Publisher Health

A new study shows how heteroresistance, a transient resistance common in many bacteria, can act as a precursor to the development of antibiotic resistance. According to researchers at Uppsala University, this is the first time this link has been demonstrated.
“Heteroresistance is common and we have shown that it occurs for at least ten different classes of antibiotics. In a patient carrying heteroresistant bacteria and undergoing treatment with antibiotics, the mortality rate and risk of requiring transfer to an intensive care unit are higher compared to susceptible bacteria. Therefore, if heteroresistance is a stepping stone towards resistance, we need to have much better control of its occurrence and effects,” explains Dan I. Andersson, Professor of Medical Bacteriology at Uppsala University and lead researcher behind the study. Heteroresistance is common in many disease-causing bacteria and can lead to reduced efficacy of antibiotic treatment. This particular type of antibiotic resistance means that the majority of bacteria in a population are susceptible to antibiotics, but there is also a small resistant subgroup that can grow under antibiotic treatment. These resistant bacteria carry more resistance gene copies than the others, which also result in slower growth.
In a comprehensive study published in the journal Nature Communications, researchers at Uppsala University showed in laboratory studies that bacteria can acquire new resistance mutations that restore faster growth. In this way, heteroresistance can act as a springboard and facilitate the evolution towards stable antibiotic resistance. “It is possible that we are wrong, but we have observed the process in the laboratory and there is no reason to believe that it would not also occur in a patient or an animal . This is an important finding in terms of understanding how bacteria become resistant to antibiotics,” notes Andersson.
He believes that this discovery will lead to more clinical studies and increased diagnostics of heteroresistance in microbiological laboratories. Within healthcare, it is important to continue to be restrictive with antibiotics to prevent resistance. “Antibiotics should be used in a smart way, at the right time and not unnecessarily, to prolong the lifetime of our existing antibiotics and to give us time to develop new ones,” continues Andersson.

An “anti-hunger” molecule produced after vigorous exercise is responsible for the moderate weight loss caused by the diabetes medication metformin, according to a new study in mice and humans. The molecule, lac-phe, was discovered by Stanford Medicine researchers in 2022.
The finding, made jointly by researchers at Stanford Medicine and at Harvard Medical School, further cements the critical role the molecule, called lac-phe, plays in metabolism, exercise and appetite. It may pave the way to a new class of weight loss drugs.
“Until now, the way metformin, which is prescribed to control blood sugar levels, also brings about weight loss has been unclear,” said Jonathan Long, PhD, an assistant professor of pathology. “Now we know that it is acting through the same pathway as vigorous exercise to reduce hunger. Understanding how these pathways are controlled may lead to viable strategies to lower body mass and improve health in millions of people.”
Long and Mark Benson, MD, PhD, an assistant professor of medicine at Harvard Medical School, are co-senior authors of the study, which will be published March 18 in Nature Metabolism. Postdoctoral scholar Shuke Xiao, PhD, is the lead author of the study.
Many people with diabetes who are prescribed metformin lose around 2% to 3% of their body weight within the first year of starting the drug. Although this amount of weight loss is modest when compared with the 15% or more often seen by people taking semaglutide drugs such as Ozempic and Wegovy, the discoveries that led to those drugs also grew from observations of relatively minor, but reproducible, weight loss in people taking first-generation versions of the medications.
Post-workout appetite loss
When Long and colleagues at Baylor University discovered lac-phe in 2022, they were on the hunt for small molecules responsible for curtailing hunger after vigorous exercise. What they found was a Frankenbaby of lactate — a byproduct of muscle fatigue — and an amino acid called phenylalanine. They dubbed the hybrid molecule lac-phe and went on to show that it’s not only more abundant after exercise but it also causes people (as well as mice and even racehorses) to feel less hungry immediately after a hard workout.

