The material was synthesized through a two-step hydrothermal and phosphorization strategy. Its three-dimensional nanoflower architecture consists of interconnected nanosheets, producing a hierarchical structure with a large specific surface area and abundant accessible active sites. When deposited on the glassy carbon electrode, NiCoP exhibited good electrocatalytic activity toward the oxidation of hydroquinone, catechol and acetaminophen.

The sensor’s calibrated operating ranges extended from 10 to 100,000 micromolar for hydroquinone, from 25 to 19,000 micromolar for catechol and from 25 to 15,000 micromolar for acetaminophen. The hydroquinone range spans four orders of magnitude, while the ranges for catechol and acetaminophen each span approximately three orders of magnitude. The reported detection limit for hydroquinone was the lowest of the three, followed by acetaminophen and then catechol.

These values characterize performance under the optimized conditions used by the researchers; the supplied study summary does not provide the number of replicate measurements or the uncertainty estimates associated with each calibration result. Real-water testing provided the practical validation of the sensor. The investigators quantified hydroquinone, catechol and acetaminophen in water samples and reported satisfactory recoveries for all three analytes, indicating that the electrode could measure the targets in the tested samples as well as under controlled laboratory conditions.

The available evidence does not identify the number or composition of the real-water samples, the full set of tested interferents or the extent to which results would change across other water matrices. The findings support the use of NiCoP as a promising sensing material for environmental monitoring, but they do not establish performance in every environmental setting or establish a clinical use for the sensor.

Subject of Research: Electrochemical sensing of hydroquinone, catechol and acetaminophen with a bimetallic NiCoP nanoflower electrode

Article Title: Bimetallic NiCoP nanoflowers as an efficient electrochemical platform for simultaneous detection of hydroquinone, catechol, and acetaminophen

Article References: Chang, T., Shi, Y., Wu, P., Xie, W., Hao, R., Gao, X., & Lu, W. (2026). Bimetallic NiCoP nanoflowers as an efficient electrochemical platform for simultaneous detection of hydroquinone, catechol, and acetaminophen. Journal of Materials Science, 61(42), 33005-33018. https://doi.org/10.1007/s10853-026-13707-7

Image Credits: AI Generated

DOI: 10.1007/s10853-026-13707-7

Keywords: NiCoP, electrochemical sensor, nanoflowers, glassy carbon electrode, hydroquinone, catechol, acetaminophen, environmental monitoring, bimetallic phosphide, water analysis, Bimetallic, efficient

The compound, named OCLA, was born from a strategy of molecular marriage. The researchers, led by Liu Han, Qiuyue Zhang, and senior authors Sheng Chang and Xin Sun of Jilin Medical University, had previously observed that two natural products, the ginseng saponin (20S,24R)-ocotillol and the antioxidant lipoic acid, acted synergistically to protect liver cells from acetaminophen toxicity. Rather than simply co-administering the pair, they chemically fused them. Using a coupling reaction in dichloromethane catalyzed by EDCI, DMAP, and DCC, the team linked lipoic acid to the ocotillol scaffold and purified seven sulfur-containing derivatives by column chromatography. The final molecule, with the chemical formula C38H64O6S2, was confirmed by high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy, and the synthesis has been granted a Chinese invention patent.

In laboratory dishes, OCLA outperformed its parent compound. When HepG2 liver cells were exposed to a toxic 10 millimolar dose of acetaminophen, an amount calibrated to kill roughly half the cells, pretreatment with OCLA kept significantly more cells alive than pretreatment with ocotillol alone. Encouraged, the team moved to mice. Forty male ICR mice were divided into groups receiving either saline, low-dose OCLA at 16 milligrams per kilogram, high-dose OCLA at 32 milligrams per kilogram, or the known hepatoprotective agent silibinin. After seven days of daily treatment, the animals received a punishing 350 milligrams per kilogram injection of acetaminophen to induce acute liver injury.

