important follow-up finding, Walsh and his team have discovered how Y chromosome loss triggers changes in heart immune cells that make the cells more likely to cause scarring and heart failure.
Further, the researchers found they could reverse the harmful heart changes by giving lab mice a drug that targets the process of fibrosis that leads to the heart scarring, which could lead to a similar treatment for men.
“Our previous work identified that it was loss of the entire Y chromosome that contributed to heart disease in men,” said Walsh, the director of UVA’s Hematovascular Biology Center. “This new work identified a single gene on the Y chromosome that can account for the disease-promoting effects of Y chromosome loss.”
About Y Chromosome Loss
Unlike women, who have two X chromosomes, men have an X and a Y. For a long time, the genes found on the Y chromosome were not thought to play important roles in disease. Sex hormones, scientists thought, explained the differences in certain diseases in men and women. But Walsh’s groundbreaking work has helped change that perception. It also suggested an explanation for why heart failure is more common in men than women. (Cardiovascular disease, which includes heart failure, is the leading cause of death worldwide.)
Y chromosome loss occurs in only a small percentage of affected men’s cells. This results in what is called “mosaicism,” where genetically different cells occur within one individual. Researchers aren’t entirely sure why this partial Y chromosome loss occurs, but predominantly it strikes elderly men and men who smoke compared to those who don’t.

To better understand the effects of Y chromosome loss, Walsh and his team examined genes found on the Y chromosome to determine which might be important to heart scarring. One gene they looked at, Uty, helps control the operating instructions for immune cells called macrophages and monocytes, the scientists determined. When the Uty gene was disrupted, either individually or through Y chromosome loss, that triggered changes in the immune cells in lab mice. Suddenly, the macrophages were much more “pro-fibrotic,” or prone to scarring. This accelerated heart failure as well, the scientists found.
“The identification of a single gene on the Y chromosome provides information about a new druggable target to treat fibrotic diseases,” said Walsh, of UVA’s Division of Cardiovascular Medicine and Robert M. Berne Cardiovascular Research Center.
Walsh and his team were able to prevent the harmful changes in the mice’s macrophages by giving them a specially designed monoclonal antibody. This halted the harmful changes in the heart, suggesting the approach might, with further research, lead to a way to treat or avoid heart failure and other fibrotic diseases in men with Y chromosome loss.
“Currently, we are working with our clinician colleagues in the Division of Cardiovascular Medicine at UVA to assess whether loss of the Y chromosome in men is associated with greater scarring in the heart,” Walsh said. “This research will provide new avenues for understanding the causes of heart disease.”
Based on their findings, Walsh and his team believe that a small group of genes found on the Y chromosome may have big effects on a wide array of diseases. Their new work identifies mechanisms that may lead to this, and they are hopeful that further research will provide a much better understanding of unknown causes of sickness and death in men.
“This research further documents the utility of studying the genetics of mutations that are acquired after conception and accumulate throughout life,” Walsh said. “These mutations appear to be as important to health and lifespan as the mutations that are inherited from one’s parents. The study of these age-acquired mutations represents a new field of human genetics.”
Findings Published

The researchers have published their findings in the scientific journal Nature Cardiovascular Research. The team consisted of Keita Horitani, Nicholas W. Chavkin, Yohei Arai, Ying Wang, Hayato Ogawa, Yoshimitsu Yura, Megan A. Evans, Jesse Cochran, Mark C. Thel, Ariel H. Polizio, Miho Sano, Emiri Miura-Yura, Yuka Arai, Heather Doviak, Arthur P. Arnold, Bradley D. Gelfand, Karen K. Hirschi, Soichi Sano and Walsh. The scientists have no financial interest in the work.
The research was supported by the National Institutes of Health, grants AG073249, HL142650 and HL152174; the National Aeronautics and Space Administration, grant 80NSSC21K0549; the UVA Medical Scientist Training Program, grant T32GM007267; the American Heart Association, grant 23CDA1054358; Grant-in-Aid for Research Activity Start-up grants 21K20879 and 22K08162; the Japanese Heart Failure Society; the Japanese Circulation Society; the Japan Cardiovascular Research Foundation; the SENSHIN Medical Research Foundation; the MSD Life Science Foundation; Novartis; the Kondou Kinen Medical Foundation; and the Bayer Scholarship for Cardiovascular Research.

