Publisher Health

Teens from larger families have poorer mental health than those with fewer siblings, according to a large analysis of children in the United States and China.
The details of the pattern vary depending on factors such as the spacing of sibling ages and the age of the siblings.
But the fact that the overall pattern was found in both countries is striking, said Doug Downey, lead author of the study and professor of sociology at The Ohio State University.
“Our results couldn’t have been easily predicted before we did the study,” Downey said.
“Other studies have shown that having more siblings is associated with some positive effects, so our results were not a given.”
Downey conducted the study with Rui Cao, a doctoral student in sociology at Ohio State. Their results were published recently in the Journal of Family Issues.
Their Chinese analysis draws on more than 9,400 eighth graders from the China Education Panel Study. In the United States, they analyzed over 9,100 American eighth graders from the Early Childhood Longitudinal Study — Kindergarten Cohort of 1988.

The average youth in China has nearly .7 fewer siblings than the average American youth (.89 compared to 1.6).
Consistent with what was expected because of China’s One Child Policy, about one-third of Chinese children are only children (34%), compared to just 12.6% of American children.
In both countries, researchers asked students (average age of 14) a variety of questions about their mental health, although the questions were different in China and the United States.
In China, teens with no siblings showed the best mental health, while in the United States, those with no or one sibling had similar mental health.
Some issues could only be analyzed using the U.S. data.
Results in the U.S. showed that half and full siblings are both linked to poorer mental health.

And having older siblings and siblings closely spaced in age tended to have the worst impacts on well-being, the U.S. data found. Siblings born within one year of each other had the strongest negative association with mental health.
Why are more siblings linked with poorer mental health?
Downey said the overall findings fits with the “resource dilution” explanation.
“If you think of parental resources like a pie, one child means that they get all the pie — all the attention and resources of the parents,” he said.
“But when you add more siblings, each child gets fewer resources and attention from the parents, and that may have an impact on their mental health.”
The fact that closely spaced siblings have the most negative impact bolsters that explanation. Children who are near the same age will be competing for the same types of parental resources, he said.
Another possibility, though, is that the families that have many versus few children are different in other ways that may reduce mental health for their kids — the so-called selectivity explanation.
The differences between China and the U.S. do provide some support for the selectivity explanation. In each country, children from families associated with the most socioeconomic advantage had the best mental health.
In China, that was children in one-child families, while in the U.S. it was children with zero or one sibling.
But the overall results still suggest that selectivity explanation falls short in accounting for what is happening.
“What we found is that when you add all the evidence up, the effect of siblings on mental health is more on the negative side than the positive side,” Downey said.
Downey noted that the data doesn’t get at the quality of sibling relationships. It is likely that higher-quality sibling relationships will be more beneficial to children and may have more positive effects on mental health.
While this study shows a negative impact of siblings, other research has shown that having more brothers and sisters is associated with better social skills among kindergarteners and a lower likelihood of divorce among adults.
“This combination of results is not easily explained. We still have more to learn about the impact of siblings,” Downey said.
“This is particularly important now as the U.S. and other countries have lower fertility rates. Understanding the consequences of growing up with fewer or no brothers and sisters is an increasingly important social issue.”

Outdoor humidity and temperature levels during pregnancy could affect the future blood pressure of the unborn child, according to new research by the University of Bristol, published in JACC: Advances.
The study, part of the LongITools project, has shown that exposure to relative humidity and temperature levels during pregnancy was related to blood pressure changes in the children. Higher relative humidity in pregnancy was associated with a steeper increase in blood pressure, and prenatal exposure to higher temperature with a slower increase in blood pressure, especially in childhood from age 3 to 10 years. Although an increase in blood pressure is normal during this age range, these weather-related factors were associated with a different rate of increase, especially in childhood.
Previous studies have mostly measured blood pressure at a single time point, predominantly focusing on single exposures, particularly air pollution. In this study, using repeated measures of blood pressure, researchers aimed to assess the association of a range of prenatal urban environmental exposures with changes in systolic and diastolic blood pressure from childhood to early adulthood.
The study analysed repeated blood pressure measurements in over 7,000 participants aged between 3 and 24 years from Bristol’s Children of the 90s study, a world-leading longitudinal study, to assess the relationship of various characteristics of the urban environment in pregnancy with blood pressure from childhood to early adulthood. Analyses were repeated in four independent European cohorts in over 9,000 individuals in Finland, France and the Netherlands.
The research team explored 43 different measures of noise, air pollution, built environment, natural spaces, traffic, meteorology, and unhealthy food environment, and found that prenatal outdoor temperature and humidity could influence changes in blood pressure, especially in childhood.
Overall, the study showed: Higher humidity was associated with a faster increase and higher temperature with a slower increase in systolic blood pressure in childhood. Higher humidity was associated with a faster increase in diastolic blood pressure in childhood.In the UK cohort, higher levels of air pollution were associated with a faster increase in diastolic blood pressure in childhood and a slower increase in adolescence, but this association was not replicated in other cohorts.

