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Published14 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Chloe KimBBC NewsMelatonin use is becoming “exceedingly common” among American children, with nearly one in five under age 14 now consuming melatonin to aid sleep. Parents are increasingly giving it to younger children. About 18% of children age five to nine are using it as a sleep aid, a new study suggests.Last year, the American Academy of Sleep Medicine issued a health advisory about melatonin use for young people.They said parents should consult a doctor before giving it to children.Melatonin is a hormone produced in the brain that regulates a person’s sleep cycle. It is one of the most common supplements parents in the US give to their children, according to Harvard Health.In the US, melatonin is considered a dietary supplement – unlike in many countries, where it is classified as a drug – and can be bought without a prescription. Research in the journal JAMA Pediatrics, published this month, spoke to parents of 993 children, ages one to 14, and found a significant increase in the reported use of melatonin in recent years.Though melatonin can be a short-term solution to help promote sleep, the study indicated that parents were using melatonin regularly, with pre-schoolers taking the supplement for a median of 12 months, primary school aged children for 18 months and pre-teens for 21 months. The authors caution that the study was relatively small and does not necessarily represent usage nationwide.Still, melatonin use, across all ages, has been on the rise for the past couple decades. An online survey earlier this year by the American Academy of Sleep Medicine suggested that about 46% of parents have given melatonin to children under the age of 13 to help them sleep. The survey also found that fathers are more likely to give kids melatonin than mothers and younger parents are more likely to provide the sleep aid than older parents. Poison control centres in the US saw a 530% spike in reports of melatonin ingestion in children between 2012-2021, according to the Centers for Disease Control and Prevention. Most cases were accidental and the vast majority of children – over 84% – had no symptoms, though in 1% of the reported cases the children ended up in intensive care. Previous research also suggests that the dose of melatonin in supplements s often differed from the amount indicated on the packaging label – one study found melatonin ranged from less than half to more than four times the amount stated on the label. The science of healthy baby sleepMild side effects – like daytime sleepiness, headache, nausea, and dizziness – sometimes occur from taking melatonin but little is known about the long-term effects of melatonin consumption in children and adolescents. The American Academy of Sleep Medicine advises that parents treat melatonin like any medication and keep it out of reach of children. They also suggest parents consult a paediatric health worker beforehand and note that “sleep problems can be better managed with a change in schedules, habits, or behaviours rather than taking melatonin”. If used, a medical professional should recommend “the melatonin dose and timing” to address a sleep problem.More on this storyGaining weight? You may need more sleepPublished26 February 2022Sleep crisis a serious issue, politicians sayPublished24 SeptemberWhy you should always go to sleep at the same timePublished2 AugustLights on for a bad night’s sleepPublished14 January 2011

Hair products often contain ingredients that easily evaporate, so users may inhale some of these chemicals, potentially posing health repercussions. Now, researchers have studied emissions of these volatile organic compounds (VOCs), including siloxanes, which shine and smooth hair. The scientists report in ACS’ Environmental Science & Technology that using these hair care products can change indoor air composition quickly, and common heat styling techniques — straightening and curling — increase VOC levels even more.
Some prior studies have examined the amounts of siloxanes released from personal care products. But most focused on products that are washed off the body, such as skin cleansers, which might behave differently from products that are left on the hair, like creams or oils. In addition, most previous studies on siloxane emissions haven’t looked at the real-time, rapid changes in indoor air composition that might occur while people are actively styling hair. Nusrat Jung and colleagues wanted to fill in the details about VOCs released from hair products, especially in real-world scenarios such as small bathrooms where they’re typically applied.
The researchers set up a ventilated tiny house where participants used their usual hair products — including creams, sprays and oils — and heated tools. Before, during and after hair styling, the team measured real-time emissions of VOCs including cyclic volatile methyl siloxanes (cVMS), which are used in many hair care products. The mass spectrometry data showed rapid changes in the chemical composition of air in the house and revealed that cVMS accounted for most of the VOCs that were detected. Emissions were influenced by product type and hair length, as well as the type and temperature of the styling tool. Longer hair and higher temperatures released higher amounts of VOCs.
As a result of their findings, the researchers estimated that a person’s potential daily inhalation of one cVMS, known as D5, could reach as much as 20 mg per day. In the experiments, turning on an exhaust fan removed most of the air pollutant from the room within 20 minutes after a hair care routine was completed, but the scientists note that this practice could affect outdoor air quality in densely populated cities. They say studies of the long-term human health impacts of siloxane exposure are urgently needed, because most findings are from animal studies.

