Seizures in newborns are one of the most frequent acute neurological conditions among infants admitted to neonatal care units. A study published in Developmental Medicine & Child Neurology indicates that newborns experiencing such neonatal seizures face an elevated risk of developing epilepsy.
For the study, investigators analysed data on all children born in Denmark between 1997 and 2018, with the goal of comparing the risk of epilepsy in children with and without neonatal seizures.
Among 1,294,377 children, the researchers identified 1,998 who experienced neonatal seizures. The cumulative risk of epilepsy was 20.4% among children with neonatal seizures compared with 1.15% among children without. This indicates that 1 in 5 newborns with neonatal seizures will develop epilepsy.
Epilepsy was diagnosed before 1 year of age in 11.4% of children with neonatal seizures, in an additional 4.5% between 1 and 5 years, 3.1% between 5 and 10 years, and 1.4% between 10 and 22 years. Stroke, hemorrhage, or structural brain malformations in newborns, as well as low Apgar scores, were associated with the highest risks of developing epilepsy.
“Our study highlights that there are risk factors that may be used to identify infants for tailored follow-up and preventive measures,” said corresponding author Jeanette Tinggaard, MD, PhD, of Copenhagen University Hospital – Rigshospitalet. “Importantly, four out of five neonatal survivors with a history of neonatal seizures did not develop epilepsy, and we suggest future studies to explore a potential genetic predisposition.”
Researchers have found a potential new way to slow the progression of lung fibrosis and other fibrotic diseases by inhibiting the expression or function of Piezo2, a receptor that senses mechanical forces in tissues including stress, strain, and stiffness. The new study in The American Journal of Pathology, published by Elsevier, sheds light on the underlying mechanisms of pulmonary fibrotic diseases and identifies potential new targets and options for therapy to improve patients’ outcomes.
Pulmonary fibrotic diseases are a group of conditions that cause significant morbidity and sometimes mortality. Idiopathic pulmonary fibrosis (IPF) is a devastating progressive fibrotic lung disease with a median survival of 2.9 years from diagnosis. Lung fibrosis results in dramatic mechanical changes including increased stiffness in the tissue that cells can sense and respond to, making it difficult for the lungs to expand and contract properly during breathing.
Piezo channels are a newly discovered receptor that are sensitive to mechanical signals. Since the 2021 Nobel Prize in Medicine was awarded to Dr Ardem Patapoutian for the discovery of Piezo channels in 2010, interest has increased in their role in tissue homeostasis and disease outside of neuronal signalling, however, little has been published on their possible role in fibrotic lung diseases. A group of researchers driven to understand how mechanical forces in lung tissue contribute to and drive pulmonary fibrosis investigated the role of Piezo2 in pulmonary fibrosis using donor tissue from patients with IPF, mouse models of lung fibrosis, cell culture investigation of lung cells (fibroblasts) that create the fibrosis lesions, and by examining publicly available RNAseq datasets from other research groups.
Investigators found that:
Piezo2 is highly expressed in human lung tissue from patients with IPF and in multiple (different) mouse models of lung fibrosis.
Piezo2 is highly expressed in primary human lung fibroblasts in culture, the cells that are believed to play key roles in producing fibrosis in tissues (by proliferating and laying down matrix proteins, creating scar-like features).
Lung fibroblasts grown on stiffer substrates are reprogrammed to be more profibrotic, by proliferating, producing extra matrix proteins, and differentiating to scar-forming myofibroblasts.
Inhibition of Piezo2 with either RNA silencing or a peptide inhibitor, to prevent them from sensing the stiffness of their environment, reduces profibrotic programming.
Lead investigator Patricia J. Sime, MD, Division of Pulmonary Disease and Critical Care Medicine, Virginia Commonwealth University, says, “We are excited to report that this research that suggests inhibiting expression or function of Piezo2 could be a potential new therapeutic route to treating lung fibrosis and other fibrotic diseases. This is especially important as there is an unmet need for additional therapies for fibrotic diseases.”
Despite the introduction of nintedanib and pirfenidone for therapy of some fibrotic lung diseases, pulmonary fibrosis can remain challenging to effectively treat. This is in part because lung cells can be driven to a profibrotic phenotype by multiple pathways that reinforce each other, so that targeting one pathway alone may not be effective to slow or stop disease progression.