There was little evidence of an association of other urban environmental exposures with changes in systolic or diastolic blood pressure.
Dr Ana Gonçalves Soares, Research Fellow in Epidemiology in the Bristol Medical School: Population Health Studies and MRC IEU and lead researcher, said: “Children with higher blood pressure are more likely to have higher blood pressure as adults, which can increase the risk of heart disease and stroke as well as kidney disease and vascular dementia.
“Previous studies have already shown that some urban environmental exposures during pregnancy are associated with blood pressure in childhood. We were able to expand that further and explore whether these environmental exposures are also associated with trajectories (changes) of blood pressure from childhood to early adulthood.
“The findings suggest that humidity and temperature during pregnancy could change the child’s blood pressure. Further work is needed to be carried out to understand how weather-related conditions during pregnancy can affect the child’s blood pressure to inform strategies to prevent cardiovascular disease in later adulthood related to prenatal environmental exposures.”

Tianeptine, found at convenience stores, at smoke shops and online, can mimic an opioid. It is among a growing class of substances that are difficult to control.The young father headed across the parking lot to join the other parents meeting their children’s new preschool teachers. After a few steps, he began sweating and twitching. As the sky reeled, he staggered back to the car, desperate to lie down in the back seat and breathe, hidden by tinted windows.“Did you take something?” his wife, Anne, shouted at him while dialing 911. Eric, 26, had completed rehab earlier in the summer.“The shot! The shot!” he groaned, just before he hit the ground and blacked out.In the emergency room of a nearby hospital in southern New Jersey, doctors tried to revive him with a defibrillator.“What’s he on?” they yelled at Anne.She showed them a shot-size bottle of the cherry-flavored elixir she had fished out of the car. It was labeled Neptune’s Fix, which Eric had bought at a local convenience store.“What the hell is that?” a doctor asked.Neptune’s Fix features an ingredient called tianeptine — popularly known as gas-station heroin.Often sold as a dietary supplement and promoted by retailers as a mood booster and focus aid, tianeptine is among a growing, unregulated class of potentially addictive products available in gas stations, convenience stores and smoke shops and across the internet. They typically include synthetic pharmaceuticals and plant-derived substances.Some, like kratom and phenibut, can be addictive and, in rare cases, fatal. They often originate in other countries, including Indonesia and Russia, where they are commonly used, even prescribed, for mood management. But the Food and Drug Administration has not approved them as medicines in the United States.“Tianeptine is an emerging threat,” said Kaitlyn Brown, clinical managing director of America’s Poison Centers, which represents and collects data from 55 centers nationwide. “We have people who are able to get a substance that’s not well regulated, that has abuse potential and that, in high doses, can cause similar effects to opioids, leading to really harmful outcomes.”At least nine states have banned or severely restricted tianeptine, including Florida, Michigan and Ohio. In late November, the F.D.A. issued a nationwide alert about Neptune’s Fix specifically and tianeptine in general, telling people not to take it and warning that it had been associated with overdoses and deaths.Tianeptine, which also appears as a concentrated powder or an ingredient in products such as Tianaa, Zaza and Pegasus, “is illegally sold with claims to improve brain function and treat anxiety, depression, pain, opioid use disorder and other conditions,” the agency’s warning said.The F.D.A. loosely oversees dietary supplements, an expanding universe of some 50,000 products that includes minerals, vitamins and compounds like melatonin. But the agency does not evaluate supplements for safety or effectiveness; it can only forbid manufacturers to market them as medical treatments. It requires product labels making health claims to list ingredients and include boilerplate disclaimers, such as noting that the product has not been reviewed by the F.D.A. The agency does not review those labels before a product is released.Because the F.D.A.’s enforcement powers are limited by law, many products with tianeptine have long skirted labeling requirements. Although the F.D.A. has explicitly said, for example, that tianeptine does not qualify as a dietary supplement, the labels of some brands, like Tianaa, still make that claim.“There are now at least a dozen different products that are foreign drugs being openly marketed as dietary supplements right under the F.D.A.’s eyes, without them being able to stop the sales,” said Dr. Pieter Cohen, an associate professor at Harvard Medical School who studies the regulation of supplements.Tianeptine is a drug developed by French researchers in the 1960s as an antidepressant. It is approved in low doses for that use in many European, Asian and Latin American countries.But at higher doses, it also works much as an opioid does, delivering short-lived euphoria. In the United States, many people take tianeptine under the widespread, mistaken belief that it is a safe alternative to street opioids like fentanyl or heroin, or even a way to taper off using them. On social media sites like Reddit, its merits are hotly debated, with more than 5,000 people subscribing to a “Quitting Tianeptine” forum.“People develop a tolerance very quickly, and so they rapidly start advancing the dosing,” said Dawn Sollee, a clinical toxicologist and director of the Poison Control Center in Jacksonville, Fla. “They will set alarms to wake themselves every two hours to take tianeptine pills so they do not go into withdrawal. And then they have to keep taking more and more just to stay functional.”Kratom leaves for sale in a market in Bangkok in 2021.Narong Sangnak/EPA, via ShutterstockExpenses can mount swiftly, along with dangers. At a convenience store in Montclair, N.J., recently, 15 capsules of Tianaa Red cost $34. A bottle of Neptune’s Fix, which comes in lemon, tropical, cherry or chocolate-vanilla flavor, runs about $16. A salesman at a roadside smoke shop farther west said customers typically purchased 12-bottle boxes. A salesman at another roadside shop said that one customer bought 10 boxes each week — whether for resale or personal use, he did not know.Determining the number of cases of tianeptine abuse is challenging, because hospitals do not test for it. Reports to poison-control centers are voluntary, typically made by a worried relative, so officials say the numbers represent a drastic undercount.But case reports are increasing. In 2013, only four cases of tianeptine exposure were reported nationwide. In 2023, 391 cases were reported, according to America’s Poison Centers. New Jersey, which typically has one report a year, received 27 in 2023, with patients ranging in age from 20 to 69.“Some people apparently think it can help with chronic pain instead of having to use an opioid, which might explain the older demographic,” said Dr. Diane Calello, medical director of the New Jersey Poison Control Center.Similarly to many illicit drugs, tianeptine is often sloppily mixed with unlabeled ingredients, such as potent synthetic cannabinoids. That is one reason overdose symptoms appear to range widely, poison-control medical directors said, including clamminess, nausea, low blood pressure and unconsciousness as well as seizures and severe stomach cramps.Sometimes naloxone, a drug that reverses opioid overdoses, can be effective in reviving patients, they said — and sometimes not. At least four deaths have been associated with tianeptine.About a year ago, Dr. Raymond Pomm, an addiction psychiatrist at Gateway Community Services in Jacksonville, saw his first tianeptine patient. To treat the patient’s withdrawal symptoms, he tried buprenorphine, a medication that dulls opioid cravings. He said he found that it helped patients to manage withdrawal from tianeptine and to maintain abstinence. “Since it was being sold in stores, I thought, It can’t be that bad,” said Eric, a man who suffered severe tianeptine symptoms, about Neptune’s Fix.Hannah Beier for The New York TimesLast summer, after Eric completed rehab for kratom, a potentially addictive herb from Southeast Asia that is readily available in convenience stores and smoke shops, doctors recommended medication for anxiety and depression. But Eric, a corporate salesman from a suburb in South Jersey, was determined to stay away from mood-altering prescriptions, to which he had been addicted in the past.At a tobacco shop, he spotted Neptune’s Fix. A salesman said it could help with his mood and would not hook him.“Since it was being sold in stores, I thought it can’t be that bad,” said Eric, who, like Anne, asked to be identified by his middle name to protect his family’s privacy. “You know, an energy drink type of thing.”After tossing back a shot, he felt better almost immediately: more talkative, happy, confident.But soon, Eric said, “I couldn’t stop taking it.”Within a few weeks, he was up to five bottles a day, spending over $400 a week. His energy was flagging. Though he was a former college athlete still accustomed to working out daily, he now could not even get himself to the gym.When he tried quitting cold turkey, withdrawal hit him with cold sweats, muscle aches, restlessness and irritability.Weeks after he collapsed in the preschool parking lot, doctors from the New Jersey Poison Control Center tested the contents of his Neptune’s Fix bottles. Results included synthetic cannabinoids and other unlisted ingredients as well as tianeptine.The F.D.A. sent warnings in 2021 and 2022 to two companies that it said were “illegally marketing tianeptine products as dietary supplements and unapproved drugs.”But enforcement requires huge resources, in part because manufacturers and purveyors can be difficult to track down. An inquiry from The New York Times to the makers of Neptune’s Fix submitted through its website received no response. The Sheridan, Wyo., location listed on the company’s bottles is an address for a registration agent for numerous companies.Regulatory experts disagree about how the F.D.A. should grapple effectively with tianeptine and other supplements. Some say the agency should establish a strict registry of approved supplements.In interviews, some poison-center directors did not endorse a full ban of tianeptine, saying that could lead to dangerous underground trafficking. Educating emergency responders and consumers about inherent risks in such products would be a more effective course, they said.Getting tianeptine off store shelves, they added, would be not only a staggering task but also of limited utility because customers could simply buy it from the most convenient store of all — the internet.While Eric was recovering from tianeptine poisoning, Anne stormed over to the local smoke shop where he had bought it.“My husband’s in the hospital because of this product and you’re still going to keep it on the shelves?” she yelled.“Yes,” she said the owner replied, “because people want it and we need to make money.”

