Experiencing puberty earlier, compared to same-age peers, may be one of the mechanisms through which childhood risk factors influence adult cardiometabolic health issues, according to a study published March 27, 2024 in the open-access journal PLOS ONE by Maria Bleil from the University of Washington, USA and colleagues.
Adverse experiences in childhood are frequently linked to poor health in adulthood. Most of the conceptual models describing adversity-related changes that may be adaptive to stress in the short-term but are risky to long-term health don’t specifically include puberty, which links childhood and adulthood and is itself also sensitive to the child’s environment. Earlier onset of puberty is often linked to factors like race (with Black and Latina girls developing earlier than White girls), mother’s age at her first period, infant weight gain and childhood obesity, and adverse experiences like childhood socioeconomic disadvantage, stressful parent-child relationships, and other stressful life events.
Here, Bleil and colleagues modeled pubertal timing and health risks in a cohort of women who had participated in the 30-year NICHD Study of Early Child Care and Youth Development prospective study of children and their families. Participants were followed from birth to adolescence (1991-2009) to examine trajectories of child health and development, with an additional in-person study follow-up (2018-2022) among participants ages 26 to 31 to capture social, behavioral, and health status information in adulthood. The authors fit models to data from the full sample of 655 women.
The authors found that later pubertal onset (later breast development, pubic hair onset, and first period) predicted lower adulthood cardiometabolic risk. These puberty indicators were also found to mediate the effects of factors like mother’s age at her first period, race, BMI percentile, and childhood socioeconomic status on adult cardiometabolic risk.
It’s important to note that this study maps predictive relationships between childhood risk factors, timing of puberty, and adulthood cardiometabolic risks, but cannot prove causation. That said, the pattern of results provides strong longitudinal evidence for the role of puberty onset as a pathway linking early life exposures and adulthood cardiometabolic health — and suggests targeting puberty onset may improve health more broadly in at-risk girls. The authors hope future studies will both replicate their findings and better characterize the nature of the links identified here.
The authors add: “This study suggests the timing of pubertal development in girls is an important pathway through which early life risk factors, such as prepubertal body mass index and socioeconomic position, influence cardiometabolic health in adulthood. The implications of this work are that pubertal development and its timing should be considered, and potentially targeted, in efforts to improve cardiometabolic health.”

A pair of medications that make malignant cells act as if they have a virus could hold new promise for treating colorectal cancers and other solid tumors, reports a study published today in Science Advances.
The preclinical research, led by Van Andel Institute scientists, determined how low doses of a DNMT inhibitor sensitize cancer cells to an EZH2 inhibitor, resulting in a one-two punch that combats cancer cells better than either drug alone.
The findings are the foundation for an upcoming Phase I clinical trial to evaluate this combination in people with colorectal cancer or other solid tumors.
“DNMT inhibitors are approved to treat blood cancer while EZH2 inhibitors are approved to treat blood cancer and a rare type of sarcoma. To date, they’ve had limited individual success in solid tumors like colorectal cancer,” said Van Andel Institute Professor Scott Rothbart, Ph.D., the study’s corresponding author. “Our findings highlight the promise of combination cancer therapies by revealing how these two medications interact, with the DNMT inhibitor priming cancer cells in a way that makes the EZH2 inhibitor more effective.”
DNMT and EZH2 inhibitors work by controlling the epigenetic processes that regulate gene expression. In cancer, epigenetic errors enable malignant cells to survive and proliferate — and offer critical targets for treatment.
Previous studies show that DNMT inhibitors cause cancer cells to behave as if infected by a virus, which makes the cells more susceptible to attack by one’s own immune system. In their new study, Rothbart and colleagues demonstrated that combining DNMT and EZH2 inhibitors activate this viral mimicry process more effectively than either drug on its own. The upcoming trial will be the first time these two medication types will be combined to enhance the activities of these inhibitors in solid tumors.
Colorectal cancers are the second leading cause of cancer death globally, according to the World Health Organization. More than 1.9 million cases were diagnosed in 2020, with incidence expected to rise to 3.2 million cases by 2040. Although screening and early detection have driven down colorectal cancer rates among older people in the U.S., rates are rising in younger people.

“Although it is not clear why colorectal cancer cases are rising among young people, it is clear that we need more effective treatment strategies,” Rothbart said. “Combining medications may be a powerful way to simultaneously target multiple drivers of cancer. In addition to revealing how DNMT and EZH2 inhibitors work together, our findings suggest that epigenetic drugs also may sensitize tumors to immunotherapy, which offers another important opportunity to enhance cancer treatment.”