The results were striking. Acetaminophen sent serum levels of alanine aminotransferase and aspartate aminotransferase, the classic enzymatic fingerprints of hepatocyte destruction, soaring in untreated animals. Mice pretreated with OCLA, particularly at the higher dose, showed markedly blunted elevations of both enzymes. Under the microscope, livers from acetaminophen-challenged mice displayed severe histopathological damage, while sections from high-dose OCLA-treated animals looked remarkably close to healthy controls. The compound also restored the liver’s glutathione economy: acetaminophen depleted reduced glutathione, the cell’s master antioxidant, and flooded tissue with its oxidized form, but OCLA pretreatment dose-dependently rebuilt the healthy GSH/GSSG ratio, a sign that the cells’ redox defenses had been reinstated.

One of the study’s most commercially and pharmacologically interesting findings came from tracking where OCLA actually goes in the body. Using a sensitive UPLC-MS/MS method, the researchers measured the intact compound in plasma and liver tissue at time points from fifteen minutes to twelve hours after injection. OCLA reached peak concentration within half an hour in both compartments, but its exposure in the liver dwarfed that in the blood: the liver-to-plasma ratio of the area under the concentration-time curve was approximately 6.3, and the compound lingered in hepatic tissue with a mean residence time of 3.22 hours versus only 1.70 hours in plasma. In other words, the molecule behaves as a liver-seeking drug, accumulating exactly where it is needed most.

To understand how OCLA works at the molecular level, the team deployed an integrative multi-omics strategy, sequencing the transcriptomes of control, acetaminophen-exposed, and OCLA-treated livers while simultaneously profiling hepatic metabolites by mass spectrometry. The transcriptomic analysis identified nearly four thousand genes whose expression shifted after acetaminophen exposure, and a comparable number reversed by OCLA. Enrichment analysis flagged pathways tied to inflammation, apoptosis, and anaerobic metabolism, including the IL-17, TNF, MAPK, NF-κB, and HIF-1 signaling cascades. Metabolomics, meanwhile, revealed disturbances in amino acid, retinol, and riboflavin metabolism after acetaminophen, with OCLA restoring profiles linked to linoleic acid and arachidonic acid pathways.

The decisive insight came from intersecting the two datasets. Of nine candidate pathways, only one, the HIF1α signaling pathway, was significantly enriched in both the transcriptomic and metabolomic analyses after OCLA intervention. HIF1α, or hypoxia-inducible factor-1α, is best known as the master switch that cells flip when oxygen runs low, but it has a darker side in injury: it reprograms metabolism toward glycolysis and fans inflammatory fires. In the acetaminophen-injured livers, HIF1α and its downstream glycolytic machinery, including the glucose transporter GLUT1 and the enzymes HK1, HK2, PFKL, PFKFB3, and ENO1, were all markedly upregulated. OCLA pretreatment pulled the entire program back down to baseline, and with it suppressed the inflammatory cytokines IL-6 and TNF-α and apoptosis-related proteins such as BAX, p21, and the inflammatory mediator p65.

The team then asked whether OCLA touches HIF1α directly. Molecular docking against the HIF1α structure yielded a favorable binding score, and a cellular thermal shift assay provided experimental confirmation: when HepG2 cells were heated across a gradient from 40 to 58 degrees Celsius, HIF1α protein in OCLA-treated cells remained stable at temperatures where the untreated protein denatured, a hallmark of direct drug-target engagement. As an independent check, the researchers treated injured liver cells with cyclo, a known HIF1α inhibitor, and saw the same dampening of inflammatory and apoptotic markers, reinforcing the conclusion that HIF1α sits at the center of the protective mechanism.

The study is not without caveats, and the authors are candid about them. Every in vivo experiment used intraperitoneal injection and a preventive regimen in which OCLA was given for seven days before the acetaminophen challenge, so the compound’s oral bioavailability, its full absorption, distribution, metabolism, and excretion profile, and, crucially, its ability to rescue livers after an overdose has already occurred all remain open questions. Endogenous esterases could partially hydrolyze the molecule in liver tissue, meaning some of the observed effect might involve breakdown products. Future head-to-head studies against N-acetylcysteine in a therapeutic setting will be needed to establish clinical relevance for established intoxication.