“There is an intimate connection between lac-phe production and lactate generation,” Long said. “Once we understood this relationship, we started to think about other aspects of lactate metabolism.”
Metformin was an obvious candidate because as it stimulates the breakdown of glucose (thus reducing blood sugar levels) it can trigger the generation of lactate.
The researchers found that obese laboratory mice given metformin had increased levels of lac-phe in their blood. They ate less than their peers and lost about 2 grams of body weight during the nine-day experiment.
Long and his colleagues also analyzed stored blood plasma samples from people with Type 2 diabetes before and 12 weeks after they had begun taking metformin to control their blood sugar. They saw significant increases in the levels of lac-phe in people after metformin compared with their levels before treatment. Finally, 79 participants in a large, multi-ethnic study of atherosclerosis who were also taking metformin had significantly higher levels of lac-phe circulating in their blood than those who were not taking the drug.
“It was nice to confirm our hunch experimentally,” Long said. “The magnitude of effect of metformin on lac-phe production in mice was as great as or greater than what we previously observed with exercise. If you give a mouse metformin at levels comparable to what we prescribe for humans, their lac-phe levels go through the roof and stay high for many hours.”
Further research revealed that lac-phe is made by intestinal epithelial cells in the animals; blocking the ability of mice to make lac-phe erased the appetite suppression and weight loss previously observed.

Finally, a statistical analysis of the people in the atherosclerosis study who lost weight during the several-year study and follow-up period found a meaningful association between metformin use, lac-phe production and weight loss.
“The fact that metformin and sprint exercise affect your body weight through the same pathway is both weird and interesting,” Long said. “And the involvement of the intestinal epithelial cells suggests a layer of gut-to-brain communication that deserves further exploration. Are there other signals involved?”
Long noted that, while semaglutide drugs are injected into the bloodstream, metformin is an oral drug that is already prescribed to millions of people. “These findings suggest there may be a way to optimize oral medications to affect these hunger and energy balance pathways to control body weight, cholesterol and blood pressure. I think what we’re seeing now is just the beginning of new types of weight loss drugs.”
Researchers from Beth Israel Deaconess Medical Center, Harbor-UCLA Medical Center, Cedars-Sinai Medical Center, Baylor College of Medicine, the University of Colorado, the University of Virginia and the Broad Institute contributed to the work.
The study was funded by the National Institutes of Health (grants GM113854, K08HL145095, DK124265, DK136526, HHSN2682015000031, HSN26800004, UM1DK078616 and 1R01HL151855), a Stanford School of Medicine’s Dean’s Fellowship and the American Heart Association.

Researchers at Weill Cornell Medicine have performed the most comprehensive analysis to date of cancer of the ureters or the urine-collection cavities in the kidney, known as upper tract urothelial carcinoma (UTUC). The study, which compared the characteristics of primary and metastatic tumors, provides new insights into the biology of these aggressive cancers and potential ways to treat them.
In the study, which appeared March 18 in Nature Communications, the researchers examined tissue samples from 44 primary and metastatic UTUC tumors. They compared gene mutations and gene activity patterns in these tumors and mapped cell types using a technology that can visualize protein surface markers at the single-cell resolution. A key finding was that the basic molecular characteristics of these UTUC tumors — their molecular subtype — are mostly stable during the evolution from the primary to the metastatic stage. That suggests that oncologists treating UTUC patients may often be able to use analyses of primary tumor samples for molecular subtype-guided treatment of metastases.
“This dataset we generated provides unique insights into UTUC biology and should be an important resource for researchers and clinicians,” said Dr. Juan Miguel Mosquera, a professor of pathology and laboratory medicine and director of research pathology in the Englander Institute for Precision Medicine at Weill Cornell Medicine.
Dr. Mosquera, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, co-led the study with Dr. Bishoy Faltas, an assistant professor of medicine and the Gellert Family-John P. Leonard, M.D. Research Scholar at Weill Cornell Medicine. The study’s first author is Dr. Kentaro O’Hara, who was a postdoctoral research fellow in the Department of Pathology and Laboratory Medicine and in the Englander Institute for Precision Medicine when the study was conducted.
UTUC tumors are rare compared to bladder tumors, accounting for 5 to 10 percent of all urothelial cancers. They are also considered relatively aggressive, and metastatic UTUC tumors are particularly hard to treat successfully. Previously, Dr. Faltas and colleagues illuminated the molecular details of primary UTUC tumors in a widely cited 2019 study. Much less has been known about the characteristics of metastatic tumors that have already spread to distant organs.
Building on this work, the researchers used DNA and RNA sequencing in the current study to map the gene mutations and gene activity patterns in the primary and metastatic samples. With funding from the Cornell Center for Immunology, they also employed a newer technique called Imaging Mass Cytometry. This technique labels key surface proteins on individual cells in the samples, enabling detailed, cell-by-cell identification and spatial mapping of cell types.
“The Imaging Mass Cytometry allowed us for the first time to explore the spatial relationships between tumor cells and other cells such as immune cells that make up the UTUC tumor microenvironment,” said Dr. Mosquera, who is also a pathologist at NewYork-Presbyterian/Weill Cornell Medical Center.