Attention-Deficit Hyperactivity Disorder (ADHD) is the most common pediatric neurobehavioral disorder with a prevalence of approximately 7%-10% in school-age children. ADHD significantly affects functioning throughout life including academic achievement, social and family relationships and occupational success, predisposing individuals to secondary psychopathology, substance use, justice system involvement and suicide. Fortunately, ADHD is treatable, most effectively with a combination of medication, behavioral therapy and school-based supports. Unfortunately, many children with ADHD go undiagnosed and untreated for years, and sometimes for life, putting those children most at risk for problematic outcomes.
Universal screening for ADHD in pediatrics could improve early identification and treatment of ADHD. Many pediatric practices have successfully implemented universal behavioral health screening with the Pediatric Symptom Checklist (PSC-17) across populations and languages. However, strategies to optimize use of the Attention Subscale of the PSC-17 in primary care pediatrics have not been described.
Researchers at Boston University Chobanian & Avedisian School of Medicine describe a quality improvement initiative to improve screening for ADHD in the primary care pediatric clinic at Boston Medical Center, the largest safety net hospital in New England. “In our clinic, we found that many children who screened positive for attention problems were not receiving a diagnostic evaluation for ADHD,” explained first author Mona S. Doss Roberts, DO, assistant professor of pediatrics at the school. “Despite the fact that delayed and underdiagnosis of ADHD is common, particularly among lower income and racial and ethnic minority youth, to our knowledge this is the first published report of a quality improvement effort specifically to improve screening for ADHD in pediatric primary care,” she said.
The ADHD Detection Quality Improvement (ADQI) initiative was a multicomponent program including 1) developing and teaching a provider decision-making algorithm; 2) adjusting clinic operational/workflow; and 3) optimizing features in our electronic medical record to flag positive screens and facilitate next steps for evaluation. With their initiative, the researchers showed improvement in recognition of positive Attention Subscale scores on the PSC-17 and evaluation for ADHD with a follow up diagnostic evaluation tool.
According to the researchers, their initiative led to improved clinician recognition of positive screens for attention problems and follow up evaluation for ADHD by distributing diagnostic rating scales to these families. Thus, even in a clinic that had excellent rates of universal behavioral health screening in primary care, were able to optimize use of the tool as a screener for ADHD, improving the likelihood that providers would recognize and document the positive attention problems score as an indication of possible ADHD.
“Despite our initial success, additional interventions are needed to improve the completion of ADHD evaluations in primary care to ensure that children are appropriately identified and offered evidence-based care,” added Roberts, who also is a pediatrician at Boston Medical Center.
These findings appear online in the Journal of Developmental & Behavioral Pediatrics.
Last author Andrea Spencer, MD,currently receives grant funding from the Klingenstein Third Generation Foundation, the Charles H. Hood Foundation, and the National Institute of Mental Health. Other authors report no conflicts of interest.

For people living with serious mental illness like schizophrenia or bipolar disorder, standard treatment with antipsychotic medications can be a double-edged sword. While these drugs help regulate brain chemistry, they often cause metabolic side effects such as insulin resistance and obesity, which are distressing enough that many patients stop taking the medications.
Now, a pilot study led by Stanford Medicine researchers has found that a ketogenic diet not only restores metabolic health in these patients as they continue their medications, but it further improves their psychiatric conditions. The results, published March 27 in Psychiatry Research, suggest that a dietary intervention can be a powerful aid in treating mental illness.
“It’s very promising and very encouraging that you can take back control of your illness in some way, aside from the usual standard of care,” said Shebani Sethi, MD, associate professor of psychiatry and behavioral sciences and the first author of the new paper.
The senior author of the paper is Laura Saslow, PhD, associate professor of health behavior and biological sciences at the University of Michigan.
Making the connection
Sethi, who is board certified in obesity and psychiatry, remembers when she first noticed the connection. As a medical student working in an obesity clinic, she saw a patient with treatment-resistant schizophrenia whose auditory hallucinations quieted on a ketogenic diet.
That prompted her to dig into the medical literature. There were only a few, decades-old case reports on using the ketogenic diet to treat schizophrenia, but there was a long track record of success in using ketogenic diets to treat epileptic seizures.

“The ketogenic diet has been proven to be effective for treatment-resistant epileptic seizures by reducing the excitability of neurons in the brain,” Sethi said. “We thought it would be worth exploring this treatment in psychiatric conditions.”
A few years later, Sethi coined the term metabolic psychiatry, a new field that approaches mental health from an energy conversion perspective.
Meat and vegetables
In the four-month pilot trial, Sethi’s team followed 21 adult participants who were diagnosed with schizophrenia or bipolar disorder, taking antipsychotic medications, and had a metabolic abnormality — such as weight gain, insulin resistance, hypertriglyceridemia, dyslipidemia or impaired glucose tolerance. The participants were instructed to follow a ketogenic diet, with approximately 10% of the calories from carbohydrates, 30% from protein and 60% from fat. They were not told to count calories.
“The focus of eating is on whole non-processed foods including protein and non-starchy vegetables, and not restricting fats,” said Sethi, who shared keto-friendly meal ideas with the participants. They were also given keto cookbooks and access to a health coach.
The research team tracked how well the participants followed the diet through weekly measures of blood ketone levels. (Ketones are acids produced when the body breaks down fat — instead of glucose — for energy.) By the end of the trial, 14 patients had been fully adherent, six were semi-adherent and only one was non-adherent.