A common concern about gender-affirming hormone therapy for transmasculine people is the risk of red blood cell volume changes and erythrocytosis, a high concentration of red blood cells, with the use of prescribed testosterone. However, Mount Sinai researchers have found that testosterone treatment may be safer than previously reported, with results published today in The Journal of Clinical Endocrinology and Metabolism.
Mount Sinai researchers from the Division of Endocrinology and Center for Transgender Medicine and Surgery examined the relationship between the use of testosterone as part of gender-affirming hormone therapy (GAHT) for transmasculine individuals and changes in hematocrit, a test that measures how much of a person’s blood is made up of red blood cells. The study of a large North American cohort is the largest on this subject to date.
“A major concern of patients, providers, and parents is the safety of hormone therapy for transgender and gender-diverse people. The findings from this study represent very important reassurance regarding the safety of testosterone as masculinizing treatment,” said Joshua Safer, MD, FACP, FACE, Executive Director of the Mount Sinai Center for Transgender Medicine and Surgery, Professor of Medicine at the Icahn School of Medicine at Mount Sinai, and senior author of the report. “Providers should feel more comfortable prescribing testosterone when it is indicated. Patients and the families of patients should feel reassured regarding at least this one source of anxiety about treatment.”
The researchers conducted a cross-sectional analysis of serum-based testosterone and hematocrit levels in 6,670 transmasculine patients who were prescribed testosterone for GAHT through Plume, a virtual provider of gender-affirming care across 45 states. Patients were included if they had an active prescription from Plume for a testosterone product as part of their GAHT regimen, and recent hematocrit and testosterone laboratory values available for analysis. The total testosterone was measured using liquid chromatography-mass spectrometry, and hematocrit was calculated as part of a complete blood count. The hematocrit and testosterone laboratory values were collected as part of the same blood sample, typically mid-week after a weekly injection, for all patients using injectable forms of testosterone.
Researchers found that higher testosterone levels were associated with higher hematocrit levels, however, the magnitude of change in hematocrit was small and unlikely to be clinically meaningful. Only 8.4 percent of transmasculine individuals in the study had a hematocrit greater than 50 percent, and less than 1 percent had a hematocrit greater than 54 percent, the level at which treatment for erythrocytosis is recommended, often through the use of phlebotomy (bloodletting). These numbers are lower than those previously reported in smaller studies, and the finding of such a small degree of change in hematocrit and a lower risk of erythrocytosis should provide more assurance to those prescribing and using testosterone as GAHT.
“Our study found that the numbers of patients on testosterone therapy with abnormal red blood cell elevations were lower than previously reported in smaller studies. It’s noteworthy that in the largest North American cohort reported to date, less than 1 percent of transmasculine individuals had a hematocrit level where medical interventions might be required. These results should help providers feel more comfortable prescribing testosterone as part of GAHT,” said the first and corresponding author, Nithya Krishnamurthy, a second-year medical student at Icahn Mount Sinai. “This work suggests a need to assess the influence of other factors that can lead to secondary erythrocytosis; such as being overweight, smoking tobacco, or using alcohol.”

The gene-editing technology CRISPR shows early promise as a therapeutic strategy for the aggressive and difficult-to-treat brain cancer known as primary glioblastoma, according to findings of a new study from Gladstone Institutes.
Using a novel technique they’ve dubbed “cancer shredding,” the researchers programmed CRISPR to zero-in on repeating DNA sequences present only in recurrent tumor cells — and then obliterate those cells by snipping away at them. Working with cell lines from a patient whose glioblastoma returned after prior treatments, the team used CRISPR to destroy the tumor cells while sparing healthy cells.
“Glioblastoma is the most common lethal brain cancer, and patients still don’t have any good treatment options,” says Christof Fellmann, PhD, who led the study at Gladstone. “Patients typically receive chemotherapy, radiation, and surgery, but most relapse in matter of months. We wanted to find out if we could do something outside the box that could get around this problem of recurrence.”
Finding the Hidden Code
Cancer treatments rarely kill all tumor cells. In glioblastoma, as with many other highly recurrent cancers, tumor cells that escape treatment develop multiple genetic adaptations, or mutations, that allow them to proliferate. Building from their earlier research, the Gladstone team surmised that these mutated cells have a unique genetic signature that could be targeted.
Using computational methods to analyze whole genomes of cancer cells, the team dove deep into the non-coding DNA to identify repetitive code all of them shared, even if they harbored a different variety of mutations. Then, armed with that data, they were able to guide CRISPR to the mutated cancerous cells and destroy them.
“We see CRISPR as a gateway to a new therapeutic approach that won’t be subject to the possibility of tumor cell escape,” Fellmann says. “Cancer shredding could hold potential not only for glioblastoma, but possibly for other hypermutated tumors.”
The findings, in Cell Reports, are available online prior to being published in the November 28 print edition of the scientific journal. Much of the work was conducted in the lab of Gladstone Senior Investigator Jennifer Doudna, PhD, an author of the paper, who received the 2020 Nobel Prize in Chemistry for her co-discovery of the CRISPR-Cas9 gene editing technology. Also playing a key role in the study was Mitchel Berger, MD, a neurosurgeon and director of the Brain Tumor Center at UCSF, whose team helped secure patient-derived cell samples that bolstered clinical relevance of the results, and Alexendar Perez, MD, PhD, a resident at UCSF who did much of the computational work.

A New Role for CRISPR
Until very recently, CRISPR has been used mainly in the development of therapies or as a valued research tool, but not as a treatment modality in itself. That changed in mid-November when UK regulators approved the first CRISPR-based therapy, which is designed to cure sickle cell disease and beta thalassemia. In the US, the FDA is expected to issue a decision on the same therapeutic approach in early December.
The team behind the new Gladstone study say much work is needed to advance their promising findings into a therapy that’s ready to be tested in patients. Among the remaining challenges are determining how CRISPR should be delivered to patients with glioblastoma, and how to ensure no unintended off-target effects.
But despite the unanswered questions, first author I-Li Tan, PhD — who completed the study as a postdoctoral researcher in Doudna’s Gladstone lab and focused on brain cancer as a PhD student — says she feels hopeful about a disease that has vexed scientists for more than a decade.
“We understand so much today about glioblastoma and its biology, yet the treatment regimens haven’t improved,” Tan says. “Now we have a precise way to target the cells that are driving the cancer, and we hope this may one day lead to a cure.”
The work was supported by the NIH/NIGMS Pathway to Independence Award (K99/R00 GM118909), NIH/NIGMS Maximizing Investigators’ Research Award (ESI R35 GM143124), a UCSF Brain Tumor SPORE CEP Award, a UCSF Brain Tumor SPORE DRP Award, and a generous gift from the UCSF Fishgold Hurwitt Brain Tumor Research Fund.

A new AI (Artificial Intelligence) tool may make it possible to spare breast cancer patients unnecessary chemotherapy treatments by using a more precise method of predicting their outcomes, reports a new Northwestern Medicine study.
AI evaluations of patient tissues were better at predicting the future course of a patient’s disease than evaluations performed by expert pathologists.
The AI tool was able to identify breast cancer patients who are currently classified as high or intermediate risk but who become long-term survivors. That means the duration or intensity of their chemotherapy could be reduced. This is important since chemotherapy is associated with unpleasant and harmful side effects such as nausea, or more rarely, damage to the heart.
Currently pathologist evaluate cancerous cells in a patient’s tissue to determine treatment. But patterns of non-cancerous cells are very important in predicting outcomes, the study showed.
This is the first study to use AI for comprehensive evaluation of both the cancerous and non-cancerous elements of invasive breast cancer.
“Our study demonstrates the importance of non-cancer components in determining a patient’s outcome,” said corresponding study author Lee Cooper, associate professor of pathology at Northwestern University Feinberg School of Medicine. “The importance of these elements was known from biological studies, but this knowledge has not been effectively translated to clinical use.”
The study will be published Nov. 27 in Nature Medicine.