The upcoming trial will be supported by the Van Andel Institute-Stand Up To Cancer© (SU2C) Epigenetics Dream Team, a multi-institutional collaboration that evaluates promising potential combination therapies for cancer, and a National Cancer Institute Specialized Programs of Research Excellence (SPORE) award, a prestigious five-year grant that supports a team of scientists seeking to improve epigenetic cancer therapies.
Today’s findings were made possible in part by a SPORE-supported subproject on DNMT and EZH2 inhibitors led by Rothbart and Stephen Baylin, M.D., of Johns Hopkins University and Van Andel Institute. Baylin also serves as co-leader of the VAI-SU2C Epigenetics Dream Team and is an author on today’s study.
The study’s first authors are Alison A. Chomiak, Ph.D., and Rochelle L. Tiedemann, Ph.D., of VAI. Other authors include Yanqing Liu, M.D., Ashley K. Wiseman, M.S., and Kate E. Thurlow, M.Sc., of VAI; Xiangqian Kong, Ph.D., Ying Cui, Ph.D., and Michael E. Topper, Ph.D., of Johns Hopkins University; and Evan M. Cornett, Ph.D., of Indiana University.

A global shift to a healthier, more sustainable diet could be a huge lever to limit global warming to 1.5°C, researchers at the Potsdam Institute for Climate Impact Research (PIK) find. The resulting reduction of greenhouse gas emissions would increase the available carbon budget compatible with limiting global warming to 1.5°C, and allow to achieve the same climate outcome with less carbon dioxide removal and less stringent CO2 emissions reductions in the energy system. This would also reduce emission prices, energy prices and food expenditures.
“We find that a more sustainable, flexitarian diet increases the feasibility of the Paris Agreement climate goals in different ways,” says Florian Humpenöder, PIK scientist and co-lead author of the study to be published in Science Advances. “The reduction of greenhouse gas emissions related to dietary shifts, especially methane from ruminant animals raised for their meat and milk, would allow us to extend our current global CO2 budget of 500 gigatons by 125 gigatons and still stay within the limits of 1.5°C with a 50 percent chance,” he adds.
Putting a price on greenhouse gas (GHG) emissions in the energy and land system is an important policy instrument to stay within the limits of 1.5°C warming. “Our results show that compared to continued dietary trends, a more sustainable diet not only reduces impacts from food production within the land system, such as deforestation and nitrogen losses. It also reduces GHG emissions from the land system to such an extent that it cuts economy-wide 1.5°C-compatible GHG prices in 2050 by 43 percent,” explains co-lead author Alexander Popp, leader of the working group land-use management at PIK. “Moreover, healthy diets would also reduce our dependency on carbon dioxide removal in 2050 by 39 percent,” he adds.
Flexitarian diet could make a marked difference for the feasibility of the 1.5°C target
Up to now, existing literature did not allow to single-out the contribution of dietary shifts alone for the feasibility of the 1.5°C limit. In the new study, PIK scientists investigated how dietary shifts would contribute towards the feasibility of 1.5°C transformation pathways relative to a scenario without dietary shifts. The researchers used the open-source Integrated Assessment Modelling framework REMIND-MAgPIE to simulate 1.5°C pathways, one including dietary shifts towards the EAT-Lancet Planetary Health Diet by 2050 in all world regions. “The EAT-Lancet Planetary Health Diet is a flexitarian diet predominantly featuring a wide variety of plant-based foods, a marked reduction of livestock products especially in high- and middle-income regions, and restricted intake of added sugars, among other things,” says co-author Isabelle Weindl from PIK.
However, considerable challenges are yet to be addressed: Decision-making in food policy is often dispersed across different institutions and ministries, which hinders the implementation of coherent policies in support of healthy diets. Moreover, social inclusion and compensation schemes are central for a just transition to healthy diets, the authors state.
“The results indicate that a shift in our diets could make a considerable difference if we do not want to crash through the 1.5°C limit in the next 10 to 15 years. This calls for globally concerted efforts to support the transition towards sustainable healthy diets,” concludes Johan Rockström, PIK director and co-author of the study.

