Researchers at Karolinska Institutet in Sweden have succeeded in delivering targeted cancer treatment via small membrane bubbles that our cells use to communicate. A new study published in Nature Biomedical Engineering shows that the treatment reduces tumour growth and improves survival in mice.
When our cells communicate, they send out small membrane bubbles known as extracellular vesicles which contain various signalling molecules. Interest in these tiny bubbles, sometimes referred to as the body’s ‘message in a bottle’, has increased in recent years as they could be used to deliver medicines.
Antibodies seek out tumours
Researchers at Karolinska Institutet have now created a targeted cancer treatment by loading these bubbles with a chemotherapeutic drug and attaching antibodies against tumours to their surface. In addition to targeting tumour cells, the antibodies act as a form of immunotherapy, resulting in an enhanced therapeutic effect. The treatment reduced tumour growth and improved survival when given as an injection to mice with breast cancer or melanoma.
“By attaching different antibodies to extracellular vesicles, we can target them to virtually any tissue and we can load them with other types of drugs as well,” says Oscar Wiklander, physician and researcher at the Department of Laboratory Medicine, Karolinska Institutet, and joint first author with Doste Mamand, researcher at the same department. “Therefore, the treatment has the potential to be used against other diseases and cancer types.”
More effective and fewer side effects
The hope is that the new treatment will be more specific and effective in eliminating tumour cells without affecting healthy tissue, compared to current treatment strategies. The researchers plan to investigate whether different combinations of antibodies and drugs can further improve treatment.
“Among other things, we want to investigate the possibility of delivering mRNA as an anticancer drug,” says the study’s last author Samir EL Andaloussi, Professor at the Department of Laboratory Medicine, Karolinska Institutet. “Ultimately, we hope this can lead to a new treatment platform that can improve treatment efficacy and reduce side effects in difficult-to-treat diseases, especially cancer.”
The research was mainly funded by the Swedish Cancer Society, the Swedish Research Council, the European Research Council (ERC) and CIMED. Several of the authors have a financial interest in Evox Therapeutics.

Two newly discovered mechanisms in bacteria have been identified that can contribute to the development of antibiotic resistance. Changing the number of copies of resistance genes in bacteria increases antibiotic resistance, and can do so very quickly. According to a new study from Uppsala University published in Nature Communications, these two mechanisms, along with a third known mechanism, can occur independently of each other, even within the same bacterial cell.
The researchers studied heteroresistance, a phenomenon in which the majority of bacteria in a population are sensitive to antibiotics but a very small subpopulation of bacteria exhibits increased antibiotic resistance. Typically, this involves very small numbers of resistant bacteria (around 1 in 100,000) that can continue to grow despite antibiotic treatment. Heteroresistance is a common and concerning phenomenon, as it is difficult to treat and risks accelerating the development of antibiotic-resistant bacteria, complicating antibiotic treatment for patients.
“It was completely unknown until now that these mechanisms could promote heteroresistance. Our study shows that they can accelerate the selection and growth of resistant bacteria during antibiotic treatment. This study, which partly involved animals, makes it more relevant to understanding these processes in humans,” says Helen Wang, the last author of the study.
Bacteria can spread resistance genes to each other through plasmids. Plasmids are small free-standing DNA rings in which bacteria frequently store some of their genes outside the chromosome. In this study, researchers revealed two new mechanisms involving plasmids, in which the number of copies of plasmids carrying resistance genes can increase up to 90 times. The study demonstrates that these two mechanisms and a third known mechanism involving gene amplification, can operate in parallel in the same bacterial cell.
“Heteroresistance involving an increased number of copies of resistance genes is much more complex than previously thought. Bacteria can actually use three different mechanisms, all of which can occur in parallel in the same bacterium, to temporarily increase the number of copies of resistance genes and thereby generate antibiotic resistance,” says Hervé Nicoloff, the study’s first author.
“All three mechanisms are unstable and can quickly revert to sensitivity in the absence of antibiotics. This makes it more difficult to detect the resistant bacteria during a clinical examination, as they disappear so quickly. Given what we now know, it is important to be able to develop better diagnostic methods that can detect increased antibiotic resistance,” adds Helen Wang.