In 2023, about 300,000 U.S. women will receive a diagnosis of invasive breast cancer. About one in eight U.S. women will receive a breast cancer diagnosis in their lifetime.
During diagnosis, a pathologist reviews the cancerous tissue to determine how abnormal the tissue appears. This process, known as grading, focuses on the appearance of cancer cells and has remained largely unchanged for decades. The grade, determined by the pathologist, is used to help determine what treatment a patient will receive.
Many studies of breast cancer biology have shown that the non-cancerous cells, including cells from the immune system and cells that provide form and structure for the tissue, can play an important role in sustaining or inhibiting cancer growth.
Cooper and colleagues built an AI model to evaluate breast cancer tissue from digital images that measures the appearance of both cancerous and non-cancerous cells, as well as interactions between them.
“These patterns are challenging for a pathologist to evaluate as they can be difficult for the human eye to categorize reliably,” said Cooper, also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “The AI model measures these patterns and presents information to the pathologist in a way that makes the AI decision-making process clear to the pathologist.”
The AI system analyzes 26 different properties of a patient’s breast tissue to generate an overall prognostic score. The system also generates individual scores for the cancer, immune and stromal cells to explain the overall score to the pathologist. For example, in some patients, a favorable prognosis score may be due to properties of their immune cells, where for others it may be due to properties of their cancer cells. This information could be used by a patient’s care team in creating an individualized treatment plan.

Adoption of the new model could provide patients diagnosed with breast cancers with a more accurate estimate of the risk associated with their disease, empowering them to make informed decisions about their clinical care, Cooper said.
Additionally, this model may help in assessing therapeutic response, allowing treatment to be escalated or de-escalated depending on how the microscopic appearance of the tissue changes over time. For example, the tool may be able to recognize the effectiveness of a patient’s immune system in targeting the cancer during chemotherapy, which could be used to reduce the duration or intensity of chemotherapy.
“We also hope that this model could reduce disparities for patients who are diagnosed in community settings,” Cooper said. “These patients may not have access to a pathologist who specializes in breast cancer, and our AI model could help a generalist pathologist when evaluating breast cancers.”
How the study worked
The study was conducted in collaboration with the American Cancer Society (ACS) which created a unique dataset of breast cancer patients through their Cancer Prevention Studies. This dataset has representation of patients from over 423 U.S. counties, many who received a diagnosis or care at community medical centers. This is important, because most studies typically use data from large academic medical centers which represent only a portion of the U.S. population. In this collaboration, Northwestern developed the AI software while scientists at the ACS and National Cancer Institute provided expertise on breast cancer epidemiology and clinical outcomes.
To train the AI model, scientists required hundreds of thousands of human-generated annotations of cells and tissue structures within digital images of patient tissues. To achieve this, they created an international network of medical students and pathologists across several continents. These volunteers provided this data through a website over the course of several years to make it possible for the AI model to reliably interpret images of breast cancer tissue.
Next the scientists will evaluate this model prospectively to validate it for clinical use. This coincides with the transition to using digital images for diagnosis at Northwestern Medicine, which will happen over the next three years.
The scientists also are working to develop models for more specific types of breast cancers like triple-negative or HER2-positive. Invasive breast cancer encompasses several different categories, and the important tissue patterns may vary across these categories.
“This will improve our ability to predict outcomes and will provide further insights into the biology of breast cancers,” Cooper said.
Other Northwestern authors include Mohamed Amgad Tageldin, Kalliopi Siziopikou and Jeffery Goldstein.
This research was supported by grants U01CA220401 and U24CA19436201 from the National Cancer Institute of the U.S. National Institutes of Health.

Study shows cognitive improvements when participants keep active and socially engaged, control blood pressure and diabetes.
As more medications move towards federal approval for Alzheimer’s disease, a new study led by researchers at UC San Francisco and Kaiser Permanente Washington has found that personalized health and lifestyle changes can delay or even prevent memory loss for higher-risk older adults.
The two-year study compared cognitive scores, risk factors and quality of life among 172 participants, of whom half had received personalized coaching to improve their health and lifestyle in areas believed to raise the risk of Alzheimer’s, such as uncontrolled diabetes and physical inactivity. These participants were found to experience a modest boost in cognitive testing, amounting to a 74% improvement over the non-intervention group.
Improvements were also noted between the two groups in measurements of risk factors and quality of life, translating approximately to 145% and 8%, respectively, the researchers reported. The study publishes Nov. 27, 2023, in JAMA IM.
Older adults highly motivated to make changes
The study, known as SMARRT, for systematic multi-domain Alzheimer’s risk reduction trial, follows previous work from other researchers that has yielded contradictory results on the effects of health and lifestyle interventions. This study differed, though, in providing personal coaching that was customized to each participant.
“This is the first personalized intervention, focusing on multiple areas of cognition, in which risk factor targets are based on a participant’s risk profile, preferences and priorities, which we think may be more effective than a one-size-fits-all approach,” said first author and lead investigator Kristine Yaffe, MD, vice chair of research in psychiatry and professor in the UCSF departments of neurology, psychiatry, and epidemiology and biostatistics.