Published18 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Jill LockhartBy Andrew Picken & Lisa SummersBBC Scotland NewsA mum has been told her ten-year-old daughter’s spinal condition is now inoperable after having planned surgery cancelled seven times since September. The curvature of Eva Tennent’s spine is now so severe that her mum Jill Lockhart fears she will not survive. Her family said three of her operations at Edinburgh’s Sick Kids Hospital were postponed due to staff shortagesIt comes as BBC News learned that one of Scotland’s three paediatric spinal surgeons has been suspended. Patients and families under the care of surgeon Chris Adams, who was treating Eva, were told he would no longer be treating them last week – but were not told why by NHS officials. The suspension came a day after Mr Adams met with a BBC journalist and accompanied him on a visit to Eva in hospital, which had been requested by her parents. Shaye Armour, 13, was also under Mr Adams’ care ahead of planned spinal surgery in Edinburgh later this year but the teenager was moved to a hospital in Newcastle on Tuesday for a new surgical assessment. Nursing shortages are delaying spinal operations – surgeonChildren face ‘catastrophic’ wait for NHS treatmentWhen will Scotland’s NHS recover from Covid?BBC News is aware of another case where spinal surgery for a child planned with Mr Adams was postponed at the last minute. NHS Lothian said it does not comment on individual members of staff.Dr Tracey Gillies, the board’s medical director, apologised to patients and families affected by rescheduling operations and said the well documented wider pressures on the NHS was partly to blame. Last year, a BBC Disclosure investigation into Scotland’s NHS revealed claims by Mr Adams that nursing shortages at the Edinburgh Royal Hospital for Children and Young People (RHCYP) were contributing to some children waiting up to three times longer than pre-pandemic for spinal surgery. Mr Adams and other staff members raised concerns within NHS Lothian about the number of operations being cancelled due to staffing shortages.The problem of bed and staff shortages is impacting all areas of Scotland’s NHS with The Royal College of Paediatrics and Child Health warning that the number of children waiting for some services had more than doubled in the past 11 years.’They are telling me it’s too late’Eva suffers from Rett syndrome, a rare genetic disorder that affects brain development, and has advanced scoliosis that causes her spine to twist and curve to the side.The curvature of her spine was 60.89 degrees in May, 2022, went up to 107.9 degrees last year and is now at 110 degrees, according to Jill. Her family say they’ve been told her condition means it is now inoperable.Image source, Jill LockhartJill told BBC News that Eva had been booked for surgery seven times since September last year, but each time it has been cancelled.”She was deemed operable in September, October and November – and they were only cancelled because of bed and nurse shortages,” she said. “They have left it so long, and now they are saying it’s too late. It feels like my daughter’s chances of survival have been sacrificed.”Jill said the most recent surgery cancellations were down to Eva’s deteriorating respiratory health, which she believes is a result of the delay in operating and the curvature of the ten-year-old’s spine putting increased pressure on her internal organs. Eva was due to undergo surgery on 28 March but this operation has also been cancelled.”We were told last week that the operation could go ahead,” Jill added.”Now, we’re being told she’s inoperable and I can’t get a proper explanation from the hospital why this situation has changed so quickly.”If Eva had this operation, she could live for another 15 to 30 years with her condition. Without it, she may die.”‘They have just left him in limbo’Image source, Nicole ArmourShaye Armour, from Greenock, has congenital kyphosis scoliosis, a condition which causes his spine to bend forward.The 13-year-old was being treated at Edinburgh’s RHCYP under the care of Mr Adams as part of a series of planned spinal operations this year. His mum Nicole said she was told by NHS Lothian that Mr Adams, who had been Shaye’s surgeon for nearly a decade, was no longer available to treat her son but she was not able to find out why from the senior official she spoke to. She said: “I asked was it personal reasons and he avoided the question. I asked has he been suspended, has he been sacked? “They said he wasn’t sacked, so I said has he been suspended then and the answer was no comment which I found pretty weird because Shaye was in the middle of getting his surgeries done.”This video can not be playedTo play this video you need to enable JavaScript in your browser.”I’m very upset and angry that they have done this to Shaye. They started something and just stopped mid way through, they have just left him in limbo. He’s left in the unknown, he has all these questions but has no answers.”If they delay things more or if they make the slightest mistake Shaye will end up paralysed from the neck down.”Nicole said Shaye “was devastated” by the news as he was very close to Mr Adams, who she described as a “great man”. ‘Significant pressures’Dr Gillies, the medical director of NHS Lothian, said: “We do not comment on individual