For many patients with a deadly type of brain cancer called glioblastoma, chemotherapy resistance is a big problem.
Current standard treatments, including surgery, radiation, and chemotherapy using the drug temozolomide, have limited effectiveness and have not significantly changed in the past five decades. Although temozolomide can initially slow tumor progression in some patients, typically the tumor cells rapidly become resistant to the drug.
But now, Virginia Tech researchers with the Fralin Biomedical Research Institute at VTC may have moved a step closer to a solution.
Working with glioblastoma cell cultures, including glioblastoma stem cells derived from patient specimens, and laboratory mouse models harboring human cancer cells, scientists have pinpointed an effective molecular signaling pathway that is thought to be crucial for cancer cell survival during temozolomide treatment. The findings are now online in iScience, an open-access journal of Cell Publishing.
“In the past 50 years, treatment options for glioblastoma have remained largely unchanged, relying on surgery, radiation, and temozolomide,” said Zhi Sheng, senior author of the study and assistant professor at the Fralin Biomedical Research Institute. “However, temozolomide’s effectiveness is limited, and resistance to the chemotherapy inevitably develops in patients. Since it’s the only currently available approved chemotherapy that can effectively reach the brain, finding ways to restore its effectiveness is crucial in addressing the treatment failure in glioblastoma.”
Researchers examined the Phosphoinositide 3 Kinase (PI3K) molecular signaling pathway, which is like a communication system inside cells. It tells cells how to grow, survive, and divide. When this pathway is activated, it can promote cancer growth, so scientists and clinicians generally thought blocking it could be a way to treat cancer.
Their results have not been successful.

In the new research, Fralin Biomedical Research Institute scientists found that in some brain cancer patients who didn’t respond to treatment, levels were high of a specific form of the signaling protein called PI3K-beta that helps regulate cellular processes.
When they blocked just PI3K-beta in cell cultures and mouse models harboring cancer cells, the tumor cells became more sensitive to temozolomide treatment. In addition, using a drug that blocks PI3K-beta along with the usual treatment slowed down the cancer cells’ growth.
Researchers are uncertain why PI3K, in its various forms, are very similar in structure yet do different things in the body.
“The reason previous treatments targeting the PI3K pathway failed is because they didn’t distinguish between PI3K-beta and its related proteins,” Sheng said. “This research shows that PI3K-beta is specific to glioblastoma, making it the crucial target for effective treatment.”
Going forward, overcoming the blood-brain barrier remains a hurdle for delivering P13K-beta inhibitors into the brain, which will be crucial for translating the findings into the clinic to help patients.
“We will resolve these issues in our future studies,” Sheng said.
Co-first authors of the study are Kevin Pridham, a former postdoctoral associate at the Fralin Biomedical Research Institute, and Kasen Hutchings and Patrick Beck, two former medical students at the Virginia Tech Carilion School of Medicine who are pursuing their medical careers in radiology in Las Vegas and pediatrics in Philadelphia, respectively.
Cell specimens were provided by Carilion Clinic. Study results are in part based on data generated by The Cancer Genome Atlas Research Network, the Dependency Map, the Genotype-Tissue Expression, or the Chinese Glioma Genome Atlas. The research was supported by the National Institutes of Health.

As research continues to produce evidence about the underlying causes of obesity and optimal strategies to treat and manage obesity have evolved, there are disparities in application of the latest scientific advances in the clinical care that people with obesity receive. Widespread adoption of current findings, consistency of care and expertise in obesity care varies by health care professional and institution. These findings are detailed in a new American Heart Association scientific statement, “Implementation of Obesity Science Into Clinical Practice,” published today in the Association’s flagship scientific journal Circulation.
“Obesity is undeniably a critical public health concern in the U.S. and around the world, affecting nearly all populations and straining our health care systems,” said Deepika Laddu, Ph.D., FAHA, chair of the statement writing committee and a senior research scientist at Arbor Research Collaborative for Health in Ann Arbor, Michigan. “As a major risk factor for heart disease, obesity has significantly hindered progress in reducing heart disease rates. Despite advancements in understanding the complexities of obesity and newer treatment options, major gaps remain between obesity research and real-world implementation in clinical practice.”