“In an earlier survey of 600 older adults, we found that most were concerned about Alzheimer’s disease and related dementias. They wanted to know their personal risk factors and were highly motivated to make lifestyle changes to lower dementia risk,” said Yaffe, referring to her collaboration with co-lead investigator and co-author Eric B. Larson, MD, MPH, former vice president for research and health care intervention at Kaiser Permanente Washington.
Participants in the current study, as well as the earlier survey, were enrolled in Kaiser Permanente Washington and were between 70 and 89 years old. They had at least two of eight risk factors for dementia: physical inactivity, uncontrolled hypertension, uncontrolled diabetes, poor sleep, use of prescription medications associated with risk of cognitive decline, high depressive symptoms, social isolation and current smoking status.
The intervention participants met with a nurse and health coach and selected specific risk factors they wanted to address. They received coaching sessions every few months to review their goals, which ranged from tracking hypertension to walking a certain number of steps per day or signing up for a class. The meetings started in person and switched to phone calls during the pandemic.
Non-intervention participants were similar in age, risk factors and cognitive scores and received educational material, mailed every three months, on dementia risk reduction.
Pandemic did not offset study’s positive effects
“We were pleasantly surprised that the positive results of the trial were not offset by the impact of the pandemic,” said Larson, who is currently professor of medicine at University of Washington. “We know that isolation from social distancing took a heavy toll on cognition, social lives, and mental and physical health in some older adults. But participants in the intervention group fared better cognitively and had fewer risk factors after the trial, during the pandemic, than they did before.”
Unlike anti-amyloid medications, risk-reduction programs are not costly, nor do they have strict eligibility criteria or require extensive monitoring for side-effects, said Yaffe, who is also affiliated with the San Francisco VA Health Care System and the UCSF Weill Institute for Neurosciences.
“Hopefully in the future, treatment of Alzheimer’s and related dementias will be like cardiovascular disease management, with a combination of risk-reduction and specific drugs targeted for disease mechanisms,” she said.

An international team has shown that the injection of a type of stem cell into the brains of patients living with progressive multiple sclerosis (MS) is safe, well tolerated and has a long-lasting effect that appears to protect the brain from further damage.
The study, led by scientists at the University of Cambridge, University of Milan Bicocca and Hospital Casa Sollievo della Sofferenza (Italy), is a step towards developing an advanced cell therapy treatment for progressive MS.
Over 2 million people live with MS worldwide, and while treatments exist that can reduce the severity and frequency of relapses, two-thirds of MS patients still transition into a debilitating secondary progressive phase of disease within 25-30 years of diagnosis, where disability grows steadily worse.
In MS, the body’s own immune system attacks and damages myelin, the protective sheath around nerve fibres, causing disruption to messages sent around the brain and spinal cord.
Key immune cells involved in this process are macrophages (literally ‘big eaters’), which ordinarily attack and rid the body of unwanted intruders. A particular type of macrophage known as a microglial cell is found throughout the brain and spinal cord. In progressive forms of MS, they attack the central nervous system (CNS), causing chronic inflammation and damage to nerve cells.
Recent advances have raised expectations that stem cell therapies might help ameliorate this damage. These involve the transplantation of stem cells, the body’s ‘master cells’, which can be programmed to develop into almost any type of cell within the body.
Previous work from the Cambridge team has shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, can help reduce inflammation and may be able to help repair damage caused by MS.

Now, in research published in the Cell Stem Cell, scientists have completed a first-in-man, early-stage clinical trial that involved injecting neural stem cells directly into the brains of 15 patients with secondary MS recruited from two hospitals in Italy. The trial was conducted by teams at the University of Cambridge, Milan Bicocca and the Hospitals Casa Sollievo della Sofferenza and S. Maria Terni (IT) and Ente Ospedaliero Cantonale (Lugano, Switzerland) and the University of Colorado (USA).
The stem cells were derived from cells taken from brain tissue from a single, miscarried fetal donor. The Italian team had previously shown that it would be possible to produce a virtually limitless supply of these stem cells from a single donor — and in future it may be possible to derive these cells directly from the patient — helping to overcome practical problems associated with the use of allogeneic fetal tissue.
The team followed the patients over 12 months, during which time they observed no treatment-related deaths or serious adverse events. While some side-effects were observed, all were either temporary or reversible.
All the patients showed high levels of disability at the start of the trial — most required a wheelchair, for example — but during the 12 month follow up period none showed any increase in disability or a worsening of symptoms. None of the patients reported symptoms that suggested a relapse and nor did their cognitive function worsen significantly during the study. Overall, say the researchers, this points to a substantial stability of the disease, without signs of progression, though the high levels of disability at the start of the trial make this difficult to confirm.
The researchers assessed a subgroup of patients for changes in the volume of brain tissue associated with disease progression. They found that the larger the dose of injected stem cells, the smaller the reduction in this brain volume over time. They speculate that this may be because the stem cell transplant dampened inflammation.
The team also looked for signs that the stem cells were having a neuroprotective effect — that is, protecting nerve cells from further damage. Their previous work showed how tweaking metabolism — how the body produces energy — can in turn reprogram microglia from ‘bad’ to ‘good’. In this new study, they looked at how the brain’s metabolism changes after the treatment. They measured changes in the fluid around the brain and in the blood over time and found certain signs that are linked to how the brain processes fatty acids. These signs were connected to how well the treatment works and how the disease develops. The higher the dose of stem cells, the greater the levels of fatty acids, which also persisted over the 12-month period.

Professor Stefano Pluchino from the University of Cambridge, who co-led the study, said: “We desperately need to develop new treatments for secondary progressive MS, and I am cautiously very excited about our findings, which are a step towards developing a cell therapy for treating MS.
“We recognise that our study has limitations — it was only a small study and there may have been confounding effects from the immunosuppressant drugs, for example — but the fact that our treatment was safe and that its effects lasted over the 12 months of the trial means that we can proceed to the next stage of clinical trials.”
Co-leader Professor Angelo Vescovi from the University of Milano-Bicocca said: “It has taken nearly three decades to translate the discovery of brain stem cells into this experimental therapeutic treatment This study will add to the increasing excitement in this field and pave the way to broader efficacy studies, soon to come.”
Caitlin Astbury, Research Communications Manager at the MS Society, says: “This is a really exciting study which builds on previous research funded by us. These results show that special stem cells injected into the brain were safe and well-tolerated by people with secondary progressive MS. They also suggest this treatment approach might even stabilise disability progression. We’ve known for some time that this method has the potential to help protect the brain from progression in MS.
“This was a very small, early-stage study and we need further clinical trials to find out if this treatment has a beneficial effect on the condition. But this is an encouraging step towards a new way of treating some people with MS.”