Even with those limitations, the work offers a compelling proof of concept on two fronts. It validates HIF1α-mediated glycolytic reprogramming as a druggable node in acetaminophen liver injury, a mechanism that extends a growing body of research linking this transcription factor to inflammation and metabolic dysfunction in diseases from kidney fibrosis to cancer. And it demonstrates a rational design pipeline in which two synergistic natural products are fused into a single, liver-accumulating, patent-protected molecule whose target is revealed not by guesswork but by converging transcriptomic, metabolomic, docking, and biophysical evidence. If follow-up studies confirm that OCLA or its successors can protect the liver after overdose rather than only before, a ginseng-inspired synthesis could someday give emergency physicians a much-needed second weapon against the world’s most common cause of drug-induced liver failure.

Subject of Research: A novel ginsenoside derivative, OCLA, protects against acetaminophen-induced liver injury by targeting HIF1α-mediated glycolytic metabolism

Article Title: Design, synthesis of a novel ginsenoside derivative and its protection against acetaminophen induced liver injury via suppressing HIF1α-mediated glycolytic metabolism

Article References: Han, L., Zhang, Q., Shang, W., Wang, X., Han, Y., Wang, Q., Ren, H., Ma, X., Gao, L., Chang, S., & Sun, X. (2026). Design, synthesis of a novel ginsenoside derivative and its protection against acetaminophen induced liver injury via suppressing HIF1α-mediated glycolytic metabolism. Frontiers in Pharmacology, 17, Article 1942215. https://doi.org/10.3389/fphar.2026.1942215

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1942215

Keywords: acetaminophen, drug-induced liver injury, OCLA, ginsenoside, ocotillol, lipoic acid, HIF1α, glycolysis, hepatoprotection, multi-omics, molecular docking, pharmacokinetics

The device is the work of Sina Khazaee Nejad, Maral Mousavi, and colleagues, who set out to merge two functions that are normally separated in diagnostic testing: sample collection and analysis. Traditional saliva testing typically involves a swab or absorbent pad that soaks up fluid from the mouth, after which the sample must be packaged, transported, and processed on benchtop instruments elsewhere. That separation adds time, cost, and opportunities for error, and it can be particularly awkward when the patient is a child. By contrast, Lollylab is designed to do everything at once. The candy coating stimulates saliva production, the stem channels the fluid to an integrated sensor, and the sensor reports the result on the spot. As Nejad, the first author of the paper, explained, turning a familiar object like a lollipop into both a collection device and a sensor means the sample can be gathered and measured directly at the point of care.

The clinical motivation behind the project is rooted in the pharmacology of acetaminophen itself. The compound, known in some countries as paracetamol, is an ingredient in a vast array of over-the-counter products, including standalone pain relievers and combination cold and flu remedies. Because it is so easy to obtain and appears in so many formulations, unintentional overdose is a persistent safety concern. Taking more than the maximum recommended dose can cause serious side effects, most notably liver damage. The risk is especially acute for children, who can experience harm at lower levels of the medication than adults and who may be exposed accidentally when caregivers underestimate how much of the drug is already present in combination products. A quick, noninvasive way to check how much of the drug is circulating in a patient’s body could therefore be a meaningful safeguard.

Saliva turns out to be a surprisingly good window into that circulating level. Previous work has shown that acetaminophen concentrations in saliva closely reflect those in blood, which means the drug’s pharmacokinetics can be tracked without drawing blood. That correlation is what made the researchers consider saliva as a simple, noninvasive monitoring medium. The challenge was not so much detecting the drug in saliva as making the entire process pleasant enough that patients, and especially young ones, would cooperate willingly. Blood draws are invasive and frightening for many children, and even standard saliva swabs can trigger gagging or discomfort. The insight behind Lollylab is that the collection step could be reframed as a treat rather than a procedure.