Researchers at Karolinska Institutet in Sweden have shown that nasal drops with IgA antibodies can protect mice from SARS-CoV-2 infection. The results imply a new way to protect individuals at high risk from different variants of the SARS-CoV-2 virus and possibly other infections. The study is published in the Proceedings of the National Academy of Sciences.
Different types of antibodies have different functions in the body. IgA antibodies are part of the so-called adaptive immune system and reside naturally in the mucosal membranes of the airways. Absence or low levels of mucosal IgA is known to be associated with an increased risk of SARS-CoV-2 breakthrough infections.
The current COVID-19 vaccines mainly stimulate an IgG antibody response in the body, and earlier studies have shown that their ability to protect against infection with the new Omicron variants of the virus is limited.
To overcome this, the group led by professor Qiang Pan-Hammarström at Karolinska Institutet used genetic engineering to create IgA antibodies that bind to the SARS-CoV-2 spike protein in a similar way to the IgG antibodies.
Neutralized the virus effectively
Mice infected with the Omicron variant received the IgA antibody treatment through nasal administration. The nasal drops significantly diminished the virus load in the trachea and lungs of the infected mice. The IgA antibodies were shown to bind stronger to the spike protein of SARS-CoV-2 and were more effective in neutralizing the virus compared to the original IgG antibodies.
“The results show that these genetically engineered antibodies can strengthen the protection against new virus variants, but they are not intended to replace current vaccines,” says Harold Marcotte, associate professor at the Department of Medical Biochemistry and Biophysics, Karolinska Institutet, and the first author of the paper.