Feeling better
The participants underwent a variety of psychiatric and metabolic assessments throughout the trial.
Before the trial, 29% of the participants met the criteria for metabolic syndrome, defined as having at least three of five conditions: abdominal obesity, elevated triglycerides, low HDL cholesterol, elevated blood pressure and elevated fasting glucose levels. After four months on a ketogenic diet, none of the participants had metabolic syndrome.
On average, the participants lost 10% of their body weight; reduced their waist circumference by 11% percent; and had lower blood pressure, body mass index, triglycerides, blood sugar levels and insulin resistance.
“We’re seeing huge changes,” Sethi said. “Even if you’re on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, the insulin resistance. I think that’s very encouraging for patients.”
The psychiatric benefits were also striking. On average, the participants improved 31% on a psychiatrist rating of mental illness known as the clinical global impressions scale, with three-quarters of the group showing clinically meaningful improvement. Overall, the participants also reported better sleep and greater life satisfaction.
“The participants reported improvements in their energy, sleep, mood and quality of life,” Sethi said. “They feel healthier and more hopeful.”
The researchers were impressed that most of the participants stuck with the diet. “We saw more benefit with the adherent group compared with the semi-adherent group, indicating a potential dose-response relationship,” Sethi said.
Alternative fuel for the brain
There is increasing evidence that psychiatric diseases such as schizophrenia and bipolar disorder stem from metabolic deficits in the brain, which affect the excitability of neurons, Sethi said.
The researchers hypothesize that just as a ketogenic diet improves the rest of the body’s metabolism, it also improves the brain’s metabolism.
“Anything that improves metabolic health in general is probably going to improve brain health anyway,” Sethi said. “But the ketogenic diet can provide ketones as an alternative fuel to glucose for a brain with energy dysfunction.”
Likely there are multiple mechanisms at work, she added, and the main purpose of the small pilot trial is to help researchers detect signals that will guide the design of larger, more robust studies.
As a physician, Sethi cares for many patients with both serious mental illness and obesity or metabolic syndrome, but few studies have focused on this undertreated population.
She is founder and director of the metabolic psychiatry clinic at Stanford Medicine.
“Many of my patients suffer from both illnesses, so my desire was to see if metabolic interventions could help them,” she said. “They are seeking more help. They are looking to just feel better.”
Researchers from the University of Michigan; the University of California, San Francisco; and Duke University contributed to the study.
The study was supported by Baszucki Group Research Fund, Keun Lau Fund and the Obesity Treatment Foundation.

Imagine playing a racing game like Mario Kart, using only your brain to execute the complex series of turns in a lap.
This is not a video game fantasy, but a real program that engineers at The University of Texas at Austin have created as part of research into brain-computer interfaces to help improve the lives of people with motor disabilities. More importantly, the researchers incorporated machine learning capabilities with their brain-computer interface, making it a one-size-fits-all solution.
Typically, these devices require extensive calibration for each user — every brain is different, both for healthy and disabled users — and that has been a major hurdle to mainstream adoption. This new solution can quickly understand the needs of an individual subject and self-calibrate through repetition. That means multiple patients could use the device without needing to tune it to the individual.
“When we think about this in a clinical setting, this technology will make it so we won’t need a specialized team to do this calibration process, which is long and tedious,” said Satyam Kumar, a graduate student in the lab of José del R. Millán, a professor in the Cockrell School of Engineering’s Chandra Family Department of Electrical and Computer Engineering and Dell Medical School’s Department of Neurology. “It will be much faster to move from patient to patient.”
The research on the calibration-free interface is published in PNAS Nexus.
From left to right: Satyam Kumar, Hussein Alawieh and José del R. Millán.
The subjects wear a cap packed with electrodes that is hooked up to a computer. The electrodes gather data by measuring electrical signals from the brain, and the decoder interprets that information and translates it into game action.