Studies show intensive lifestyle therapy is considerably more effective for weight loss than brief advice from a health care professional. However, general educational information is offered more frequently by health professionals rather than referrals to classes, programs or tangible resources for lifestyle changes. One study revealed that only 16% of health care professionals had working knowledge about evidence-based lifestyle treatments for obesity, including diet and nutrition, physical activity and intensive behavioral therapy referral. Other barriers to addressing weight loss are exacerbated by socioeconomic and racial or ethnic inequities. People of diverse races and ethnicities and people who are covered by Medicare or Medicaid are less likely to be referred to weight management programs or to have them covered by insurance.
The number of people living with obesity is increasing worldwide. For about 30 years, the prevalence of obesity in the United States and around the world has been escalating. Recent estimates indicate more than 40% of U.S. adults ages 20 and older are living with obesity, according to the U.S. Centers for Disease Control and Prevention.
Research has led experts to unlock the multifactorial causes of obesity, including sociological and physiological determinants of health. Treatments for obesity have also evolved with more strategies for lifestyle modifications, medication therapy and bariatric (weight-loss) surgery. However, each treatment approach comes with challenges.
“While significant strides have been made in advancing the science to help us understand obesity, there remains a considerable gap between what we know and what happens in the doctor’s office,” said Laddu. “Health care professionals and health care systems need to find better ways to put what we know about obesity into action so more people can get the right support and treatment. Adopting new technologies and telemedicine, making referrals to community-based weight management programs to encourage behavioral change, providing social support and increasing reach and access to treatments are just some of the promising methods we could implement to unlock successful, evidence-based obesity care.”
Weight loss medications
Glucagon-like peptide-1 (GLP-1) agonists, such as high-dose semaglutide and tirzepatide, are the most recently FDA-approved medications for long-term weight management, and both are associated with an average weight loss of more than 10% at six months in clinical studies. However, despite half of adults in the U.S. meeting the BMI criteria for obesity and being eligible for these medications, a small proportion of this population is currently taking them. Until recently, the primary barriers to greater use of anti-obesity medications were lack of insurance coverage and high out-of-pocket costs for these medications.

Since the beginning of the Medicare (Part D) program in 2006, all medications taken for weight loss have been excluded from basic coverage. In March, the Centers for Medicare and Medicaid Services (CMS) determined that Medicare and Medicaid can cover the anti-obesity medication semaglutide when it is approved by the FDA for an additional use. That decision included high-dose semaglutide, which is FDA-approved for weight loss and to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and either obesity or overweight. State Medicaid programs, which provide health care coverage for people in low-income populations and who are disproportionately affected by obesity and heart disease, are required to cover nearly all FDA-approved anti-obesity medications for people meeting the health and body mass index (BMI) criteria. However, state health plans may require step therapy with other treatments or medications prior to approving use of GLP-1 medications.
“FDA approval and insurance coverage of the latest treatments, including GLP-1 medications, are integral to improving access to care and outcomes for people who need these therapies the most. This is especially true for high-risk, high-need patients for the prevention of adverse cardiovascular events. It is encouraging that these steps in increasing access may lead to reduced risk of CVD and improved outcomes for potentially millions of adults in the U.S.,” said the scientific statement’s Vice Chair Ian J. Neeland, M.D., FAHA, director of cardiovascular prevention, director of the Center for Integrated and Novel Approaches in Vascular-Metabolic Disease at University Hospitals Harrington Heart and Vascular Institute at Institute, and an associate professor of medicine at the Case Center for Diabetes, Obesity and Metabolism at Case Western Reserve University School of Medicine, both in Cleveland.
Weight loss surgery
In the decades since bariatric (weight loss) surgery was first introduced as an option for people with severe obesity, there have been advances in the expertise and safety of the procedures, as well as an increased understanding of the health benefits that often result after bariatric surgery. A comprehensive review of studies focused on weight loss surgeries showed that patients who underwent bariatric surgery had lower risks of cardiovascular disease and decreased risks for multiple other obesity-associated conditions, including Type 2 diabetes and high blood pressure. One challenge facing health care professionals is ensuring that the populations with the greatest needs have access to bariatric surgery in terms of costs, resources and social support.