members of staff.”If a clinician was not to be at work for any reason, patients and their families would be told if it impacted on their care and their case would be reassigned to another surgeon as soon as possible – particularly if it was time sensitive.”In cases of a specialist service, it can often be necessary to link in with the closest centre to ensure the patient is care for appropriately.”She added: “We do know that rescheduling elective procedures can be very upsetting for our patients and their families. We apologise sincerely to those who have been affected, especially those who have been rescheduled a number of times.”We have been open and honest about the significant pressures being experienced across our entire healthcare system and their negative impact on elective procedures and waiting times.”More on this storyChildren face ‘catastrophic’ wait for NHS treatmentPublished6 days agoNurse shortages are delaying spinal ops – surgeonPublished7 March 2023When will Scotland’s NHS recover from Covid?Published1 MarchAround the BBCBBC One – Disclosure, Is the NHS There for Me-

Rowers in the Oxford-Cambridge Boat Race this weekend have been warned of dangerously high levels of E. coli in the River Thames, the latest sign of England’s polluted waterways.The warning was stern: Do not enter the water. Not because of the tide. Not because of sharks. Because of the sewage.For almost two centuries, rowers from Oxford University have raced their rivals from Cambridge in a contest that typically ends with jubilant members of the victorious crew jumping into the River Thames in celebration.This year they will be staying as dry as possible.After the discovery of elevated levels of E. coli in the river, rowers have been urged to stay out of the water, to cover any open wounds and to wash themselves down at a dedicated cleansing station at the finish.The warning from organizers of the annual competition known as the Boat Race is the most striking symbol of the dire and deteriorating state of Britain’s rivers and coastlines. E. coli, which can be contracted from inadequately treated water supplies, can cause a number of symptoms including diarrhea, stomach cramps and occasionally fever. According to Britain’s health service, a small number of people can also develop hemolytic uraemic syndrome which can sometimes lead to kidney failure and death.In recent years, England’s private water companies have faced fierce criticism for discharging sewerage and untreated rainwater into waterways and onto beaches when rainfall is heavy — a tactic they use to prevent the system from backing up.The winning crew from Oxford in the 2009 race threw Colin Groshong, their cox, or the person who steers the boat, into the Thames.Tom Hevezi/Associated PressWe 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.

St. Jude Children’s Research Hospital scientists reversed an aggressive cancer, reverting malignant cells towards a more normal state. Rhabdoid tumors are an aggressive cancer which is missing a key tumor suppressor protein. Findings showed that with the missing tumor suppressor, deleting or degrading the quality control protein DCAF5 reversed the cancer cell state. These results suggest a new approach to curing cancer — returning cancerous cells to an earlier, more normal state rather than killing cancer cells with toxic therapies — may be possible. The results were published today in Nature.
“Rather than making a toxic event that kills rhabdoid cancer, we were able to reverse the cancer state by returning the cells toward normal,” said senior author Charles W.M. Roberts, MD, PhD, Executive Vice President and St. Jude Comprehensive Cancer Center director. “This approach would be ideal, especially if this paradigm could also be applied to other cancers.”
“We found a dependency which actually reverses the cancer state,” said first author Sandi Radko-Juettner, PhD, a former St. Jude Graduate School of Biomedical Sciences student, now a Research Program Manager for the Hematological Malignancies Program at St. Jude. “Standard cancer therapies work by causing toxicities that also damage healthy cells in the body. Here, it appears that we’re instead fixing the problem caused by the loss of a tumor suppressor in this rhabdoid cancer.”
Drugging the un-targetable
In many cancers, there is no easily druggable target. Often, these cancers are caused by a missing tumor suppressor protein, so there is nothing to target directly as the protein is missing. Loss of tumor suppressors is much more common than a protein gaining the ability to drive cancer. Consequently, finding a way to intervene therapeutically in these tumors is a high priority. The researchers were looking for a way to treat an aggressive set of cancers caused by the loss of the tumor suppressor protein SMARCB1 when they found a new approach to treatment.
The St. Jude group found a little-studied protein, DCAF5, was essential to rhabdoid tumors missing SMARCB1. Initially, they identified DCAF5 as a target, using the Dependency Map (DepMap) portal, a database of cancer cell lines and the genes critical for their growth. DCAF5 was a top dependency in rhabdoid tumors. After the initial finding, the scientists genetically deleted or chemically degraded DCAF5. The cancer cells reverted to a non-cancerous state, persisting even in a long-term mouse model.