An intense international effort to improve the resolution of magnetic resonance imaging (MRI) for studying the human brain has culminated in an ultra-high resolution 7 Tesla scanner that records up to 10 times more detail than current 7T scanners and over 50 times more detail than current 3T scanners, the mainstay of most hospitals.
The dramatically improved resolution means that scientists can see functional MRI (fMRI) features 0.4 millimeters across, compared to the 2 or 3 millimeters typical of today’s standard 3T fMRIs.
“The NexGen 7T scanner is a new tool that allows us to look at the brain circuitry underlying different diseases of the brain with higher spatial resolution in fMRI, diffusion and structural imaging, and therefore to perform human neuroscience research at higher granularity. This puts UC Berkeley at the forefront of human neuroimaging research,” said David Feinberg, the director of the project to build the scanner, acting professor at the Helen Wills Neuroscience Institute at the University of California, Berkeley, and president of Advanced MRI Technologies (AMRIT), a research company based in Sebastopol, California.
“The ultra-high resolution scanner will allow research on underlying changes in brain circuitry in a multitude of brain disorders, including degenerative diseases, schizophrenia and developmental disorders, including autism spectrum disorder.”
This next generation or NexGen 7T MRI scanner is described in a paper that will be published Nov. 27 in the journal Nature Methods.
The improved resolution will help neuroscientists probe the neuronal circuits in different regions of the brain’s neocortex and allow researchers to track signals propagating from one area of the cortex to another as we think and reason, and perhaps discover underlying causes of developmental disorders. This could lead to better ways of diagnosing brain disorders, perhaps by identifying new biomarkers that would allow diagnosis of mental disorders earlier or, more specifically, in order to choose the best therapy.
“Normally, MRI is not fast enough at all to see the direction of the information being passed from one area of the brain to another,” Feinberg said. “The scanner’s higher spatial resolution can identify activity at different depths in the brain’s cortex to indirectly reveal brain circuitry by differentiating activity in different cell layers of the cortex.”
This is possible because neuroscientists have found in vision brain areas that the superficial and deepest cortex layers (blue arrows in image on right) incorporate “top-down” circuits, that is, they receive information from higher cortical brain areas, whereas the middle cortex involves “bottom-up” circuitry, receiving input to the brain from our senses. Pinpointing the fMRI activity to a specific depth in the cortex lets neuroscientists track the flow of information throughout the brain and cortex.

With the higher spatial resolution, neuroscientists will be able to home in on the activity of something on the order of 850 individual neurons within a single voxel — a 3D pixel — instead of the 600,000 recorded with standard hospital MRIs, said Silvia Bunge, a UC Berkeley professor of psychology who is one of the first to use the NexGen 7T to conduct research on a human brain.
“We were able to look at the layer profile of the prefrontal cortex, and it’s beautiful,” said Bunge, who studies abstract reasoning. “It’s so exciting to have this state-of-the-art, world-class machine.”
For William Jagust, a UC Berkeley professor of public health who studies the brain changes associated with Alzheimer’s disease, the improved resolution could finally help connect the dots between observed changes due to Alzheimer’s that occur in the brain — abnormal clumps of protein called beta amyloid and tau — and changes in memory.
“We know that part of the memory system in the brain degenerates as we get older, but we know little about the actual changes to the memory system — we can only go so far because of the resolution of our current MRI systems,” said Jagust. “With this new scanner, we think we’re going to be able to take apart a lot more carefully exactly where things have gone wrong. This could help with diagnosis or predicting outcomes in normal people.”
Jack Gallant, a UC Berkeley professor of psychology, hopes the scanner will help neuroscientists discover how functional changes in the brain lead to developmental and mental disorders such as dyslexia, autism and schizophrenia, or that result from neurological disorders, such as dementia and stroke.
“Mental disorders have an enormous impact on individuals, families and society. Together they represent about 10% of the U.S. GDP. Mental disorders are fundamentally disorders of brain function, but functional measures are not used currently to diagnose most brain disorders or to look to see if a treatment’s working. Instead, these disorders are diagnosed behaviorally. This is a weak approach, because there are a lot of different mental brain states that can lead to exactly the same behavior,” Gallant said. “What we need is more powerful MRI machines like this so that we can map, at high resolution, how information is represented in the brain. To me this is the big potential clinical benefit of ultra-high resolution MRI.”
BRAIN Initiative