The statement describes strategies that both address these challenges and improve how obesity-based research is incorporated into clinical care. The statement also identifies the need to develop solutions across populations in order to manage obesity at the community level. Potential improved public health policies and future research to expand patient care models and optimize the delivery and sustainability of equitable obesity-related care are suggested.
Specific approaches are highlighted in the statement to help bridge the gap between the science about obesity and clinical care, such as: To reach and successfully impact populations in need, health care professionals may consider how social determinants of health, including insurance type, household income, race and ethnicity, environment, health literacy, access to health-promoting resources and social supports all influence the likelihood of successful patient treatment. Education for health care professionals explaining the complex origins and clinical consequences of obesity is discussed. Such training should emphasize information about diagnosis, prevention and treatment of obesity. Despite the high prevalence of obesity around the world, there is a lack of education programs centered on obesity for medical professionals. Further evaluation of health policy changes that health care systems and insurance plans can implement and scale in order to make obesity treatment affordable for patients, especially those at high risk for adverse outcomes such as cardiovascular disease. A framework for delivering obesity care into clinical practice settings is reviewed, as well as efforts by some professional societies for developing interventions that make obesity treatment more accessible.”The statement emphasizes the importance of a comprehensive approach across different levels of health care delivery and public policy, along with the adoption of feasible, evidence-based strategies in clinical settings,” said Laddu. “It also underscores the need for future research and policy changes to improve current patient care models and ensure equitable access to obesity-related care for people in underrepresented groups.”

The scientific statement also provides possible solutions for how to help people in their day-to-day lives, including interventions with digital technology and access through telemedicine. However, more research is needed in obesity science and treatment. Limited understanding of the cost-effectiveness of obesity prevention and the long-term health outcomes for established therapies has hindered the implementation of obesity science into clinical settings. Cross-collaborative obesity science research between stakeholders and health economists may serve as the bridge to developing and scaling cost-effective prevention programs.
Further research into Food Is Medicine approaches in health care, such as medically tailored meals and produce prescriptions, to prevent and treat cardiovascular disease and other diet-related diseases are also being explored in several settings including the Association’s Health Care by FoodTM initiative.
This scientific statement was prepared by the volunteer writing group on behalf of the American Heart Association Obesity Committee of the Council On Lifestyle and Cardiometabolic Health; the Council on Epidemiology and Prevention; the Council on Clinical Cardiology, the Council on Hypertension; the Council on the Kidney in Cardiovascular Disease; and the Council on Cardiovascular and Stroke Nursing. American Heart Association scientific statements promote greater awareness about cardiovascular diseases and stroke issues and help facilitate informed health care decisions. Scientific statements outline what is currently known about a topic and what areas need additional research. While scientific statements inform the development of guidelines, they do not make treatment recommendations. American Heart Association guidelines provide the Association’s official clinical practice recommendations.
Additional co-authors and members of the writing group are Mercedes Carnethon, Ph.D., FAHA; Fatima C. Stanford, M.D., M.P.H., M.P.A., M.B.A., FAHA; Morgana Mongraw-Chaffin, Ph.D., FAHA; Bethany Barone Gibbs, Ph.D., FAHA; Chiadi E. Ndumele, M.D., Ph.D., FAHA; Chris T. Longenecker, M.D., FAHA; Misook L. Chung, Ph.D., R.N., FAHA; and Goutham Rao, M.D. 

In a pioneering achievement, a research team led by experts at Cincinnati Children’s have developed the world’s first human mini-brain that incorporates a fully functional blood-brain barrier (BBB).
This major advance, published May 15, 2024, in Cell Stem Cell, promises to accelerate the understanding and improved treatment of a wide range of brain disorders, including stroke, cerebral vascular disorders, brain cancer, Alzheimer’s disease, Huntington disease, Parkinson’s disease, and other neurodegenerative conditions.