The 2019 study led by Dr. Faltas revealed that primary UTUC tumors usually belong to a particular molecular subtype that also features a relative absence of T cells — suggesting immune suppression in the tumor microenvironment. The new analysis confirmed this pattern and found that metastatic UTUC tumors in a given patient tended to have the same characteristics as the primary tumor.
“Frequently, we are unable to obtain sufficient biopsy tissue from metastatic tumors and have to rely on the molecular analysis of the primary tumor, so it’s important to know that the molecular subtype based on RNA expression is generally stable from the primary to the metastatic stages,” said Dr. Faltas, who is also director of bladder cancer research in the Englander Institute for Precision Medicine and a member of the Meyer Cancer Center at Weill Cornell Medicine, and an oncologist at NewYork-Presbyterian/Weill Cornell Medical Center. “We were able to understand the contributions of different cell types to these molecular subtypes and how they evolve over the cancer’s natural history by analyzing the protein expression of hundreds of thousands of single cells from these tumors.”
The researchers also observed that metastatic UTUC tumor cells had genetic mutations not found in the primary tumors. These differences were much greater in patients undergoing chemotherapy, suggesting that chemotherapy may have induced some mutations.
The study sets the stage for highly personalized, molecularly-guided primary and metastatic UTUC treatment strategies to improve patient outcomes. The single-cell insights gained have the potential to accelerate the development of targeted therapies and immunomodulatory approaches and transform the landscape of UTUC management.
Research reported in this story was supported by the National Cancer Institute of the National Institutes of Health under award number T32CA203702. The research was also supported by funding from the Starr Cancer Consortium.

A team of Northwestern University scientists has developed the first wireless, implantable temperature sensor to detect inflammatory flareups in patients with Crohn’s disease. The approach offers long-term, real-time monitoring and could enable clinicians to act earlier to prevent or limit the permanent damage caused by inflammatory episodes.
More than 1 million Americans have Crohn’s disease, a chronic inflammatory bowel disease that affects the intestines, causes digestive issues and can lead to weight loss, malnutrition and other complications. People with mild cases are treated with oral medications, but these drugs typically fail over time, requiring approximately 70 percent of Crohn’s patients to undergo at least one surgery to remove portions of damaged intestines.
Because heat is indicative of inflammation, the Northwestern scientists tested whether a temperature sensor resting gently against the intestines of mice with Crohn’s disease could provide real-time insight into the progression of the disease, as well as detect episodic flareups. Sure enough, they accomplished both goals in their research, which will be published online March 18 in the journal Nature Biomedical Engineering.
Arun Sharma, whose group led the animal testing, said there is currently no way for clinicians to quickly detect inflammatory events, some of which go unnoticed by patients until the problem becomes so severe that it requires invasive surgery.
“The magnitude of the flareup can be measured with regards to the heat signature,” said Sharma, co-corresponding author on the paper and a research associate professor of urology at Northwestern University Feinberg School of Medicine and of biomedical engineering at McCormick School of Engineering. “Is it so extensive that it’s going to cause tissue damage over time?
“This could be potentially prevented if a clinician has this information readily at hand and can determine what type of therapy can be given to that person at that moment in time, rather than waiting weeks to get a blood analysis, tissue biopsy or fecal analysis. In the meantime, you’re losing valuable minutes regarding tissue damage with this inflammatory event.”
Sharma said this strategy of measuring temperature fluctuations could also be useful for patients with ulcerative colitis, another inflammatory bowel disease, or any condition where there is a prolonged inflammatory response. In their study, the researchers used the wireless sensors to continuously track temperature fluctuations for nearly four months.