The breakthrough came about through an initial $13.4 million in funding from the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative of the U.S. National Institutes of Health (NIH). The initiative aims to develop new technologies that will produce a dynamic picture of the brain showing how individual cells and complex neural circuits interact across the brain and over time.
Additional funding from UC Berkeley’s Chancellor’s Office and the Weill Neurohub brought the total funding to over $22 million, which allowed Feinberg to assemble a multidisciplinary team of academics and leading scientists at the multinational corporation Siemens Healtheneers, a major manufacturer of hospital and research MRI scanners; MR CoilTech Limited of Glasgow, Scotland, maker of transmitter and receiver detector coils used in MRI to generate and record signals; and AMRIT, a designer of imaging pulse sequences that control the scanner hardware.
Incorporating newly developed hardware technology from those groups, Siemens collaborated with Feinberg’s team to rebuild a conventional 7 Tesla MRI scanner delivered to UC Berkeley in 2000 to improve the spatial resolution in pictures captured during brain scans.
“There’s been a large increase throughout the world of sites that use 7T MRI scanners, but they were mostly for development and were difficult to use,” said Nicolas Boulant, a physicist visiting from the NeuroSpin project at the University of Paris in Saclay, where he leads the team that operates the world’s only 11.7 Tesla MRI scanner, the strongest magnetic field employed to date. “David’s team really put together many ingredients to make a quantum leap at 7 Tesla, to go beyond what was achievable before and gain performance.”
Boulant hopes to adapt some of the new ingredients in the NexGen 7T — in particular, redesigned gradient coils — to eventually achieve even better resolution with the 11.7 Tesla MRI scanner. The gradient coils generate a rising magnetic field across the brain so that each part of the brain sees a different field strength, which helps to precisely map brain activity.
“The higher the magnetic field, the more difficult it is to really grab the potential promised by these higher-field MRI scanners to see finer details in the human brain,” he said. “You need all this peripheral equipment, which needs to be on steroids to meet those promises. The NexGen 7T is really a game-changer when you want to do neuro MRI.”
To reach higher spatial resolution, the NexGen 7T scanner had to be designed with a greatly improved gradient coil and with larger receiver array coils — which detect the brain signals — using from 64 to 128 channels to achieve a higher signal-to-noise ratio (SNR) in the cortex and faster data acquisition. All these improvements were combined with a higher signal from the ultra-high field 7T magnet to achieve cumulative gains in the scanner performance.
The extremely powerful gradient coil is the first to be made with three layers of wire windings. Designed by Peter Dietz at Siemens in Erlangen, Germany, the “Impulse” gradient has 10 times the performance of gradient systems in current 7T scanners. Mathias Davids, then a physics graduate student at Heidelberg University in Mannheim, Germany, and a member of Feinberg’s team, collaborated with Dietz in performing physiologic modeling to allow a faster gradient slew rate — a measure of how quickly the magnetic field changes across the brain — while remaining under the neuronal stimulation thresholds of the human body.
“It’s designed so that the gradient pulses can be turned on and off much quicker — in microseconds — to record the signals much quicker, and also so the much higher amplitude gradients can be utilized without stimulating the peripheral nerves in the body or stimulating the heart, which are physiologic limitations,” Feinberg said.
A second key development in the scanner, Feinberg said, is the 128-channel receiver system that replaces the standard 32 channels. The large receiver coil arrays built by Shajan Gunamony of MR CoilTech in Glasgow, UK, gave a higher signal-to-noise ratio in the cerebral cortex and also provided higher parallel imaging acceleration for faster data acquisition to encode large image matrices for ultra high resolution fMRI and structural MRI.
To take advantage of the new hardware technology, Suhyung Park, Rüdiger Stirnberg, Renzo Huber, Xiaozhi Cao and Feinberg designed new pulse sequences of precisely timed gradient pulses to rapidly achieve ultra high resolution. The smaller voxels, measured in units of cubic millimeters and less than 0.1 microliter, provide a 3D image resolution that is 10 times higher than that of previous 7T fMRIs and 125 times higher than the typical hospital 3T MRI scanners used for medical diagnosis.
Voxels matter
The most common MRI scanners employ superconducting magnets that produce a steady magnetic field of 3 Tesla — 90,000 times stronger than Earth’s magnetic field.
“A 3T fMRI scanner can resolve spatial details with a resolution of about 2 to 3 mm. The cortical circuits that underpin thought and behavior are about 0.5 mm across, so standard research scanners cannot resolve these important structures,” Gallant said.
In contrast, fMRI focuses on blood flow in arteries and veins and can vividly distinguish oxygenated hemoglobin funneling into working areas of the brain from deoxygenated hemoglobin in less active areas. This allows neuroscientists to determine which areas of the brain are engaged during a specific task.
But again, the 3 mm resolution of a 3T fMRI can distinguish only large veins, not the small ones that could indicate activity within microcircuits.
The NexGen 7T will allow neuroscientists to pinpoint activity within the thin cortical layers in the gray matter, as well as within the narrow column circuits that are organized perpendicular to the layers. These columns are of special interest to Gallant, who studies how the world we see is represented in the visual cortex. He has actually been able to reconstruct what a person is seeing based solely on recordings from the brain’s visual cortex.
“The machine that David has built, in theory, should get down to 500 microns, or something like that, which is way better than anything else — we’re very near the scale you would want if you’re getting signals from a single column, for example,” Gallant said. “It’s fantastic. The whole thing about MRI is how big is the little volumetric unit, the voxel, the three-dimensional pixel that you’re recording from. That’s the only thing that matters.”
For the moment, NexGen 7T brain scanners must be custom-built from regular 7T scanners. The cost should be considerably lower than the $22 million required to build the first one, however. These funds came not only from the BRAIN Initiative, but also from UC Berkeley funds through the Helen Wills Neuroscience Center, with which Feinberg, Bunge, Gallant and Jagust are affiliated.
Feinberg said that UC Berkeley’s NexGen 7T scanner technology will be disseminated by Siemens and MR CoilTech Ltd.
“My view is that we may never be able to understand the human brain on the cellular synaptic circuitry level, where there are more connections than there are stars in the universe,” Feinberg said. ” But we are now able to see signal patterns of brain circuits and begin to tease apart feedback and feed forward circuitry in different depths of the cerebral cortex. And in that sense, we will soon be able to understand the human brain organization better, which will give us a new view into disease processes and ultimately allow us to test new therapies. We are seeking a better understanding and view of brain function that we can reliably test and reproducibly use noninvasively.”
Other co-authors of the paper are Alexander Beckett of Advanced MRI Technologies; Chunlei Liu of UC Berkeley’s Helen Wills Neuroscience Institute; An (Joseph) Vu of UC San Francisco; Lawrence Wald, Bernhard Gruber, Jon Polimeni and Jason Stockmann of the A. A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital; Kawin Setsompop of Stanford University in California; Rudiger Sternberg of the German Center for Neurodegenerative Diseases in Bonn, Germany; Laurentius (Renzo) Huber of Maastricht University in the Netherlands; and Suhyung Park at Chonnam National University, South Korea.
The work was supported by BRAIN Initiative grants through the NIH (U01-EB025162, R01-322 MH111444) and other NIH grants (P41-EB030006, NIH R44-MH129278), as well as by funds from UC Berkeley’s Chancellor’s Office and the Weill Neurohub.