“Traditional vaccines elicit an active immune response from the body, whereas this is a passive immunization strategy,” he continues. “An active immunization approach that induces a mucosal immune response would be ideal, but hopefully our approach is suitable for protecting the most vulnerable individuals, like the elderly or immunocompromised persons.”
Promising strategy for other infections
There are also hopes that the method can be used to neutralize other current and emerging variants of the virus.
“We believe that this will be a very promising strategy, not only for COVID-19 and the new variants, but also for other infectious diseases, including influenza and other respiratory infections and gastric mucosal infections such as Helicobacter pylori, where there is no vaccine available at the moment,” says Qiang Pan-Hammarström, professor at the same department and last author of the paper.
The study was conducted within the European research consortium ATAC and through a collaborative effort between Sweden and China including Linköping University, Peking University, Guangzhou Institutes of Biomedicine and Health, Fudan University, Peking Union Medical College, Wuhan Institute of Virology, and Kunming Institute of Zoology.
It was funded by EU’s Horizon 2020 research and innovation program, a joint VR-NCSF funding, the Knut and Alice Wallenberg Foundation and the Swiss National Science Foundation grant BRIDGE. Some of the authors are listed as inventors of patents regarding antibody treatment.

Starting a new year, many people pledge to enact self-care routines that improve their appearance. And facial sheet masks soaked in skin care ingredients provide an easy way to do this. However, these wet masks and their waterproof packaging often contain plastics and preservatives. Now, a study in ACS Applied Materials & Interfaces reports a dry-packaged hydrating facial mask that is made of biobased and sustainable materials.
Consumers in the beauty industry are increasingly concerned about the sustainability and sourcing of personal care items, in terms of both products’ ingredients and packaging. Facial sheet masks are popular cosmetic products advertised to benefit and enhance the skin. But they are typically made with plastic backing fabrics and are packaged with wet ingredients, requiring preservatives and disposable water-tight pouches. A more environmentally friendly option would be to package the facial masks dry. So, Jinlain Hu and coworkers aimed to design a facial sheet mask with biobased materials that could be enveloped in paper and later activated to deliver moisture and nutrients.
The researchers developed a facial mask with a sheet of plant-based polylactic acid (PLA), which could repel water, and they coated it in a layer of gelatin mixed with hyaluronic acid and green tea extract. They deposited the top layer as either tiny fibers or microspheres, using electrospinning or electrospray, respectively, and tested how well the masks could transfer moisture. They found: Water droplets did not pass through the masks without skin contact, regardless of which side a water droplet was placed on. Contact with skin initiated one-way water transport from PLA to gelatin to skin, but only for masks coated with gelatin-based microspheres. Placing the mask on moistened, rather than dry, skin improved water delivery through the mask.Finally, the team investigated how its mask’s ingredients impacted mouse cells as a proxy for reactions on skin. Fewer cells showed signals of aging when grown on the mask compared with cells grown in control conditions; the researchers attribute this to the antioxidant properties of the green tea extracts. The team says the beneficial properties of the natural ingredients and the one-way moisture-delivery design make this mask a promising alternative with a lesser environmental impact compared to traditional, wet-packed products.
The authors acknowledge funding from the City University of Hong Kong, the National Natural Science Foundation of China, and Shenzhen-Hong Kong-Macau Science & Technology Fund.

Reducing stimulant use was associated with significant improvement in measures of health and recovery among people with stimulant use disorder, even if they did not achieve total abstinence. This finding is according to an analysis of data from 13 randomized clinical trials of treatments for stimulant use disorders involving methamphetamine and cocaine. Historically, total abstinence has been the standard goal of treatment for substance use disorders, however, these findings support the growing recognition that a more nuanced perspective on measuring treatment success may be beneficial.
The study, published in Addiction, was led by scientists at the Johns Hopkins Bloomberg School of Public Health, Baltimore, in collaboration with researchers at the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.
Researchers found that transitioning from high use (five or more days a month) to lower use (one to four days a month) was associated with lower levels of drug craving, depression, and other drug-related challenges compared to no change in use. These results suggest that reduction in use of methamphetamine or cocaine, in addition to abstinence, is a meaningful surrogate or intermediate clinical outcome in medication development for stimulant addiction. Unlike other substance use disorders, such as opioid use disorder or alcohol use disorder, there are currently no U.S. Food and Drug Administration-approved pharmacological treatments for stimulant use disorders.
“These findings align with an evolving understanding in the field of addiction, affirming that abstinence should be neither the sole aim nor only valid outcome of treatment,” said NIDA Director Nora Volkow, M.D. “Embracing measures of success in addiction treatment beyond abstinence supports more individualized approaches to recovery, and may lead to the approval of a wider range of medications that can improve the lives of people with substance use disorders.”
Temporary returns to use after periods of abstinence are part of many recovery journeys, and relying exclusively on abstinence as an outcome in previous clinical trials may have masked beneficial effects of treatment. To help address this research gap, investigators analyzed data from previous clinical trials to study the effects of transitioning to reduced drug use or abstinence on a broad range of health measures. Researchers analyzed data from 13 randomized clinical trials evaluating the impact of potential pharmacological medications for stimulant use disorders, which included more than 2,000 individuals seeking treatment for cocaine or methamphetamine use disorders at facilities across the United States. The trials were of varying duration and were undertaken from 2001 to 2017.
Researchers compared “no reduced use,” “reduced use,” and “abstinence” in association with multiple health outcomes, such as severity of drug-related symptoms, craving, and depression. The study found that more participants reduced the frequency of primary drug use (18%) than achieved abstinence (14%). While abstinence was associated with the greatest clinical improvement, reduced use was significantly associated with multiple measures of improvements in psychosocial functioning at the end of the trials, such as a 60% decrease in craving for the primary drug, 41% decrease in drug-seeking behaviors, and a 40% decrease in depression severity, compared to the beginning of the trial.
These findings suggest that improvements in health and functioning can occur with reduced use and should be considered in the development and approval of treatments for substance use disorders. Research on alcohol use disorder has shown similar results, with studies finding that transitioning from high-risk to low-risk drinking is associated with functional improvement and fewer mental and general health consequences caused by alcohol. As a result, a reduced number of heavy drinking days is already recognized as a meaningful clinical outcome in medication development for alcohol use disorder.