First author Margaret A.T. Freeberg, PhD, Division of Pulmonary Disease and Critical Care Medicine, Virginia Commonwealth University, continues, “Some types of lung fibrosis have been very difficult to treat. For example, IPF is a form of pulmonary fibrosis that often progresses. While there have been advances in therapy, the approved medications for IPF can slow, but do not always halt progression. One of the reasons that fibrosis can be difficult to effectively treat may be explained by the multiple profibrotic disease pathways that reinforce each other. Blocking Piezo2 signaling to prevent fibroblast reprogramming represents a new pathway we can target in our fight against fibrosis.”
Dr. Sime concludes, “This research identifies mechanical forces and a new specific target (Piezo2) that we can block to prevent fibrotic reprogramming of some lung cells. We believe this points to Piezo2 as an important new therapeutic target that might (by itself or in combination with other therapies) slow the progression of pulmonary fibrosis in our patients. Many new investigational drugs that target pulmonary fibrosis receive orphan drug designation from the FDA, and this may accelerate development and increase interest from pharmaceutical partners.”
Tiny fragments of plastic have become ubiquitous in our environment and our bodies. Higher exposure to these microplastics, which can be inadvertently consumed or inhaled, is associated with a heightened prevalence of chronic noncommunicable diseases, according to new research being presented at the American College of Cardiology’s Annual Scientific Session (ACC.25).
Researchers said the new findings add to a small but growing body of evidence that microplastic pollution represents an emerging health threat. In terms of its relationship with stroke risk, for example, microplastics concentration was comparable to factors such as minority race and lack of health insurance, according to the results.
“This study provides initial evidence that microplastics exposure has an impact on cardiovascular health, especially chronic, noncommunicable conditions like high blood pressure, diabetes and stroke,” said Sai Rahul Ponnana, MA, a research data scientist at Case Western Reserve School of Medicine in Ohio and the study’s lead author. “When we included 154 different socioeconomic and environmental features in our analysis, we didn’t expect microplastics to rank in the top 10 for predicting chronic noncommunicable disease prevalence.”
Microplastics—defined as fragments of plastic between 1 nanometre and 5 millimetres across—are released as larger pieces of plastic break down. They come from many different sources, such as food and beverage packaging, consumer products and building materials. People can be exposed to microplastics in the water they drink, the food they eat and the air they breathe.
The study examines associations between the concentration of microplastics in bodies of water and the prevalence of various health conditions in communities along the East, West and Gulf Coasts, as well as some lakeshores, in the United States between 2015-2019. While inland areas also contain microplastics pollution, researchers focused on lakes and coastlines because microplastics concentrations are better documented in these areas. They used a dataset covering 555 census tracts from the National Centers for Environmental Information that classified microplastics concentration in seafloor sediments as low (zero to 200 particles per square meter) to very high (over 40 000 particles per square metre).
The researchers assessed rates of high blood pressure, diabetes, stroke and cancer in the same census tracts in 2019 using data from the U.S. Centers for Disease Control and Prevention. They also used a machine learning model to predict the prevalence of these conditions based on patterns in the data and to compare the associations observed with microplastics concentration to linkages with 154 other social and environmental factors such as median household income, employment rate and particulate matter air pollution in the same areas.
The results revealed that microplastics concentration was positively correlated with high blood pressure, diabetes and stroke, while cancer was not consistently linked with microplastics pollution. The results also suggested a dose relationship, in which higher concentrations of microplastic pollution are associated with a higher prevalence of disease. However, researchers said that evidence of an association does not necessarily mean that microplastics are causing these health problems. More studies are required to determine whether there is a causal relationship or if this pollution is occurring alongside another factor that leads to health issues, they said.
Further research is also needed to determine the amount of exposure or the length of time it might take for microplastics exposure to have an impact on health, if a causal relationship exists, according to Ponnana. Nevertheless, based on the available evidence, it is reasonable to believe that microplastics may play some role in health and we must take steps to reduce exposures, he said. While it is not feasible to completely avoid ingesting or inhaling microplastics when they are present in the environment, given how ubiquitous and tiny they are, researchers said the best way to minimise microplastics exposure is to curtail the amount of plastic produced and used, and to ensure proper disposal.
“The environment plays a very important role in our health, especially cardiovascular health,” Ponnana said. “As a result, taking care of our environment means taking care of ourselves.”
In a separate study presented at ACC.25, researchers from a different group reviewed the scientific literature and found that studies showed a strong correlation between microplastics in plaques in the heart’s arteries and the risk of adverse cardiovascular events, suggesting that the presence of microplastics could play a role in the onset or exacerbation of serious heart problems.