Scientists have developed a potentially transformative new technique that could aid in the discovery and development of new therapeutics for a number of globally prevalent autoimmune diseases.
Conditions such as lupus, rheumatoid arthritis and inflammatory bowel disease (IBD) — as well as failures within transplanted cells — are all caused by altered cytokine secretion of immune cells within the human body.
To find treatments for such diseases, experts need to identify the genetic regulators of the secretion so they can explore the most effective ways of inhibiting them.
An international team of researchers has developed a new method, referred to as Secretion-Enabled Cell Ranking and Enrichment (SECRE) and detailed in a study published in Nature Biomedical Engineering.
They have demonstrated the method is accurate in sorting hundreds of millions of CRISPR-edited cells based on their secretion patterns, and identifying the genetic regulators of cytokine secretion in an autoimmune condition.In addition to this, the method takes into account the detailed profiles of approved treatments, and those under development, to establish if therapies already in existence can be reapplied in new ways.
Writing in the study, the researchers detail how they have validated their approach on the cells known to play an essential role in the development and severity of IBD, and proved it has the potential of finding new ways of treating conditions that impact millions of people globally.
The research is the result of a project lasting around four years between scientists in the UK, United States and Canada, world-leading experts in engineering new tools for the diagnosis and treatment of disease, led by Professor Shana Kelley, President of the Chan-Zuckerberg Institute and Professor at Northwestern University.

Dr Mahmoud Labib, Lecturer in the University of Plymouth’s Peninsula Medical School, and the main inventor of the approach said: “This is an incredibly novel approach that can potentially deliver huge benefits for patients, clinicians and the drug companies working to establish new treatments. It gives us the ability to sort large number of cells based on their secretion patterns and identify therapeutic targets that could be applied to help those with conditions for which there are currently few therapeutic options. Through our existing work, we have demonstrated there is the potential for it to help identify ways of treating various autoimmune conditions, but my work is also now extending to types of cancer including some of the most aggressive types of brain tumours.”
A potential treatment for inflammatory bowel disease?
Inflammatory bowel disease (IBD) is a long-term health condition that has been estimated to affect around 7million people worldwide. It is characterised by chronic inflammation of the digestive tract, which can result in severe tummy pain and diarrhoea, and there is presently no known cure.
As part of work to validate their approach, the researchers examined the effect of several kinase inhibitors on CD4+ T cells, which are known to produce interferon gamma, a protein widely implicated in several autoimmune diseases including IBD. The inhibitors looked at included XMU-MP1, a small molecule that has previously been explored as a treatment for heart failure, hair loss and a number of other medical conditions.
In this instance, the researchers used XMU-MP1 to treat mice with a form of colitis that has a similar cell secretion profile to that found in humans with IBD. They found the mice experience significantly less weight loss and reduced colitis symptoms, while their colons remained virtually normal in appearance and did not show any significant loss of intestinal stem cells.
Based on these findings, the researchers say their results suggest that using XMU-MP1 as a means to inhibit interferon gamma production in the gut may represent an ideal means to control IBD. They also say it provides a promising future strategy for the therapeutic molecular targeting of the condition, although extensive clinical trials would be required before it could be considered as a treatment.
How the SECRE technique works
The Secretion-Enabled Cell Ranking and Enrichment (SECRE) technique captures the secreted cytokine on the surface of the cell. These cytokines are then labelled with magnetic nanoparticles and sorted at high resolution within a microfluidic device, fabricated using scaled three-dimensional printing.
The SECRE technique enables rapid and high-throughput sorting of cells based on their secretion patterns, which makes it amenable to large-scale functional genetic screens. This approach also links the functional signature of the cell with its phenotype, allowing for selective sorting of specific subsets of immune cells on the basis of specific cell-surface markers as well as the secretion specific factors.

In recent years, cell and gene therapies have shown significant promise for treating cancer, cystic fibrosis, diabetes, heart disease, HIV/AIDS and other difficult-to-treat diseases. But the lack of effective ways to deliver biological treatments into the body has posed a major barrier for bringing these new therapies to the market — and, ultimately, to the patients who need them most.
Now, Northwestern University synthetic biologists have developed a flexible new platform that solves part of this daunting delivery problem. Mimicking natural processes used by viruses, the delivery system binds to target cells and effectively transfers drugs inside.
The workhorses behind this new platform are extracellular vesicles (EVs) — tiny, virus-sized nanoparticles that all cells already naturally produce. In the new study, researchers used the powerful approach of synthetic biology to build DNA “programs” that — when inserted into “producer” cells — direct those cells to self-assemble custom EVs with useful surface features. The programs also direct cells to produce and load the EVs with biological drugs.
In proof-of-concept experiments, the particles successfully delivered biological drugs — in this case CRISPR gene-editing agents that knocked out a receptor used by HIV — to T cells, which are notoriously difficult to target. The researchers also hypothesize the system should work for many drugs and many types of cells.
The research was published today (Nov. 27) in the journal Nature Biomedical Engineering. It marks the first study to successfully use EVs to deliver cargo into T cells.
“The genomics revolution has transformed our understanding of the molecular bases of many diseases, but these insights have not resulted in new medicines for one fundamental reason: We lack the technology needed to deliver targeted medicines to specific sites in the body where they are needed,” said Northwestern’s Joshua N. Leonard, who led the study. “These shared delivery challenges are holding us back. By making broadly enabling delivery platforms available, we can remove a huge amount of risk and cost from bringing new drugs to clinical trials or to market. Instead of designing a new delivery system every time a company makes a new drug, we hope that they can instead use modular, reconfigurable platforms like ours, thus accelerating the rate at which gene and cell therapies are developed and evaluated.”
A synthetic biology pioneer, Leonard is a professor of chemical and biological engineering at Northwestern’s McCormick School of Engineering and a key member of the Center for Synthetic Biology (CSB). Working with Northwestern’s Innovation and New Ventures Office, Leonard launched Syenex in 2022 to help solve drug delivery for cell and gene therapy developers. Syenex is one of 12 startups housed at the Querrey InQbation Lab, Northwestern’s new incubator. The multidisciplinary team includes Julius Lucks, a professor of chemical and biological engineering at McCormick and CSB member, and Judd Hultquist, an assistant professor of medicine (infectious diseases) and microbiology-immunology at Northwestern University Feinberg School of Medicine.