“Lack of an authentic human BBB model has been a major hurdle in studying neurological diseases,” says lead corresponding author Ziyuan Guo, PhD, “Our breakthrough involves the generation of human BBB organoids from human pluripotent stem cells, mimicking human neurovascular development to produce a faithful representation of the barrier in growing, functioning brain tissue. This is an important advance because animal models we currently use in research do not accurately reflect human brain development and BBB functionality.”
What is the blood-brain barrier?
Unlike the rest of our bodies, blood vessels in the brain feature an extra lining of tightly packed cells that sharply limit the size of molecules that can pass from the bloodstream into the central nervous system (CNS).
A properly functioning barrier maintains brain health by preventing the entry of harmful substances while allowing essential nutrients to reach the brain. However, that same barrier also prevents many potentially helpful medicines from reaching the brain. Also, several neurological disorders are caused, or worsened, when the blood-brain barrier forms improperly or begins breaking down.
Significant differences between human and animal brains have resulted in many hopeful new drugs that were developed relying heavily on animal models to fail later when tested in human study participants.

“Now, through stem cell bioengineering, we have developed an innovative platform based on human stem cells that allows us to study the intricate mechanisms governing BBB function and dysfunction. This provides unprecedented opportunities for drug discovery and therapeutic intervention,” Guo says.
Overcoming a long-running challenge
Research teams worldwide have been racing to develop brain organoids — tiny, growing 3D structures that mimic the early steps of brain formation. Unlike cell types grown flat in a lab dish, organoid cells are connected. They self-assemble into spherical forms. Their cells “talk” to each other like human cells normally do during fetal development.
Cincinnati Children’s has been a leader in developing other types of organoids, including the world’s first functional intestine, stomach and esophagus organoids. But until now, no research center had succeeded at making a brain organoid that features the special barrier lining found in human brain blood vessels.
The research team calls their new model “BBB assembloids.” Their name reflects the advance that made the breakthrough possible. These assembloids combine two distinct types of organoids: brain organoids that replicate human brain tissue and blood vessel organoids that mimic vascular structures.
The combination process began with brain organoids measuring 3 to 4 millimeters in diameter and blood vessel organoids about 1 millimeter in diameter. Over the course of about a month, these separate structures fused into a single sphere measuring slightly more than 4 millimeters in diameter (about 1/8 of an inch, or roughly the size of a sesame seed).

These integrated organoids recreate many of the complex neurovascular interactions observed in the human brain, but they are not complete models of the brain. For example, the tissue does not contain immune cells and there are no connections to the rest of the body’s nervous system.
Research teams at Cincinnati Children’s have shown other successes at merging and layering organoids from different cell types to form more complex “next generation” organoids. Those successes helped inform the new brain organoid work.
Importantly, the BBB assembloids can be grown using neurotypical human stem cells or stem cells from people with specific brain diseases, thus reflecting gene variants and other conditions that can lead to a malfunctioning blood-brain barrier.
Initial proof of concept
To demonstrate the potential utility of the new assembloids, the researcher team used a line of patient-derived stem cells to make assembloids that accurately replicated key features of a rare brain condition called a cerebral cavernous malformation.
This genetic disorder, which is characterized by dysfunctional blood-brain barrier integrity, results in clusters of abnormal blood vessels in the brain that often resemble raspberries in their appearance. The disorder significantly increases risk of stroke.
“Our model accurately recapitulated the disease phenotype, offering new insights into the underlying molecular and cellular pathology of cerebral vascular disorders,” Guo says.
Potential applications
The co-authors envision a variety of potential uses of BBB assembloids: Personalized Drug Screening: Patient-derived BBB assembloids could serve as avatars to tailor therapies for patients based on their unique genetic and molecular profiles. Disease Modeling: A number of neurovascular disorders, including rare and genetically complex conditions, lack good model systems for research. Success at making BBB assembloids could accelerate development of human brain tissue models for more conditions. High-Throughput Drug Discovery: Scaling up assembloid production could allow more accurate, and more rapid analysis of whether potential brain medications can effectively cross the BBB. Environmental Toxin Testing: Often based heavily on animal model systems, BBB assembloids could help evaluate the toxic effects of environmental pollutants, pharmaceuticals, and other chemical compounds. Immunotherapy Development: Through investigating the role of the BBB in neuroinflammatory and neurodegenerative diseases, the new assembloids could support delivering immune-based therapies to the brain. Bioengineering and Biomaterials Research: Biomedical engineers and materials scientists will likely benefit from having a lab model of the BBB to test novel biomaterials, drug delivery vehicles, and tissue engineering strategies.”Overall, BBB assembloids represent a game-changing technology with broad implications for neuroscience, drug discovery, and personalized medicine,” Guo says.