Mass General Brigham and MIT investigators have developed a long-acting contraceptive implant that can be delivered through tiny needles to minimise patient discomfort and increase the likelihood of medication use.
Their findings in preclinical models provide the technological basis to develop self-administrable contraceptive shots that could mimic the long-term drug release of surgically implanted devices.
The new approach, which would reduce how often patients need to inject themselves and prove valuable for patients with less access to hospitals and other medical care providers, is described in Nature Chemical Engineering.
“Needle size and liquid viscosity are crucial considerations for commercial translation of injectables,” said senior author Giovanni Traverso, MD, PhD, MBBCH, of the Division of Gastroenterology in the Department of Medicine at Brigham and Women’s Hospital. “Our engineering challenge was finding a way to maximise comfort for patients by using smaller needles, which cause less bruising or bleeding, and to make the viscosity low enough for easy application with the syringe by hand.”
Traditional contraceptive implants are small, flexible rods that are surgically inserted under the skin to slowly deliver drugs over time, removing the hassle of remembering to take a pill. But the surgery required for implants makes them less accessible to some patients.
Traverso’s team developed a new approach to deliver the contraceptive drug levonorgestrel (LNG) through Self-assembling Long-acting Injectable Microcrystals (SLIM). SLIM act like tiny puzzle pieces that, once injected inside the body, undergo solvent exchange to assemble into a single solid implant that slowly releases the drug as the surface erodes. Unlike similar self-administering technologies, the solvent exchange assembly enables delivery by much smaller needles.
The researchers will continue their work to optimize the dosing, duration, and injectability of the SLIM system, including understanding how it performs in the human body. The design could also be applied to other hydrophobic drugs, which make up most new pharmaceuticals. The researchers plan to investigate how different drug properties impact the SLIM system’s effectiveness.
“We anticipate that SLIM could be a new addition to the current suite of family planning options available to women, especially for people in low-resource settings where options for contraception and health care facilities are limited,” said Traverso.
Developed by the University of South Australia in collaboration with the Medical School at Stanford University, this world first formulation uniquely combines limonene (a citrus essential oil) with a lipid-based drug delivery system to treat dry mouth (xerostomia), a common side effect of radiotherapy.
The new formula demonstrated 180-fold better solubility than pure limonene in lab experiments and boosted relative bioavailability by over 4000% compared to pure limonene in pre-clinical trials.
Dry mouth is the most reported side effect following radiotherapy for the treatment of head and neck cancer, affecting up to 70% of patients due to salivary gland damage. It can lead to difficulty speaking and swallowing, significantly reducing quality of life.
Limonene has protective effects on saliva production during radiotherapy, but its poor solubility means high doses are needed to take effect, and these cause indigestion, abdominal discomfort and unpleasant ‘citrus burps’.
Lead researcher, Professor Clive Prestidge says UniSA’s new limonene-lipid combination creates a ‘super-solubilising’ treatment that reduces dry mouth at lower dose and without uncomfortable side effects.
“The therapeutic benefits of limonene are well known. It’s used as an anti-inflammatory, antioxidant, and mood-enhancing agent, and can also improve digestion and gut function. But despite its widespread use, its volatility and poor solubility have limited its development as an oral therapy,” Prof Prestidge says.
“As limonene is an oil, it forms a film on the top of the stomach contents, causing significant stomach pain and discomfort.
“Our novel formulation combines limonene with healthy fats and oils – called lipids – to create a super-solubilising compound that the body can easily absorb with reduced uncomfortable side effects.
“This increases the dispersion of limonene in the stomach, boosts absorption, and controls biodistribution – all while increasing a patient’s saliva production and reducing dry mouth.”
Co-researcher Dr Leah Wright says the formulation has the potential to significantly improve the quality of life for cancer patients and others suffering dry mouth conditions.
“Cancer patients undergoing radiotherapy and other medical treatments regularly experience dry mouth, which not only prevents them from comfortably swallowing, but can also have other negative and potentially life-threatening outcomes,” Dr Wright says.
“While limonene can be ingested directly, it’s not well tolerated, especially by those with dry mouth. Plus, its poor absorption prevents it from effectively reaching the salivary glands – the target site.
“This inventive and highly impactful limonene-lipid formulation could provide a simple, effective oral solution for dry mouth, offering cancer patients long-lasting relief and comfort, improved oral health, and a higher quality of life during a difficult time.”
Clinical trials for the new formula are ongoing, with next steps to be announced soon.