Millán’s work on brain-computer interfaces helps users guide and strengthen their neural plasticity, the ability of the brain to change, grow and reorganize over time. These experiments are designed to improve brain function for patients and use the devices controlled by brain-computer interfaces to make their lives easier.
In this case, the actions were twofold: the car racing game, and a simpler task of balancing the left and right sides of a digital bar. An expert was trained to develop a “decoder” for the simpler bar task that makes it possible for the interface to translate brain waves into commands. The decoder serves as a base for the other users and is the key to avoiding the long calibration process.
The decoder worked well enough that subjects trained simultaneously for the bar game and the more complicated car racing game, which required thinking several steps ahead to make turns.
The researchers called this work foundational, in that it sets the stage for further brain-computer interface innovation. This project used 18 subjects with no motor impairments. Eventually, as they continue down this road, they will test this on people with motor impairments to apply it to larger groups in clinical settings.
“On the one hand, we want to translate the BCI to the clinical realm to help people with disabilities; on the other, we need to improve our technology to make it easier to use so that the impact for these people with disabilities is stronger,” Millán said.
On the side of translating the research, Millán and his team continue to work on a wheelchair that users can drive with the brain-computer interface. At the South by Southwest Conference and Festivals this month, the researchers showed off another potential use of the technology, controlling two rehabilitation robots for the hand and arm. This was not part of the new paper but a sign of where this technology could go in the future. Several people volunteered and succeeded in operating the brain-controlled robots within minutes.
“The point of this technology is to help people, help them in their everyday lives,” Millán said. “We’ll continue down this path wherever it takes us in the pursuit of helping people.”

UCSF-led research shows smartphone cognitive testing is comparable to gold-standard methods; may detect FTD in gene carriers before symptoms start.
A smartphone app could enable greater participation in clinical trials for people with frontotemporal dementia (FTD), a devastating neurological disorder that often manifests in midlife.
Research into the condition has been hampered by problems with early diagnosis and difficulty tracking how people are responding to treatments that are only likely to be effective at the early stages of disease.
To address this, a research team led by UC San Francisco deployed cognitive tests through a mobile app and found it could detect early signs of FTD in people who were genetically predisposed to get the disease but had not yet developed symptoms. These tests were at least as sensitive as neuropsychological evaluations done in the clinic.
The study appears in JAMA Network Open on April 1, 2024.
More than 30 FTD clinical trials are underway or in the planning stages, including one that may become the first drug approved to slow progression in some gene carriers. Researchers hope the new mobile technology will hasten the work.
“Eventually, the app may be used to monitor treatment effects, replacing many or most in-person visits to clinical trials’ sites,” said first author Adam Staffaroni, PhD, clinical neuropsychologist and associate professor in the UCSF Department of Neurology and the Weill Institute for Neurosciences.

FTD is the No. 1 cause of dementia in patients under 60, with up to 30% of cases attributed to genetics. It has three main variants with symptoms that may overlap. The most common causes dramatic personality shifts, which may manifest as lack of empathy, apathy, impulsivity, compulsive eating, and socially and sexually inappropriate behavior. Another affects movement, and a third impacts speech, language and comprehension, which is the variant that Bruce Willis is reported to have. In rare cases, FTD triggers bursts of visual creativity.
FTD is not easy to diagnose
As with Alzheimer’s disease, patients with FTD are believed to be most responsive to treatment early on, ideally before their symptoms even emerge. “Most FTD patients are diagnosed relatively late in the disease, because they are young, and their symptoms are mistaken for psychiatric disorders,” said senior author Adam Boxer, MD, PhD, endowed professor in memory and aging at the UCSF Department of Neurology.
“We’ve heard from families that they often suspect their loved one has FTD long before a physician agrees that is the diagnosis,” said Boxer, who is also director of the UCSF Alzheimer’s Disease and Frontotemporal Dementia Clinical Trials Program.
The researchers tracked 360 participants with an average age of 54 enrolled in ongoing studies at ALLFTDcenters and UCSF. About 90% had data on disease stage. These included 60% who did not have FTD or were gene carriers who had not yet developed symptoms, 20% with early signs of the disease and 21% with symptoms.
Software that can detect a waning ability to plan
Staffaroni and Boxer collaborated with software company Datacubed Health, which developed the platform, to include tests of executive function, such as planning and prioritizing, filtering distractions and controlling impulses. In FTD, the part of the brain responsible for executive functioning shrinks as the disease progresses.

The rich data collected by the app, including voice recordings and body movements, enabled the researchers to develop new tests that eventually could help with early diagnosis and monitoring of symptoms.
“We developed the capability to record speech while participants engaged with several different tests,” said Staffaroni. “We also created tests of walking, balance and slowed movements, as well as different aspects of language.”
FTD researchers say they are closer to finding treatments that may eventually slow the progression of the disease, which is fatal. These include gene and other therapies, such as antisense oligonucleotides (ASOs), to increase or decrease the production of proteins that are abnormal in gene carriers.
Although there are currently no plans to make the app available to the public, it could be a boon to research.
“A major barrier has been a lack of outcome measures that can be easily collected and are sensitive to treatment effects at early stages of the disease,” said Staffaroni. “We hope that smartphone assessments will facilitate new trials of promising therapies.”