“With addiction, the field has historically acknowledged only the benefits of abstinence, missing opportunities to celebrate and measure the positive impacts of reduced substance use,” said Mehdi Farokhina, M.D., M.P.H., a staff scientist in the NIDA Intramural Research Program, and author on the paper. “This study provides evidence that reducing the overall use of drugs is important and clinically meaningful. This shift may open opportunities for medication development that can help individuals achieve these improved outcomes, even if complete abstinence is not immediately achievable or wanted.”
The authors note that the study did not include behavioral treatment trials, which were too varied to harmonize their data. In addition, the study featured only people who enrolled in clinical trials, which could limit generalizability. Additional research is needed to understand the potential clinical benefits of reduced drug use, along with other harm reduction-based indicators of clinical improvement in real-world populations. The authors highlight that the findings of this study should encourage researchers to re-evaluate treatment outcome measures in their studies and consider non-abstinence treatment outcomes in the development of new medications for the treatment of stimulant use disorders. The authors also write that these new findings need to be replicated in other contexts with additional substance use disorders such as opioid use disorder.
“By promoting an understanding of addiction as a treatable disorder with multifaceted causes, society can work towards providing better support, resources, and care for individuals on their way to recovery,” said Masoumeh Aminesmaeili, M.D., lead author of the paper. “This approach is not only compassionate, but also clinically valid in addressing the complex nature of addiction.”
For more information on substance and mental health treatment programs in your area, call the free and confidential National Helpline 1-800-662-HELP (4357) or visit: https://www.findtreatment.gov

Like a criminal entering a witness protection program, cancer cells can shed their past and take on a new identity. Detecting such an identity-switch is particularly challenging when metastatic castration-resistant prostate cancer (CRPC) advances from adenocarcinoma to neuroendocrine prostate cancer (NEPC), a very difficult cancer to treat.
Now, however, researchers at Dana-Farber Cancer Institute and the University of Trento, Italy, have developed a blood test, described in Cancer Discovery, that can reliably detect NEPC and differentiate it from CRPC-adenocarcinoma (CRPC-adeno).
NEPC is currently diagnosed using a biopsy of tumor tissue from a metastatic tumor site. Yet, it isn’t always clear to clinicians when to do a biopsy. Further, biopsies may be unreliable since metastatic tumors are often heterogeneous.
“As prostate cancer treatments get more effective, we expect the emergence of different types of treatment resistance like neuroendocrine prostate cancer that help them evade treatment,” says co-lead author Himisha Beltran, MD, associate professor of medicine, Lank Center for Genitourinary Oncology and the Division of Molecular and Cellular Oncology, Dana-Farber Cancer Institute. “We hope this blood test can be used by clinicians to determine if a patient is developing neuroendocrine prostate cancer.”
Approximately 10-15% of patients with metastatic prostate cancer develop NEPC. The transition involves a shift from cancer cells that are dependent on hormones called androgens to cancer cells that no longer even recognize androgens.
“They can stop expressing the androgen receptor,” says Beltran. “They shut down their hormone-driven identity and they turn on a new identity as a way to develop resistance to treatment.”
In previous research, the international team studied tissue samples from biopsies to identify the genetic and epigenetic changes related to this transition. They found that, across the whole genome, specific epigenetic changes, in the form of DNA methylation changes that switch genes on or off, distinguish CRPC-adeno from NEPC.