Bioelectronics pioneer John Rogers, whose group led the device development, recently published another paper describing an ultrathin, soft implant that measures temperature and perfusion changes as a way to monitor the health of transplanted organs. Once again, the relationship between heat and inflammation was key, as excess inflammation around the transplanted organ can offer an early warning sign that the new organ is being rejected by the patient’s immune system.
“To address Crohn’s disease, we developed an ultraminiaturized, precision temperature sensor with wireless communication capability,” said Rogers, co-corresponding author on the paper. “This tiny, soft device takes the form of a smooth, round capsule that rests within the GI system, without affecting natural physiological processes for long-term recordings. The data show some very unique signatures, in the form of perturbations to natural circadian cycles, known as ultradian rhythms, as early indications of inflammatory responses.”
The scientists discovered that the ultradian temperature rhythms correlate to cyclic variations in stress levels and inflammatory markers in blood, said Surabhi Madhvapathy, co-first author from Rogers group who led the sensor engineering.
“In addition to the short-term variations, we learned over the span of weeks to months, that the average temperature of the intestines decreases,” Madhvapathy said. “This decrease was indicative of the worsening tissue quality over time.”
Following these successful results in mice, the researchers plan to assess the sensor capabilities in human tissues that recreate the inflammatory gut conditions found in Inflammatory Bowel Disease.
Rogers is the Louis Simpson and Kimberly Querrey Professor of Materials Science and Engineering, Biomedical Engineering and Neurological Surgery at McCormick and director of the Querrey Simpson Institute for Bioelectronics, which supported the study. Sharma is director of Pediatric Urological Regenerative Medicine and Surgical Research at Ann & Robert H. Lurie Children’s Hospital of Chicago and the Stanley Manne Children’s Research Institute, and a member of Northwestern’s Simpson Querrey Institute for BioNanotechnology.
Surabhi Madhvapathy of the Rogers group and Matthew Bury of the Sharma group are co-first authors of the paper.

Muscle injuries are common in the active population, and they cause the majority of player leaves in the world of sport. Depending on the severity, recovery of muscle function is quite slow and may require surgery, medication and rehabilitation. Now, a study led by the University of Barcelona reveals a strategy to improve and accelerate recovery from muscle injuries that has potential application in the sports and health sector in general.
This is the first study to provide scientific evidence for faster and more effective recovery from muscle injuries through intermittent exposure to low oxygen availability (hypoxia) in a low-barometric pressure (hypobaric) chamber that simulates high-altitude geographic conditions.
The new approach is important for the recovery of athletes — especially in the competitive elite — but also to mitigate the socio-economic impact of the loss of work productivity caused by these injuries on the active population.
The study, carried out with animal models, has been published in the Journal of Physiology. The authors of the study are the experts Garoa Santoildes, Teresa Pagès, Joan Ramon Torrella and Ginés Viscor, from the Department of Cell Biology, Physiology and Immunology of the UB’s Faculty of Biology.
Why does hypoxia help to regenerate injured muscle?
Hypobaric chambers have long been used to improve physical fitness in high-performance sports (mountaineers, climbers, etc.) and in professional sectors (high-altitude mining, astronomical observation, border control). In hypobaric hypoxia conditions, the body is exposed to a low atmospheric pressure environment in which cells take up less oxygen and generate a physiological response. The beneficial effects of intermittent hypoxia exposure on the body are well described, but its potential applications in biomedicine are still being explored.
“The study indicates that any type of muscle injury could recover more quickly with intermittent exposure to hypobaric hypoxia (simulated altitude), but probably also myotendinous injuries could accelerate their recovery,” says Professor Ginés Viscor, head of the Adaptive Physiology Group: Hypoxia, Exercise and Health at the UB.