“We saw a spectacular response,” Roberts said. “The tumors melted away.”
Removing quality control to reverse cancer

Normally, SMARCB1 is an essential component of a larger chromatin-regulating complex of proteins called the SWI/SNF complex. Unexpectedly, the study found that in the absence of SMARCB1, DCAF5 recognizes SWI/SNF as abnormal and destroys the complex. When DCAF5 degrades them, the researchers showed that SWI/SNF re-forms and maintains its ability to open chromatin and regulate gene expression. While the SWI/SNF activity level in the absence of SMARCB1 was to a lesser extent than usual, it was nonetheless sufficient to reverse the cancer state fully.
“DCAF5 is doing a quality control check to ensure that these chromatin machines are built well,” Roberts said. “Think of a factory assembling a machine. You need quality checks to examine and find faults and to pull it off the line if it doesn’t meet standards. DCAF5 is doing such quality assessments for the assembly of SWI/SNF complexes, telling the cell to get rid of complexes if SMARCB1 is absent.”
“The mutation of SMARCB1 shuts off gene programs that prevent cancer. By targeting DCAF5, we’re turning those gene programs back on,” Radko-Juettner said. “We’re reversing the cancer state because the cell is becoming more ‘normal’ when these complexes aren’t targeted for destruction by DCAF5.”
Future therapeutic opportunities to reverse cancer
“From a therapeutic perspective, our results are fascinating,” Radko-Juettner said. “DCAF5 is part of a larger family of DCAF proteins that have been shown to be drug targetable. We showed that when DCAF5 is absent, mice had no discernable health effects, so we could potentially target DCAF5. This can kill the cancer cells but shouldn’t affect healthy cells. Targeting DCAF5 thus has the potential to avoid the off-target toxicity of radiation or chemotherapy, making it a promising therapeutic avenue to pursue.”
Beyond DCAF5, the findings could have implications for other cancers driven by the loss of a tumor suppressor.
“We have demonstrated a beautiful proof of principle,” Roberts said. “Myriad types of cancers are caused by tumor suppressor loss. We hope we may have opened the door to thinking about new ways to approach targeting at least some of these by reversing, instead of killing, cancer.”

Just as you can’t make an omelet without breaking eggs, scientists at Albert Einstein College of Medicine have found that you can’t make long-term memories without DNA damage and brain inflammation. Their surprising findings were published online today in the journal Nature.
“Inflammation of brain neurons is usually considered to be a bad thing, since it can lead to neurological problems such as Alzheimer’s and Parkinson’s disease,” said study leader Jelena Radulovic, M.D., Ph.D., professor in the Dominick P. Purpura Department of Neuroscience, professor of psychiatry and behavioral sciences, and the Sylvia and Robert S. Olnick Chair in Neuroscience at Einstein. “But our findings suggest that inflammation in certain neurons in the brain’s hippocampal region is essential for making long-lasting memories.”
The hippocampus has long been known as the brain’s memory center. Dr. Radulovic and her colleagues found that a stimulus sets off a cycle of DNA damage and repair within certain hippocampal neurons that leads to stable memory assemblies — clusters of brain cells that represent our past experiences. Elizabeth Wood, a Ph.D. student, and Ana Cicvaric, a postdoc in the Radulovic lab, were the study’s first authors at Einstein.
From Shocks to Stable Memories
The researchers discovered this memory-forming mechanism by giving mice brief, mild shocks sufficient to form a memory of the shock event (episodic memory). They then analyzed neurons in the hippocampal region and found that genes participating in an important inflammatory signaling pathway had been activated.
“We observed strong activation of genes involved in the Toll-Like Receptor 9 (TLR9) pathway,” said Dr. Radulovic, who is also director of the Psychiatry Research Institute at Montefiore Einstein (PRIME). “This inflammatory pathway is best known for triggering immune responses by detecting small fragments of pathogen DNA. So at first we assumed the TLR9 pathway was activated because the mice had an infection. But looking more closely, we found, to our surprise, that TLR9 was activated only in clusters of hippocampal cells that showed DNA damage.”
Brain activity routinely induces small breaks in DNA that are repaired within minutes. But in this population of hippocampal neurons, the DNA damage appeared to be more substantial and sustained.