About the study
In addition to Guo, the co-first authors of the study were: Lan Dao, MS, and Lu Lu, PhD, from Cincinnati Children’s; Tianyang Xu from UC San Diego; and Zhen You from the Mayo Clinic. Co-corresponding authors were Sheng Zhong, PhD, from UC San Diego and L. Frank Huang, PhD, from the Mayo Clinic.
Co-authors from Cincinnati Children’s also included Avijite Kumer Sarkar, PhD, Hui Zhu, PhD, George Yoshida, BA, Yifei Miao, PhD, Sarah Mierke, MD, Srijan Kalva, Mingxia Gu, MD, PhD, and Sudhakar Vadivelu, MD. The Single Cell Genomics Facility at Cincinnati Children’s and the NIH NeuroBioBank also provided key support to the research.
Guo and Dao have a pending patent application (“Vascularized brain organoids having a CCM-like feature and methods of making and use,” U.S. Application no. 63/510,463) related to this research. Zhong is a founder of Genemo, Inc.

A new advanced artificial intelligence (AI) algorithm may lead to better — and earlier — predictions and novel therapies for autoimmune diseases, which involve the immune system mistakenly attacking their body’s own healthy cells and tissues. The algorithm digs into the genetic code underlying the conditions to more accurately model how genes associated with specific autoimmune diseases are expressed and regulated and to identify additional genes of risk.
The work, developed by a team led by Penn State College of Medicine researchers, outperforms existing methodologies and identified 26% more novel gene and trait associations, the researchers said. They published their work today (May 20) in Nature Communications.
“We all carry some DNA mutations, and we need to figure out how any one of these mutations may influence gene expression linked to disease so we can predict disease risk early. This is especially important for autoimmune disease,” said Dajiang Liu, distinguished professor, vice chair for research, and director of artificial intelligence and biomedical informatics at the Penn State College of Medicine and co-senior author of the study. “If an AI algorithm can more accurately predict disease risk, it means we can carry out interventions earlier.”
Genetics often underpin disease development. Variations in DNA can influence gene expression, or the process by which the information in DNA is converted into functional products like a protein. How much or how little a gene is expressed can influence disease risk.
Genome-wide association studies (GWAS), a popular approach in human genetics research, can home in on regions of the genome associated with a particular disease or trait but can’t pinpoint the specific genes that affect disease risks. It’s like sharing your location with a friend with the precise location setting turned off on your smartphone — the city might be obvious, but the address is obscured. Existing methods are also limited in the granularity of its analysis. Gene expression can be specific to certain types of cells. If the analysis doesn’t distinguish between distinct cell types, the results may overlook real causal relationships between genetic variants and gene expression.
The research team’s method, dubbed EXPRESSO for EXpression PREdiction with Summary Statistics Only, applies a more advanced artificial intelligence algorithm and analyzes data from single-cell expression quantitative trait loci, a type of data that links genetic variants to the genes they regulate. It also integrates 3D genomic data and epigenetics — which measures how genes may be modified by environment to influence disease — into its modeling. The team applied EXPRESSO to GWAS datasets for 14 autoimmune diseases, including lupus, Crohn’s disease, ulcerative colitis and rheumatoid arthritis.
“With this new method, we were able to identify many more risk genes for autoimmune disease that actually have cell-type specific effects, meaning that they only have effects in a particular cell type and not others,” said Bibo Jiang, assistant professor at the Penn State College of Medicine and senior author of the study.

The team then used this information to identify potential therapeutics for autoimmune disease. Currently, there aren’t good long-term treatment options, they said.