In tissues, hypoxia causes local activation of the HIF (hypoxia-induced factor) pathway, which is a sensor of oxygenation levels. “When the amount of oxygen reaching the cells is not sufficient, the HIF protein acts as a switch that activates a series of changes in metabolic pathways to compensate for this deficit,” explains Professor Garoa Santocildes.
Among other pathways, the HIF protein activates the proliferation of more capillary vessels through endothelial growth factor (VEGF), a process that would bring more growth factors, metabolic substrates and oxygen to the muscle level to support the muscle regeneration process after injury.
As Professor Teresa Pagès explains, “in parallel, the HIF protein would also enhance the synthesis of specific proteins, the activity of some enzymes and the efficiency of the mitochondria, which are the cell organelles that supply energy for cellular functions.”
Muscle injuries and therapies: a paradigm shift
In approaching muscle injuries, the classical view of RICE therapy (Rest, Ice, Compression and Elevation) has evolved towards a more holistic and active view, known as PEACE (Protection, Elevation, Avoid NSADs, Compression, Education) and LOVE (Load Management, Optimism, Vascularization, Exercise).
“All this has meant a major paradigm shift in the field of muscle injury recovery,” says Professor Joan Ramon Torrella. “Exposure to hypobaric hypoxia — the expert continues — is fully compatible with this new paradigm, and could even contribute to improving the effects of emerging therapies to accelerate the recovery of injured muscle.”
Therapy based on exposure to low concentrations of oxygen could also help to explore new treatments for pathophysiological injuries. Thus, it would be important to test whether hypoxia can counteract the muscle atrophy typical of sarcopenia — a disease characterised by loss of muscle mass and strength — through the processes involved in muscle recovery (capillary proliferation, more effective oxidative metabolism, etc.).
“In these cases, hypobaric hypoxia intervention would most likely be improved if combined with individualised strength and endurance exercise activities. Even its application in the recovery of patients with persistent COVID-19 syndrome could be improved,” the team concludes.

Venting about a source of anger might feel good in the moment, but it’s not effective at reducing the rage, new research suggests.
Instead, techniques often used to address stress — deep breathing, mindfulness, meditation, yoga or even counting to 10 — have been shown to be more effective at decreasing anger and aggression.
Researchers analyzed over 150 studies involving more than 10,000 participants and found that what really works to reduce anger is lowering physiological arousal — in other words, turning down the heat. Activities that increased arousal overall had no effect on anger, and some activities made it worse — particularly jogging.
“I think it’s really important to bust the myth that if you’re angry you should blow off steam — get it off your chest,” said senior author Brad Bushman, professor of communication at The Ohio State University. “Venting anger might sound like a good idea, but there’s not a shred of scientific evidence to support catharsis theory.
“To reduce anger, it is better to engage in activities that decrease arousal levels,” Bushman said. “Despite what popular wisdom may suggest, even going for a run is not an effective strategy because it increases arousal levels and ends up being counterproductive.”
The study was led by first author Sophie Kjærvik, who completed the review for her Ohio State dissertation. It was published online March 11 in the journal Clinical Psychology Review.
Kjærvik, now a postdoctoral fellow at Virginia Commonwealth University, said the work was inspired in part by the rising popularity of rage rooms that promote smashing things (such as glass, plates and electronics) to work through angry feelings.

“I wanted to debunk the whole theory of expressing anger as a way of coping with it,” she said. “We wanted to show that reducing arousal, and actually the physiological aspect of it, is really important.”
The meta-analytic review was based on 154 studies involving 10,189 participants of different genders, races, ages and cultures. The study selection and analysis were guided by the Schachter-Singer two-factor theory, which assumes that all emotions, including anger, consist of physiological arousal and mental meanings. To get rid of anger, you can work on either of those.
Several previous meta-analytic reviews have focused on changing mental meanings using cognitive behavioral therapy, which works. However, Kjærvik and Bushman said a meta-analytic review on the role of arousal would fill an important gap in understanding how to resolve anger. Their analysis focused on examining both arousal-increasing activities (e.g., hitting a bag, jogging, cycling, swimming) and arousal-decreasing activities (e.g., deep breathing, mindfulness, meditation, yoga).
Results showed that arousal-decreasing activities were effective at fending off the fury in labs and field settings, using digital platforms or in-person instruction, and in group and individual sessions across multiple populations: college students and non-students, people with and without a criminal history, and individuals with and without intellectual disabilities.
Arousal-decreasing activities that were effective at lowering anger across the board included deep breathing, relaxation, mindfulness, meditation, slow flow yoga, progressive muscle relaxation, diaphragmic breathing and taking a timeout.
“It was really interesting to see that progressive muscle relaxation and just relaxation in general might be as effective as approaches such as mindfulness and meditation,” Kjærvik said. “And yoga, which can be more arousing than meditation and mindfulness, is still a way of calming and focusing on your breath that has the similar effect in reducing anger.