Triggering Inflammation to Make Memories
Further analysis showed that DNA fragments, along with other molecules resulting from the DNA damage, were released from the nucleus, after which the neurons’ TLR9 inflammatory pathway was activated; this pathway in turn stimulated DNA repair complexes to form at an unusual location: the centrosomes. These organelles are present in the cytoplasm of most animal cells and are essential for coordinating cell division. But in neurons — which don’t divide — the stimulated centrosomes participated in cycles of DNA repair that appeared to organize individual neurons into memory assemblies.
“Cell division and the immune response have been highly conserved in animal life over millions of years, enabling life to continue while providing protection from foreign pathogens,” Dr. Radulovic said. “It seems likely that over the course of evolution, hippocampal neurons have adopted this immune-based memory mechanism by combining the immune response’s DNA-sensing TLR9 pathway with a DNA repair centrosome function to form memories without progressing to cell division.”
Resisting Inputs of Extraneous Information
During the week required to complete the inflammatory process, the mouse memory-encoding neurons were found to have changed in various ways, including becoming more resistant to new or similar environmental stimuli. “This is noteworthy,” said Dr. Radulovic, “because we’re constantly flooded by information, and the neurons that encode memories need to preserve the information they’ve already acquired and not be ‘distracted’ by new inputs.”
Importantly, the researchers found that blocking the TLR9 inflammatory pathway in hippocampal neurons not only prevented mice from forming long-term memories but also caused profound genomic instability, i.e, a high frequency of DNA damage in these neurons.
“Genomic instability is considered a hallmark of accelerated aging as well as cancer and psychiatric and neurodegenerative disorders such as Alzheimer’s,” Dr. Radulovic said. “Drugs that inhibit the TLR9 pathway have been proposed for relieving the symptoms of long COVID. But caution needs to be shown because fully inhibiting the TLR9 pathway may pose significant health risks.”
The study is titled “Formation of memory assemblies through the DNA sensing TLR9 pathway.” Other Einstein authors are: Hui Zhang, Ph.D., Zorica Petrovic, B.A., Anna Carboncino, Ph.D., Kendra K. Parker, B.A., Thomas E. Bassett, Ph.D., Xusheng Zhang, M.S. The other contributors are: co-first author Vladimir Jovasevic, Ph.D., at Northwestern University, Chicago, IL; Maria Moltesen, Ph.D., Naoki Yamawaki, Ph.D., Hande Login, Ph.D., Joanna Kalucka, Ph.D., all at Aarhus University, Aarhus, Denmark; Farahnaz Sananbenesi, and Andre Fischer, Ph.D., at University Medical Center, Göttingen, Germany.

Young adults who were prescribed stimulant medications for attention-deficit/hyperactivity disorder (ADHD) were significantly more likely to develop cardiomyopathy (weakened heart muscle) compared with those who were not prescribed stimulants, in a study presented at the American College of Cardiology’s Annual Scientific Session.
The study found that people prescribed stimulants such as Adderall and Ritalin were 17% more likely to have cardiomyopathy at one year and 57% more likely to have cardiomyopathy at eight years compared with those who were not taking these medications. Cardiomyopathy involves structural changes in the heart muscle that weaken its pumping ability. It can cause a person to tire easily and limit their ability to perform daily tasks, and it often worsens over time.
However, researchers said that the overall risk of cardiomyopathy remained relatively low even when stimulants were used long-term. They said the findings do not necessarily point to a need for clinicians to change their approach to screening patients or prescribing stimulants.
“The longer you leave patients on these medications, the more likely they are to develop cardiomyopathy, but the risk of that is very low,” said Pauline Gerard, a second-year medical student at the University of Colorado School of Medicine in Aurora, Colorado, and the study’s lead author. “I don’t think this is a reason to stop prescribing these medications. There’s very little increased risk of these medications over the long term; it’s a real risk, but it’s small.”
ADHD is one of the most common neurodevelopmental disorders in children, affecting about 1 out of 10 American children aged 3 to 17, and can continue into adulthood. It is typically treated with behavioral therapy initially, which may be combined with stimulant or non-stimulant medications to help control behaviors that interfere with daily life and relationships. Stimulant medications can elevate blood pressure by causing the heart to beat faster and with greater force.
Most previous studies assessing the safety of stimulant medications have focused on the first year or two of use and found no evidence of harm to the heart. Since many patients are prescribed these medications in early childhood and continue taking them into adulthood, this new study was designed to assess their potential to cause harm over a longer period of time, Gerard said.