“Most treatments are designed to mitigate symptoms, not cure the disease. It’s a dilemma knowing that autoimmune disease needs long-term treatment, but the existing treatments often have such bad side effects that they can’t be used for long. Yet, genomics and AI offer a promising route to develop novel therapeutics,” said Laura Carrel, professor of biochemistry and molecular biology at the Penn State College of Medicine and co-senior author of the study.
The team’s work pointed to drug compounds that could reverse gene expression in cell types associated with an autoimmune disease, such as vitamin K for ulcerative colitis and metformin, which is typically prescribed for type 2 diabetes, for type 1 diabetes. These drugs, already approved by the Food and Drug Administration as safe and effective for treating other diseases, could potentially be repurposed.
The research team is working with collaborators to validate their findings in a laboratory setting and, ultimately, in clinical trials.
Lida Wang, a doctoral student in the biostatistics program, and Chachrit Khunsriraksakul, who earned a doctorate in bioinformatics and geonomics in 2022 and his medical degree in May from Penn State, co-led the study. Other Penn State College of Medicine authors on the paper include: Havell Markus, who is pursuing a doctorate and a medical degree; Dieyi Chen, doctoral candidate; Fan Zhang, graduate student; and Fang Chen, postdoctoral scholar. Xiaowei Zhan, associate professor at UT Southwestern Medical Center, also contributed to the paper.
Funding from the National Institutes of Health (grant numbers R01HG011035, R01AI174108 and R01ES036042) and the Artificial Intelligence and Biomedical Informatics pilot grant from the Penn State College of Medicine supported this work.

Contrary to expectation, a major study found that weed use among minors was lower in states where the drug was legal.With weed these days, it’s a Willy Wonka world: chocolate bars, lollipops, exotic-flavored gummies — to say nothing of joints, vapes, drinks and the rest. Twenty-four states and the District of Columbia have now legalized the sale of marijuana for recreational use, prompting innovation, lowering prices and making the drug — more potent than ever — more widely available. The Biden administration this week recommended easing the federal regulations on cannabis.What does all of this mean for adolescents?Studies have demonstrated that marijuana use can harm the developing brain. Some new strains have been linked to psychosis. Many health experts have worried that relaxing the laws around cannabis will lead to more use of the drug among minors. But Rebekah Levine Coley, a developmental psychologist at Boston College, is less certain.In April, she and colleagues published a study in JAMA that examined drug use patterns among 900,000 high school students from 2011 to 2021, using self-reported data from the Youth Risk Behavior Survey. They found that fewer minors reported having used cannabis in the previous month in states where the drug had been legalized. But they also found that in the 18 states that had both legalized cannabis and allowed retail sales of the drug, some adolescents who were users of the drug used it more frequently. The net effect was a flat or slight decline in cannabis use among adolescents.Dr. Coley spoke to The New York Times about the study, and its implications for state and federal drug policy. This conversation has been edited and condensed for clarity.It seems sensible to assume that legalizing marijuana would lead to more use by young people.Yes, common sense might argue that as cannabis becomes legalized, it will be more accessible. There will be fewer potential legal repercussions, hence availability would increase and use would increase.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Contrary to expectation, a major study found that weed use among minors was lower in states where the drug was legal.With weed these days, it’s a Willy Wonka world: chocolate bars, lollipops, exotic-flavored gummies — to say nothing of joints, vapes, drinks and the rest. Twenty-four states and the District of Columbia have now legalized the sale of marijuana for recreational use, prompting innovation, lowering prices and making the drug — more potent than ever — more widely available. The Biden administration this week recommended easing the federal regulations on cannabis.What does all of this mean for adolescents?Studies have demonstrated that marijuana use can harm the developing brain. Some new strains have been linked to psychosis. Many health experts have worried that relaxing the laws around cannabis will lead to more use of the drug among minors. But Rebekah Levine Coley, a developmental psychologist at Boston College, is less certain.In April, she and colleagues published a study in JAMA that examined drug use patterns among 900,000 high school students from 2011 to 2021, using self-reported data from the Youth Risk Behavior Survey. They found that fewer minors