These epigenetic changes can be detected in blood because the body is constantly shedding fragments of dead cells into the bloodstream. Those cells come from all over the body, including from tumors. The fragments include bits of DNA, called cell free DNA (cfDNA), along with whatever epigenetic tags and structures were attached to them when the cell died.
Beltran collaborated with a computational team at the University of Trento, led by Francesca Demichelis, PhD, co-lead author on the study, to create a blood panel test, called NEMO (NEuroendocrine MOnitoring panel). “The test selectively probes cfDNA in blood plasma for relevant DNA fragments and measures their methylation,” says Demichelis. “Because the number of methylated regions needed to distinguish between normal, CRPC-adeno, and NEPC cells is small, the panel of genes sequenced by the test is minimal and efficient.”
NEMO reports two measures: the tumor fraction, a measure of disease burden based on the ratio of tumor DNA to normal DNA in the blood; and the tumor type, either CRPC-adeno or NEPC. The tumor type is reported as a score on a continuum because a patient’s cancer might be a mix of the two.
“It not only picks up the neuroendocrine phenotype but also can pick up subtypes in the middle, as tumors transition from one subtype to the other,” says Beltran.
Beltran’s team tested NEMO in several preclinical models of prostate cancer and in blood samples from multiple patient cohorts with known prostate cancer subtypes. The NEMO tumor type score identified subtypes with a high level of accuracy.
The team also evaluated NEMO in two clinical trials of patients with aggressive CRPC. The panel’s estimation of tumor fraction was consistent with other accepted measures of disease burden, suggesting that the test could be used to monitor response to treatment by revealing if a tumor is shrinking or not. This is especially valuable because, measures of disease burden, such as prostate-specific antigen levels, become unreliable when a tumor switches its identity to NEPC.

NEMO successfully identified patients with NEPC in the two clinical trials based on pathology reports. It also identified patients who had not been diagnosed with NEPC yet had signs of a transition to NEPC in their pathology reports.
“Now that we have robustly shown the accuracy of this panel test, we’re excited to apply it to clinical questions,” says Beltran. “We’d like to determine if this test can help us predict which patients respond to certain prostate cancer treatments, including precise treatments that target neuroendocrine prostate cancer.”
The information in a NEMO panel may also help clinicians select targeted treatments for patients or help investigators learn more about the disease. Further, adds Beltran, the test’s approach could potentially be applied to other forms of cancer to distinguish subtypes.
Longer term, Beltran and colleagues will take steps toward transitioning NEMO into a clinical test that physicians can order and use in practice.
Funding: The Prostate Cancer Foundation, National Cancer Institute, Fondazione AIRC per la Ricerca sul Cancro ETS, Cancer Research UK, United States Department of Defense, the Doris Duke Foundation, the Safeway Foundation, the V Foundation, and the Institute for Prostate Cancer Research.

Combining a biological heart and a silicone robotic pump, researchers created a biorobotic heart that beats like a real one, with a focus on a valve on the left side of the heart. The heart valve simulator, presented on January 10 in the journal Device, can mimic the structure, function, and motion of a healthy or diseased heart, allowing surgeons and researchers to demonstrate various interventions while collecting real-time data.
“The simulator has a huge benefit as a research tool for those who study different heart valve conditions and interventions,” says senior author and biomedical engineer Ellen Roche of the Massachusetts Institute of Technology. “It can serve as a surgical training platform for clinicians, medical students, and trainees, allow device engineers to study their new designs, and even help patients better understand their own disease and potential treatments.”
Before new interventions reach humans, they undergo rigorous testing in heart simulators and animal subjects. However, current heart simulators don’t completely capture the complexity of a heart and have a short shelf-life of two to four hours. Animal studies are expensive and time consuming, and the findings may not always translate to humans. The biorobotic heart can bridge these gaps as a less expensive method with a shelf life of months.
The researchers focused on mitral regurgitation, a disorder in which the valve between the left heart chambers doesn’t close properly — resulting in a leaky heart valve where blood can flow backwards. This condition, affecting about 24.2 million people worldwide, can cause shortness of breath, swelling in the limbs, and heart failure. Given the intricacy of the valve’s structure, surgeries to correct the disorder are highly complex, highlighting a need for effective technology and precise surgical techniques.
To better understand the mitral valve in healthy and diseased states, the team built a biorobotic heart based on a pig heart. The researchers replaced the heart muscle in the left chamber with a silicone-made soft robotic pump system actuated by air. When inflated, the system twists and squeezes the heart like real heart muscle, pumping artificial blood through a mock circulation system and simulating the beat of a biological heart.
When the team damaged the mitral valve in the biorobotic heart, it showed characteristics of a leaky heart valve. The team then had cardiac surgeons correct the damage with three different techniques: anchoring the flailing valve leaflet tissue with artificial chords, replacing the valve with a prosthetic valve, and implanting a device to help valve leaflet closing.
All three procedures were successful, bringing the pressure, flow, and heart function to normal. The system also enabled the research team to collect real-time data during surgery and is compatible with current imaging technologies used in the clinics. Because the artificial blood used in the system is clear, it also allows direct visualization of the procedure. The findings demonstrated the device as a new heart model.
“It was really interesting for the surgeons to see every step,” says Roche. “When you’re working with patients, you can’t visualize the process because there’s blood in the heart.” She foresees their heart model as a realistic environment for cardiac surgery training and practice.
Next, the team aims to optimize the current biorobotic heart system by shortening the production time and lengthening the shelf life even more. Instead of using a pig heart, they’re also exploring 3D printing technology to recreate a synthetic human heart for the system.
“Our biorobotic heart may help improve the device design cycle, allow rapid iterations, get things approved by regulatory bodies, and launch them into the market quickly,” says Roche. “Expediting and improving these processes will ultimately benefit patients.”