Using the TriNetX research database that includes information from about 80 hospitals across the U.S., researchers analyzed data from people diagnosed with ADHD between 20-40 years of age. Individuals with the presence or absence of a prescription for stimulant medications along with rates of cardiomyopathy that could potentially be linked to stimulant use were included. Those with heart damage caused by other known factors, such as cancer treatments, were excluded.

For the analysis, the researchers paired each person who had been prescribed stimulants with an individual who had not been prescribed stimulants but was as similar as possible in all other respects, such as age, sex and other health conditions. Overall, 12,759 pairs were created and were followed for at least 10 years. Of these pairs, people prescribed stimulants were found to be significantly more likely to develop cardiomyopathy throughout the 10-year follow-up period, with the gap growing larger each year except the last two, when it narrowed slightly.
Despite the significant gap, the overall prevalence of cardiomyopathy was still quite low in both groups. After being prescribed stimulants for 10 years, 0.72% (less than three-quarters of one percent) of patients developed cardiomyopathy, compared with 0.53% (a little over half of one percent) among those who were not prescribed stimulants.
To put the numbers into context, Gerard said, “You can have almost 2,000 patients on these medications for a year and you might only cause one of them to have a cardiomyopathy that they otherwise would not have had, but if you leave them on it for 10 years, 1 in 500 will have that happen.”
At these levels, researchers said the study does not suggest that aggressive testing for cardiovascular risk is warranted before prescribing stimulants, given that the potential benefits of testing must be balanced against the risks and costs. They suggest that further studies could help to identify subgroups of patients at greater risk who may benefit from future screening approaches.
Gerard said that it could also be helpful to study potential differences among different types of ADHD medications and different types of cardiomyopathies.

Sleeping fewer than seven hours is associated with a higher risk of developing high blood pressure over time, according to a study presented at the American College of Cardiology’s Annual Scientific Session.
While the association between sleep patterns and high blood pressure has been reported, evidence about the nature of this relationship has been inconsistent, according to researchers. The current analysis pools data from 16 studies conducted between January 2000 and May 2023, evaluating hypertension incidence in 1,044,035 people from six countries who did not have a prior history of high blood pressure over a median follow-up of five years (follow-up ranged from 2.4 to 18 years). Short sleep duration was significantly associated with a higher risk of developing hypertension after adjusting for demographic and cardiovascular risk factors, including age, sex, education, BMI, blood pressure, smoking status etc. Furthermore, the association was found to be even stronger for those getting less than five hours of sleep.
“Based on the most updated data, the less you sleep — that is less than seven hours a day — the more likely you will develop high blood pressure in the future,” said Kaveh Hosseini, MD, assistant professor of cardiology at the Tehran Heart Center in Iran and principal investigator of the study. “We saw a trend between longer sleep durations and a greater occurrence of high blood pressure, but it was not statistically significant. Getting seven to eight hours of sleep, as is recommended by sleep experts, may be the best for your heart too.”
The study found that sleeping less than seven hours was associated with a 7% increased risk of developing high blood pressure, which spiked to 11% when reported sleep duration was less than five hours. By comparison, diabetes and smoking are known to heighten one’s risk of hypertension by at least 20%, Hosseini said.
While the study did not look at why this might be the case, Hosseini said that disrupted sleep could be to blame. For example, he said lifestyle habits or comorbid conditions such as overeating, alcohol use, nightshift work, certain medication use, anxiety, depression, sleep apnea or other sleep disorders may be factors.
Researchers were surprised there were no age-based differences in the association between sleep duration and hypertension given that sleep patterns tend to shift with age. The age of the participants ranged from 35.4 years to 60.9 years and more than half (61%) were female. When compared with men, females who reported less than seven hours of sleep had a 7% greater risk of developing high blood pressure.
“Getting too little sleep appears to be riskier in females,” Hosseini said. “The difference is statistically significant, though we are not sure it’s clinically significant and should be further studied. What we do see is that lack of good sleep patterns may increase the risk of high blood pressure, which we know can set the stage for heart disease and stroke.”
It’s important for people to talk with their health care team about their sleep patterns, especially if they have disrupted sleep that might be due to obstructive sleep apnea. Sleep apnea has been tied to higher rates of high blood pressure, stroke and coronary artery disease.
This study has several limitations, including that sleep duration was based on self-reported questionnaires, so changes in sleep duration over the follow-up period were not assessed. Moreover, there were variations in how short sleep duration was defined between the studies (fewer than five or six hours).