“Obviously in today’s society, we’re all dealing with a lot of stress, and we need ways of coping with that, too. Showing that the same strategies that work for stress actually also work for anger is beneficial.”
In contrast, activities that increased arousal were generally ineffective, but also produced a complex range of outcomes. Jogging was the most likely to increase anger, while physical education classes and playing ball sports had an arousal-decreasing effect — suggesting to the researchers that introducing an element of play into physical activity may at least increase positive emotions or counteract negative feelings.
Finding that increasing arousal was not the answer to anger corresponded with previous work led by Bushman that linked venting anger with continued aggression.
“Certain physical activities that increase arousal may be good for your heart, but they’re definitely not the best way to reduce anger,” Bushman said. “It’s really a battle because angry people want to vent, but our research shows that any good feeling we get from venting actually reinforces aggression.”
That being the case, the authors noted that many arousal-decreasing interventions shown to lower the heat of anger are free or inexpensive and easy to access.
“You don’t need to necessarily book an appointment with a cognitive behavioral therapist to deal with anger. You can download an app for free on your phone, or you can find a YouTube video if you need guidance,” Kjærvik said.

A global wave of infections caused by fungi growing drug-resistant has the medical community issuing precautions on how to protect yourself.
Skin contact with microorganisms found in soil or on hard surfaces, such as common shower facilities, or exposure to infected pets, can result in fungal infections known as dermatomycoses. Rashes, itching, burning and skin irritation are among the symptoms.
Epidemiological data published in Microbial Cell indicates that a rise in severe fungal infections has resulted in over 150 million cases annually and almost 1.7 million fatalities globally.
In a recent study published in Pathogens and Immunity, Thomas McCormick and Mahmoud Ghannoum, professors of dermatology at the Case Western Reserve University School of Medicine and affiliated with University Hospitals Cleveland Medical Center, explain how rising antifungal resistance is worsening the problem of invasive fungal infections.
“This is not just an issue that affects individual patients,” McCormick said. “The World Health Organization has recognized it as a widespread threat that has the potential to impact entire healthcare systems if left unchecked.”
Based on their findings, the researchers issued precautions and a “call to action” for the medical community to help protect people from multidrug-resistant fungi — starting with awareness and education.
“Healthcare providers must prioritize the use of diagnostic tests when faced with an unknown fungal infection,” Ghannoum said. “Early detection can make all the difference in improving patient outcomes.”
Patients treated with medications to protect the immune system after cancer and transplant procedures are more vulnerable to fungal infections — making them especially more vulnerable to infections from drug-resistant fungi, the researchers said.

The emergence of multidrug-resistant fungal species, such as Candida auris and Trichophyton indotineae, is especially troubling and requires urgent attention, they reported.
In a studyrecently published in Emerging Infectious Diseases, Ghannoum’s research team and the Centers for Disease Control and Prevention (CDC), detailed a case that demonstrated Trichophyton indotineae, in addition to becoming drug-resistant, was also sexually transmissible.
To address the growing health concern, McCormick and Ghannoum suggest several measures: Increased awareness and education: Raising awareness in the general healthcare setting to obtain a more accurate understanding of the rise of antifungal-resistant infections. Diagnostic Testing: Routine use of diagnostic tests can guide appropriate treatment strategies. Antifungal Susceptibility Testing (AST): Improving insurance reimbursement rates for AST and increasing the number of qualified laboratories with the capacity to perform these tests. Call to Action: Addressing the emerging challenge of antifungal resistance involves concerted efforts from healthcare professionals, researchers, policymakers and the pharmaceutical industry to develop and implement strategies for managing and preventing antifungal resistance.”The ultimate goal of these measures,” Ghannoum said, “is to improve the quality of patient care by ensuring effective treatment and preventing further escalation of the problem.”