Researchers have created the world’s largest ancient human gene bank by analysing the bones and teeth of almost 5,000 humans who lived across western Europe and Asia up to 34,000 years ago.
By sequencing ancient human DNA and comparing it to modern-day samples, the international team of experts mapped the historical spread of genes — and diseases — over time as populations migrated.
The ‘astounding’ results have been revealed in four trailblazing research papers published today (10 January 2024) in the same issue of Nature and provide new biological understanding of debilitating disorders.
The extraordinary study involved a large international team led by Professor Eske Willerslev at the Universities of Cambridge and Copenhagen, Professor Thomas Werge at the University of Copenhagen, and Professor Rasmus Nielsen at University of California, Berkeley and involved contributions from 175 researchers from around the globe.
The scientists found: The startling origins of neurodegenerative diseases including multiple sclerosis Why northern Europeans today are taller than people from southern Europe How major migration around 5,000 years ago introduced risk genes into the population in north-western Europe — leaving a legacy of higher rates of MS today Carrying the MS gene was an advantage at the time as it protected ancient farmers from catching infectious diseases from their sheep and cattle Genes known to increase the risk of diseases such as Alzheimer’s and type 2 diabetes were traced back to hunter gatherers Future analysis is hoped to reveal more about the genetic markers of autism, ADHD, schizophrenia, bipolar disorder, and depressionNorthern Europe has the highest prevalence of multiple sclerosis in the world. A new study has found the genes that significantly increase a person’s risk of developing multiple sclerosis (MS) were introduced into north-western Europe around 5,000 years ago by sheep and cattle herders migrating from the east.
By analysing the DNA of ancient human bones and teeth, found at documented locations across Eurasia, researchers traced the geographical spread of MS from its origins on the Pontic Steppe (a region spanning parts of what are now Ukraine, South-West Russia and the West Kazakhstan Region).

They found that the genetic variants associated with a risk of developing MS ‘travelled’ with the Yamnaya people — livestock herders who migrated over the Pontic Steppe into North-Western Europe.
These genetic variants provided a survival advantage to the Yamnaya people, most likely by protecting them from catching infections from their sheep and cattle. But they also increased the risk of developing MS.
“It must have been a distinct advantage for the Yamnaya people to carry the MS risk genes, even after arriving in Europe, despite the fact that these genes undeniably increased their risk of developing MS,” said Professor Eske Willerslev, jointly at the Universities of Cambridge and Copenhagen and a Fellow of St John’s College, an expert in analysis of ancient DNA and Director of the project.
He added: “These results change our view of the causes of multiple sclerosis and have implications for the way it is treated.”
The age of specimens ranges from the Mesolithic and Neolithic through the Bronze Age, Iron Age and Viking period into the Middle Ages. The oldest genome in the data set is from an individual who lived approximately 34,000 years ago.
The findings provide an explanation for the ‘North-South Gradient’, in which there are around twice as many modern-day cases of MS in northern Europe than southern Europe, which has long been a mystery to researchers.

From a genetic perspective, the Yamnaya people are thought to be the ancestors of the present-day inhabitants of much of North-Western Europe. Their genetic influence on today’s population of southern Europe is much weaker.
Previous studies have identified 233 genetic variants that increase the risk of developing MS. These variants, also affected by environmental and lifestyle factors, increase disease risk by around 30 percent. The new research found that this modern-day genetic risk profile for MS is also present in bones and teeth that are thousands of years old.
“These results astounded us all. They provide a huge leap forward in our understanding of the evolution of MS and other autoimmune diseases. Showing how the lifestyles of our ancestors impacted modern disease risk just highlights how much we are the recipients of ancient immune systems in a modern world,” said Dr William Barrie, a postdoc in the University of Cambridge’s Department of Zoology and co-author of the paper.
Multiple sclerosis is a neurodegenerative disease in which the body’s immune system mistakenly attacks the ‘insulation’ surrounding the nerve fibres of the brain and spinal cord. This causes symptom flares known as relapses as well as longer-term degeneration, known as progression.
Professor Lars Fugger, a co-author of the MS study professor and consultant physician at John Radcliffe Hospital, University of Oxford, said: “This means we can now understand and seek to treat MS for what it actually is: the result of a genetic adaptation to certain environmental conditions that occurred back in our prehistory.”
Professor Astrid Iversen, another co-author based at the University of Oxford, said: “We now lead very different lives to those of our ancestors in terms of hygiene, diet, and medical treatment options and this combined with our evolutionary history means we may be more susceptible to certain diseases than our ancestors were, including autoimmune diseases such as MS.”
The Lundbeck Foundation GeoGenetics Centre — the resource underpinning the discoveries
The new findings were made possible by the analysis of data held in a unique gene bank of ancient DNA, created by the researchers over the past five years with funding from the Lundbeck Foundation.
This is the first gene bank of its kind in the world and already it has enabled fascinating new insights in areas from ancient human migrations, to genetically-determined risk profiles for the development of brain disorders.
By analysing the bones and teeth of almost 5,000 ancient humans, held in museum collections across Europe and Western Asia, the researchers generated DNA profiles ranging across the Mesolithic and Neolithic through the Bronze Age, Iron Age and Viking period into the Middle Ages. They compared the ancient DNA data to modern DNA from 400,000 people living in Britain, held in the UK Biobank.
“Creating a gene bank of ancient DNA from Eurasia’s past human inhabitants was a colossal project, involving collaboration with museums across the region,” said Willerslev.
He added: “We’ve demonstrated that our gene bank works as a precision tool that can give us new insights into human diseases, when combined with analyses of present-day human DNA data and inputs from several other research fields. That in itself is amazing, and there’s no doubt it has many applications beyond MS research.”
The team now plans to investigate other neurological conditions including Parkinson’s and Alzheimer’s diseases, and psychiatric disorders including ADHD and schizophrenia.
They have received requests from disease researchers across the world for access to the ancient DNA profiles, and eventually aim to make the gene bank open access.
The research was funded by a €8M grant from the Lundbeck Foundation, and conducted at the Lundbeck Foundation Geogenetics Centre at the University of Copenhagen.
Jan Egebjerg, Director of Research at the Lundbeck Foundation, said: “The rationale for awarding such a large research grant to this project, as the Lundbeck Foundation did back in 2018, was that if it all worked out, it would represent a trail-blazing means of gaining a deeper understanding of how the genetic architecture underlying brain disorders evolved over time. And brain disorders are our specific focus area.”