The promises — and challenges — of targeted drug delivery
By replacing faulty genes or delivering healthy new genes or cells into a patient, gene and cell therapies hold promise for treating a wide range of diseases. Using a delivery vehicle, gene therapies enter the body to transfer genetic material into specific cells to treat or prevent disease. Cell therapies use a similar approach but transfer full cells, which are typically modified outside the body before being administered.
In the most successful cases, viral vectors — which use parts derived from viruses but cannot cause an infection — have served as the delivery mechanism for both cell and gene therapies. But this strategy comes with limitations. The immune system sometimes recognizes virus parts as foreign and blocks such vectors before they deliver their cargo.
“Viruses have a natural ability to enter cells and deliver cargo,” Leonard said. “Borrowing viral parts is an effective strategy for achieving delivery, but then you are somewhat limited to the types of delivery that the virus evolved to do. It takes substantial engineering work to tweak those systems to alter their functions for each application. In this story, we instead attempted to mimic the strategy that viruses have evolved, but we used new biological ‘parts’ to overcome some limitations of viral vectors and ultimately make new functionalities possible.”
To design a multifunctional vehicle, the researchers looked to EVs, which Leonard described as “a blank slate.” In all living beings (from yeast to plants to humans), cells naturally shed EVs, which researchers think play an important role in communication among cells and natural processes such as immune function.
“These particles are being shed and taken up by cells all the time — in both healthy and disease processes,” Leonard said. “For example, we know that cancer cells shed EVs, and that seems to be a part of the process by which cancer spreads from one site to another. On the flip side, EVs also transfer samples of invading pathogens from infected cells to immune cells, helping the body marshal an effective response.”
Harnessing a ‘blank slate’

For Leonard’s EV-based platform, his team developed and synthesized custom DNA molecules that were introduced into a producer cell. The DNA provided instructions for the producer cell to produce new biomolecules and then load those molecules onto the surface and inside the interior of EVs. This effectively generated EVs adorned with specifically designed characteristics — and cargo already in tow.
“We treat the EVs produced by cells as essentially blank slates upon which we can compose new functions by engineering those producer cells to express engineered or natural proteins and nucleic acids,” Leonard said. “These alter the EV function and can comprise bioactive, therapeutic cargo.”
To be successful, the EVs must target the correct cells, transfer their cargo into those cells and avoid side effects — all while avoiding the patient’s always vigilant immune system. Compared to viruses, EVs are likely more capable of evading rejection by the immune system. Because EVs can be produced with materials largely found in a patient’s own cells, the body is less likely to treat the particles as a foreign substance.
The T cell challenge
To test the concept, Leonard and his team looked to an attractive yet stubborn target: T cells. Because T cells naturally help the body fight germs and disease, researchers have looked to enhance T cells’ natural abilities for immunotherapy applications.
“Most cells are constantly sampling little bits of their environment,” said the study’s lead author Devin Stranford, a graduate from Leonard’s lab and now a scientist at Syenex. “But, for whatever reason, T cells don’t do that as much. Therefore, it’s challenging to deliver drugs to T cells because they won’t actively take them up. You have to get the biology right in order for those delivery events to occur.”
In the experiments, the researchers engineered a producer cell to generate EVs loaded with Cas9, a protein that is part of the CRISPR system, paired with an engineered RNA molecule to direct it to recognize and alter a specific sequence of DNA in a cell’s genome. The researchers introduced the modified EVs into a culture of T cells. The EVs efficiently bound to the T cells and successfully delivered their cargo, leading to a genetic edit that inactivated the gene encoding a receptor used by HIV to infect T cells. Although treatment of HIV infections was not an immediate goal of this project, this work nonetheless illustrates that promise, demonstrating the types of new therapeutic functions that the technology enables.
“A key goal of this work was using rigorous methods to ensure that the cargo got all the way to where it needed to go,” Leonard said. “Because we’re making edits to the genome of these cells, we can use powerful technologies like next-generation sequencing to confirm that those exact edits were present in the recipient cells, in the location of the genome where they were intended.”
What’s next?
Called GEMINI (Genetically Encoded Multifunctional Integrated Nanovesicles), the new platform represents a suite of technologies for genetically engineering cells to produce multifunctional EVs to address diverse patient needs.
“Depending on the treatment, one might need a billion EVs,” he said. “But because they are so small, it’s actually a tiny amount of material. Others have already demonstrated that EVs can be produced in clinically translatable ways at commercial scale. Indeed, a particular benefit of biologically encoding EV functions, as we have, is that all the complexity goes into engineering the DNA programs. Once that is done, such processes are readily compatible with mature, existing manufacturing methods.”
Through Syenex, Leonard hopes to use the GEMINI platform, alongside other synthetic biology technologies, to rapidly generate best-in-case delivery vehicles that enable developers — ranging from academic spinouts to mature biotechnology companies — to design new, life-changing cell and gene therapies.
“By demonstrating the ability to genetically encode cargo and surface compositions of nanovesicles with the GEMINI platform, we can turn a hard biology problem into an easier DNA engineering problem,” Leonard said. “That enables us to tap into the ongoing exponential improvements in DNA synthesis and sequencing that have powered the growth of synthetic biology. We are optimistic that these approaches will enable researchers to solve the big delivery challenges and develop new and improved treatments that benefit a wide range of patients.”