Contrary to some claims, laws that criminalize or otherwise punish drug use during pregnancy are more likely to worsen rather than improve health outcomes, according to a paper by researchers at Columbia University Mailman School of Public Health. The study is the first to systematically review the literature on punitive prenatal drug laws — an increasingly common state policy strategy for addressing rising rates of prenatal drug use. The findings are published in the International Journal on Drug Policy.
The authors collected data on the number of states with laws that explicitly allow criminal prosecution, involuntary commitment or that revoke custody rights following allegations of drug use during pregnancy. They then evaluated existing studies testing whether the enactment of such laws was associated health improvements, either for pregnant people themselves or their babies.
Of the 16 studies reviewed, the authors found that contrary to the intent of legislation, most evidence suggested that punitive laws either had no beneficial effects or made things worse. For example, four of the reviewed studies tested whether the adoption of punitive laws was associated with reductions in neonatal drug withdrawal syndrome (NDWS) — a condition that can occur after exposure to opioids and other drugs in utero. Two of the studies found little change while the two others found increased NWDS after a punitive law was adopted.
“There has been considerable concern from within legal, medical and public health communities that punitive prenatal drug policies might increase potential harms. Our findings support this premise and suggest that such approaches constitute ineffective policy,” said lead author Emilie Bruzelius, PhD, a postdoctoral research fellow in the Department of Epidemiology.
“Identifying effective policy strategies to support pregnant people with drug use disorder outside of the criminal-legal system is an important priority,” noted Silvia S. Martins, MD, PhD, professor of Epidemiology at Columbia Mailman School, and senior author.
Co-authors include Melanie S. Askari, Sandhya Kajeepta, Lisa Bates, Seth J. Prins (Columbia University Mailman School of Public Health), Kristen Underhill (Cornell University Law School), and Marian Jarlenski (Pittsburgh School of Public Health).
The study was supported by the National Institutes on Drug Abuse (R01DA045872 and R01DA053745 and T32DA031099).

The use of antipsychotics during pregnancy isn’t linked to childhood neurodevelopmental disorders or learning difficulties, UNSW Sydney-led study shows — giving assurance to those concerned about continuing their medications during pregnancy.
Antipsychotics — a branch of medication designed to treat schizophrenia and bipolar disorder — are important tools for mental health care management. They work by blocking the effect of dopamine, which can help reduce psychotic symptoms such as hallucinations or delusions.
These versatile medications are also widely used for other mental health conditions and developmental disorders, like anxiety, depression, autism spectrum disorder, and insomnia.
But many women and pregnant people using these medications may feel concerned about the potential risks they pose to their unborn baby.
A new international study led by UNSW Sydney, published today in eClinicalMedicine, tracked the long-term risk of a child developing neurodevelopmental disorders and learning difficulties after being exposed to antipsychotics in the womb.
The findings show there’s little to no increased risk of the exposure leading to intellectual disability, poor academic performance in maths and language, or learning, speech and language disorders.
“The findings are really reassuring for both women managing these psychiatric conditions during pregnancy and their providers,” says Dr Claudia Bruno, a pharmacoepidemiologist based at UNSW’s School of Population Health and lead author of the study.

“There’s no increased risk when taking the medication during pregnancy, not only for the specific neurodevelopmental disorders that we looked at, but also ADHD and autism as shown in our team’s previous studies.”
This research is the most comprehensive study on antipsychotics and neurodevelopmental outcomes to date: it pulls together nationwide data from Denmark, Finland, Iceland, Norway, and Sweden into a large sample size of 213,302 children born to mothers with a diagnosed psychiatric condition, 5.5 per cent (11,626) of which were prenatally exposed to antipsychotics.
These five Nordic countries all have similar health and education systems and keep detailed data on birth records, filled prescriptions, and diagnoses from inpatient and outpatient specialist care, as well as antenatal care. The researchers teamed these data with results from the children’s first standardised national school test (similar to Australia’s NAPLAN tests), which happens between the ages of 8-10.
“It’s reassuring that everything points to the same ‘no major indication’ of increased risks overall,” says Scientia Associate Professor Helga Zoega, senior author of the study and pharmacoepidemiologist, also based at UNSW’s School of Population Health.
“The study builds on our team’s previous work that looked at birth outcomes, including serious congenital malformations, where we’ve seen similar null results.
“I think it’s important to get excited about null results because this is essential information for the management of serious mental health conditions in pregnancy. It’s as equally important as finding an increased risk of outcomes.”
A gap that big health data is trying to fix