Published11 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, SayoStudioBy Philippa RoxbyHealth reporterWhy are diseases more common in some parts of Europe than others, and why are northern Europeans taller than their southern counterparts?An international team of scientists say they have unearthed the answer in the DNA of ancient teeth and bones.The genes which protected our ancestors from animal diseases now raise the risk of multiple sclerosis (MS). The researchers call their discovery “a quantum leap” in understanding the evolution of the disease.And they say it could change opinions on what causes MS, and have an impact on the way it is treated. Why look at MS?There are about twice as many cases of multiple sclerosis per 100,000 people in north-western Europe, including the UK and Scandinavia, compared with southern Europe.Researchers from the universities of Cambridge, Copenhagen and Oxford spent more than 10 years delving into archaeology to investigate why.MS is a disease where the body’s own immune cells attack the brain and spinal cord, leading to symptoms like muscle stiffness and problems walking and talking.They discovered that genes which increase the risk of MS entered into north-western Europe about 5,000 years ago via a massive migration of cattle herders called Yamnaya.Image source, Getty ImagesThe Yamnaya came from western Russia, Ukraine and Kazhakstan, and moved west into Europe, says one of four Nature journal papers published on the topic.The findings “astounded us all”, said Dr William Barrie, paper author and expert in computational analysis of ancient DNA at University of Cambridge.At the time, the gene variants carried by the herding people were an advantage, helping to protect them against diseases from their sheep and cattle.Nowadays, however, with changing lifestyles and diets, these gene variants have taken on a different role.In the present day, they mean a higher risk of developing certain diseases, such as MS.The research project was a huge undertaking – genetic information was extracted from ancient human remains found in Europe and Western Asia, and compared with the genes of hundreds of thousands of people living in the UK today. In the process, a bank of DNA from 5,000 ancient humans, kept in museum collections across many countries, has now been set up to help future research. ‘Find sweet spot’Prof Lars Fugger, paper author and MS doctor at the John Radcliffe Hospital in Oxford, says the discovery helps “demystify” the disease.”MS is not caused by mutations – it’s driven by normal genes to protect us against pathogens,” he explains.Vaccinations, antibiotics and higher standards of hygiene have changed the disease landscape completely – many diseases have disappeared and people are living decades longer.The researchers say modern immune systems may now be more susceptible to autoimmune diseases, like MS, which are on the rise.Drugs currently used to treat MS target the body’s immune system, but the downside is the risk of suppressing it so much that patients struggle to fight off infections.When treating it, we are up against evolutionary forces, Prof Fugger says.”We need to find the sweet spot where there is a balance with the immune system, rather than wiping it out.”Image source, Nature / University of CopenhagenThe team now plans to look for other diseases in ancient DNA and follow them back in time.Their research could reveal more about the origins of autism, ADHD, bipolar disorder and depression.Another Nature paper uncovered even more clues about our genetic past – that the Yamnaya herders could also be responsible for north-western Europeans being taller than southern Europeans.And while northern Europeans carry more genetic risk for MS, southern Europeans are more likely to develop bipolar disorder, and eastern Europeans more likely to have Alzheimer’s disease and type 2 diabetes.DNA from pre-historic hunter-gatherer people raises the risk of Alzheimer’s, but ancient farmers’ genes are linked to mood disorders, the research explains.It also discovered that humans’ ability to digest milk and other dairy products and survive on a vegetable-heavy diet only emerged about 6,000 years ago. Before that, they were meat-eaters.The research compared DNA from thousands of ancient skeletons found in Eurasia to genetic samples from current-day Europeans. More on this storyDNA sleuths solve mystery of 2,000-year old corpsePublished19 December 2023’Major moment in MS research’ as new trial startsPublished4 April 2023’I was put into care home for elderly at 46’Published27 November 2019Do we finally know the cause of multiple sclerosis?Published14 April 2022Black Death 700 years ago affects your health nowPublished20 October 2022Ancient DNA reveals secrets of Pompeii victimsPublished26 May 2022Related Internet LinksNature paper – Elevated Genetic Risk for Multiple Sclerosis Originated in Steppe Pastoralist PopulationsNature paper – The Selection Landscape and Genetic Legacy of Ancient EurasiansMS Society UK – Information, research and support – MS SocietyThe BBC is not responsible for the content of external sites.