reported having used cannabis in the previous month in states where the drug had been legalized. But they also found that in the 18 states that had both legalized cannabis and allowed retail sales of the drug, some adolescents who were users of the drug used it more frequently. The net effect was a flat or slight decline in cannabis use among adolescents.Dr. Coley spoke to The New York Times about the study, and its implications for state and federal drug policy. This conversation has been edited and condensed for clarity.It seems sensible to assume that legalizing marijuana would lead to more use by young people.Yes, common sense might argue that as cannabis becomes legalized, it will be more accessible. There will be fewer potential legal repercussions, hence availability would increase and use would increase.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

In Canada, cannabis poisonings rose sharply among people 65 and older after the country legalized the drug, a new study found.The NewsAs more places legalize marijuana, policymakers and health officials have worried about the health risks that the drug may pose to adolescents. But a new study suggests that an additional demographic is at risk: seniors.The study, published Monday in JAMA Internal Medicine, found that after Canada legalized marijuana, the number of emergency room visits for cannabis poisoning rose sharply among people ages 65 and older. Poisonings doubled after Canada legalized sale of the cannabis flower, and then tripled just 15 months later, when Canada legalized the sale of edibles.“It’s often a baked good, a chocolate or a gummy,” said Dr. Nathan Stall, a geriatrician at Mount Sinai Hospital and researcher at Women’s College Hospital in Toronto, and lead author on the study. Dr. Stall noted that researchers and emergency room doctors were finding that seniors used drugs intentionally but also sometimes by accident, when edibles were mistaken for regular food or snacks.Symptoms of cannabis poisoning can include dizziness, confusion, nausea, loss of coordination and balance, drowsiness and hallucinations.The findings were consistent with other research published in the United States, Dr. Stall said, and showed that more attention needed to be paid to drug use by seniors, and to the health effects.“It’s somewhat in the shadows, and there is some ageism and bias in thinking that older adults aren’t using drugs,” Dr. Stall said.Edible marijuana samples at a cannabis testing laboratory in Santa Ana, Calif.Chris Carlson/Associated PressThe StudyThe study looked at 2,322 emergency room visits for cannabis poisoning among people 65 and older in Ontario. The visits spanned 2015 through 2022, allowing researchers to see what happened before and after October 2018, when Canada legalized the sale of dried cannabis, and January 2020, when the sale of edibles was legalized.In 2015, there were 55 emergency room visits caused by cannabis poisoning. That figure rose steadily to 462 by 2021, and then fell off slightly to 404 in 2022.Dr. Stall said he was motivated to undertake the study after being called into the emergency room to consult on an octogenarian who was experiencing severe confusion. The patient was barely conscious and showed strokelike symptoms. Multiple tests revealed no clear cause, until Dr. Stall ordered a toxicology test and found cannabis in the patient’s urine.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

It’s one of the most common psychiatric disorders in adults. Yet there are no U.S. guidelines for diagnosing and treating patients beyond childhood.Just before Katie Marsh dropped out of college, she began to worry that she might have attention deficit hyperactivity disorder.“Boredom was like a burning sensation inside of me,” said Ms. Marsh, who is now 30 and lives in Portland, Ore. “I barely went to class. And when I did, I felt like I had a lot of pent-up energy. Like I had to just move around all the time.”So she asked for an A.D.H.D. evaluation — but the results, she was surprised to learn, were inconclusive. She never did return to school. And only after seeking help again four years later was she diagnosed by an A.D.H.D. specialist.“It was pretty frustrating,” she said.A.D.H.D. is one of the most common psychiatric disorders in adults. Yet many health care providers have uneven training on how to evaluate it, and there are no U.S. clinical practice guidelines for diagnosing and treating patients beyond childhood.Without clear rules, some providers, while well-intentioned, are just “making it up as they go along,” said Dr. David W. Goodman, an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.This lack of clarity leaves providers and adult patients in a bind.“We desperately need something to help guide the field,” said Dr. Wendi Waits, a psychiatrist with Talkiatry, an online mental health company. “When everyone’s practicing somewhat differently, it makes it hard to know how best to approach it.”We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.