While this study is part of a growing body of research about medication safety in pregnancy, there’s still a lot left in this field to discover, says A/Prof. Zoega.
“This is a hugely understudied area,” she says. “Unfortunately, we know way too little about medication safety during pregnancy.”
One of the reasons so little is known about medicines and pregnancy is that it’s simply not feasible — or in many cases, ethical — to conduct randomised clinical trials on pregnant women. The potential risks of testing or withholding treatment to the unborn child and mother or pregnant person is often too great.
That’s where harnessing big data can step in — although the research isn’t as simple as looking at the raw data alone.
For example, women treated with antipsychotics during pregnancy were more likely to smoke, have higher BMIs, lower education levels, to be older (35 years or more) and use other medications during pregnancy compared to women who didn’t take antipsychotics during pregnancy — all of which are risk factors that can potentially impact birth outcomes.
These circumstances — called ‘confounding factors’ — are accounted for in observational research using careful study design and complex adjusted risk models to make sure the results show the impact of the medication alone.
“These types of studies are methodologically tricky, and can take a long time to do,” says A/Prof. Zoega. “This study has been in the making for almost 10 years now.
“We already know these women are dealing with psychiatric conditions, and by genetic default, their children would be more likely to have psychiatric or neurodevelopmental outcomes. But we’re focused on the risks and benefits of the medication treatment in pregnancy, so we use methods to make the comparison groups as similar as possible.”
The researchers also strengthened their findings by slicing up the data to take a closer look at whether individual medications, trimesters of exposure, and siblings carried higher risk levels.
While one antipsychotic, chlorpromazine, showed potential increased links to language and speech delays, these findings were based on small sample sizes of 8-15 children, so more research is needed to investigate this potential link.
Other than this anomaly, the results supported the finding that there was little to no increased risk of children prenatally exposed to antipsychotics developing neurodevelopmental disorders or learning difficulties.
Looking ahead
Dr Bruno is currently involved in two related studies on prenatal medication use and pregnancy outcomes. One explores if there is a relationship between the use of antiseizure medications during pregnancy and child school performance, and the other examines whether taking ADHD medication use and discontinuation during pregnancy on child health outcomes.
But she sees many avenues for future research to build on this work, including harnessing more Australian big health data.
“There’s so much to learn about medication safety in pregnancy,” says Dr Bruno. “These women are typically excluded from clinical trials, so there’s a real lack of data or evidence.
“While these results are highly generalisable to women in Australia, we now have real-world linked Australian data that can start contributing to large-scale international studies like this one which we’re very excited for.”
A/Prof. Zoega co-leads an international research collaboration called International Pregnancy Drug Safety Study (InPreSS), which investigates the safety of medication in pregnancy. She says there’s plenty to do in this space.
“Antipsychotics are only one class of medications, and we already know that up to 80 per cent of women use at least one prescription medicine during pregnancy. Most often, there’s little or no guidance on safety.
“There are so many unanswered questions that there’s enough for a lifetime of research.”

The curvature of a surface determines the migration behavior of biological cells. They preferentially move along valleys or grooves while avoiding ridges. These findings with contribution from the Max Planck Institute for Dynamics and Self-Organization (MPI-DS) and the Weizmann Institute of Science gave rise to a model predicting cellular behavior. Such universal principles now allow a better understanding of the migration of immune and cancer cells, paving the way for new treatment options.
Cell migration within the body is a fundamental biological phenomenon. Immune cells constantly scout for pathogens and cancer cells migrate through the body causing metastasis. Inside the body, many surfaces such as tissues, blood vessels, or protrusions have a curved shape. “We were able to demonstrate that these curvatures directly affect the movement pattern of cells,” explains Eberhard Bodenschatz, director at the MPI-DS. The scientists could show experimentally that cells prefer certain curvatures over others, a phenomenon called “curvotaxis.”
To unravel this mechanism, they created a computer model of a vesicle containing active cytoskeletal components used for movement. This structure resembles a biological cell, migrating in the body. “Using this minimal cell model, we systematically explored the curvotaxis mechanism on various curved surfaces,” reports Nir Gov from the Weizmann Institute of Science, Israel. “The model cell shows specific migration patterns, for example where cells move along grooves of a wave-like shape, while avoiding motion along the ridges,” he continues.
This observation gave rise to a new model predicting cell behavior. The predictions of the model were then verified experimentally using several cell types. The scientists thus revealed a universal mechanism for cell motility that applies to many different types of migrating cells. On a convex or tubular structure such as the outside surface of a blood vessel, cells tend to move circumferentially around the shape. In contrast, axial forward or backward movement is preferred on concave structures (such as inside a blood vessel). “Our work highlights how physical principles shape universal behavior, even within the complex world of biology,” concludes Eberhard Bodenschatz.