“Further research is required to evaluate the association between sleep duration and high blood pressure using more accurate methods like polysomnography, a method for evaluating sleep quality more precisely,” Hosseini said. “Moreover, the variations in reference sleep duration underline the need for standardized definition in sleep research to enhance the comparability and generalizability of findings across diverse studies.”

Researchers at Trinity College Dublin have recovered remarkably preserved microbiomes from two teeth dating back 4,000 years, found in an Irish limestone cave. Genetic analyses of these microbiomes reveal major changes in the oral microenvironment from the Bronze Age to today. The teeth both belonged to the same male individual and also provided a snapshot of his oral health.
The study, carried out in collaboration with archaeologists from the Atlantic Technological University and University of Edinburgh, was published today in journal Molecular Biology and Evolution. The authors identified several bacteria linked to gum disease and provided the first high-quality ancient genome of Streptococcus mutans, the major culprit behind tooth decay.
While S. mutans is very common in modern mouths, it is exceptionally rare in the ancient genomic record. One reason for this may be the acid-producing nature of the species. This acid decays the tooth, but also destroys DNA and stops plaque from fossilising. While most ancient oral microbiomes are retrieved from fossilised plaque, this study targeted the tooth directly.
Another reason for the scarcity of S. mutans in ancient mouths may be the lack of favorable habitats for this sugar-loving species. An uptick of dental cavities is seen in the archaeological record after the adoption of cereal agriculture thousands of years ago, but a far more dramatic increase has occurred only in the past few hundred years when sugary foods were introduced to the masses.
The sampled teeth were part of a larger skeletal assemblage excavated from Killuragh Cave, County Limerick, by the late Peter Woodman of University College Cork. While other teeth in the cave showed advanced dental decay, no cavities were visible on the sampled teeth. However, one tooth produced an unprecedented amount of S. mutans DNA, a sign of an extreme imbalance in the oral microbial community.
“We were very surprised to see such a large abundance of S. mutans in this 4,000-year-old tooth,” said Dr Lara Cassidy, an assistant professor in Trinity’s School of Genetics and Microbiology, and senior author of the study. “It is a remarkably rare find and suggests this man was at a high risk of developing cavities right before his death.”
The researchers also found that other streptococcal species were virtually absent from the tooth. This indicates the natural balance of the oral biofilm had been upset — mutans had outcompeted the other streptococci leading to the pre-disease state.

The team also found evidence to support the “disappearing microbiome” hypothesis, which proposes modern microbiomes are less diverse than those of our ancestors. This is cause for concern, as biodiversity loss can impact human health. The two Bronze Age teeth produced highly divergent strains of Tannerella forsythia, a bacteria implicated in gum disease.
“These strains from a single ancient mouth were more genetically different from one another than any pair of modern strains in our dataset, despite the modern samples deriving from Europe, Japan and the USA,” explained Iseult Jackson, a PhD candidate at Trinity, and first author of the study. “This represents a major loss in diversity and one that we need to understand better.”
Very few full genomes from oral bacteria have been recovered prior to the Medieval era. By characterising prehistoric diversity, the authors were able to reveal dramatic changes in the oral microenvironment that have happened since.
Dr Cassidy added: “Over the last 750 years, a single lineage of T. forsythia has become dominant worldwide. This is the tell-tale sign of natural selection, where one strain rises rapidly in frequency due to some genetic advantage it holds over the others. T. forsythia strains from the industrial era onwards contain many new genes that help the bacteria colonise the mouth and cause disease.
“S. mutans has also undergone recent lineage expansions and changes in gene content related to pathogenicity. These coincide with humanity’s mass consumption of sugar, although we did find that modern S. mutans populations have remained more diverse, with deep splits in the S. mutans evolutionary tree pre-dating the Killuragh genome.”
The scientists believe this is driven by differences in the evolutionary mechanisms that shape genome diversity in these species.
“S. mutans is very adept at swapping genetic material between strains,” said Dr Cassidy. “This means an advantageous innovation can be spread across S. mutans lineages like a new piece of tech. This ability to easily share innovations may explain why this species retains many diverse lineages without one becoming dominant and replacing all the others.”
In effect, both these disease-causing bacteria have changed dramatically from the Bronze Age to today, but it appears that very recent cultural transitions in the industrial era have had an inordinate impact.