The design lineage of the device traces back to an earlier invention called CandyCollect, a lollipop-like sampling system developed to replace throat swabs for diagnostic testing. Mousavi says that system inspired the team, but CandyCollect specimens still need to be analyzed elsewhere, so the researchers wanted to go a step further and create what they describe as a miniature laboratory-on-a-lollipop. Where CandyCollect demonstrated that a candy-based device could harvest useful biological samples at home, Lollylab embeds the analytical chemistry into the lollipop itself, closing the loop between collection and measurement.

Mechanically, the device is elegantly simple. It is built from two plastic pieces, each with a round end and a thinner stem, that snap together. Holes at the top allow saliva to enter the interior of the candy head. The upper portion of the device is coated with a red, peach-flavored edible candy shell, which serves a dual purpose: it makes the object genuinely appealing to lick, and the act of licking stimulates the flow of saliva that the test requires. Importantly, the researchers confirmed that the candy coating did not interfere with the measurements, so the flavoring is a genuine functional element rather than a cosmetic afterthought.

Once saliva enters the device, it flows through the lollipop’s stem, which is lined with glass fiber paper, toward a sensor at the bottom. That sensor is made of graphene, a single-atom-thick form of carbon prized in electrochemical sensing for its high conductivity and large surface area. The graphene electrode measures acetaminophen levels as changes in electrical current, a readout strategy common in electroanalysis: the drug oxidizes at the electrode surface, and the magnitude of the resulting current is proportional to its concentration in the sample. Because the electronics can be miniaturized, the entire analytical pathway fits within the stem of a lollipop-sized object. In laboratory testing, the prototype successfully detected acetaminophen in both artificial saliva and real human saliva, demonstrating that the candy matrix and the complex chemistry of real oral fluid did not block the electrochemical signal.

The proof-of-concept study put the device into the hands of actual users. Six adults used Lollylab before taking a standard adult dose of acetaminophen, 650 milligrams, and then again an hour after taking it, a timeframe chosen to capture the period when the drug reaches measurable levels in the body. The device reliably measured the drug in the participants’ saliva in less than two minutes, confirming that the sampling-to-signal pipeline works on realistic post-dose saliva rather than only on spiked laboratory samples. Just as significant for the researchers, the participants said the device was easy to use and more comfortable than typical saliva swabs, an early signal that the candy-based format may overcome the compliance problems that plague conventional oral fluid collection.

For Nejad, the central message of the work is that diagnostic testing can be made much easier and more comfortable, especially for children. That framing positions Lollylab not merely as a faster acetaminophen meter but as a template for a different philosophy of diagnostics, one in which the sample collection experience is designed around the patient rather than the laboratory. A device that a child is happy to put in their mouth removes a major barrier to repeated testing, which matters for monitoring because a single measurement captures only one moment in the drug’s journey through the body. Repeated, low-friction measurements could give clinicians a fuller picture of how a patient is absorbing and clearing a medication.

The team’s roadmap extends well beyond acetaminophen. Next, the researchers plan to validate Lollylab’s acetaminophen measurements with more participants, including children, the population for whom the device’s comfort advantages matter most. They also intend to develop the platform to detect other substances in saliva, such as naturally occurring stress markers, and their longer-term goal, as Nejad describes it, is to create a multi-assay platform capable of measuring several biomarkers, which could then be evaluated alongside acetaminophen in larger clinical studies. The work was funded in part by a 3M Nontenured Faculty Award, Women in Science and Engineering at the University of Southern California, and the President’s Sustainability Research Award, and some of the authors have filed a provisional patent based on the device. If subsequent validation succeeds, the humble lollipop may become a serious instrument of point-of-care medicine, transforming a routine dose check from a clinical chore into something a patient might actually look forward to.

Subject of Research: A lollipop-shaped saliva collection and graphene electrochemical sensing device for point-of-care monitoring of acetaminophen levels

Article Title: Candy-coated Lollylab checks saliva for medication

Article References: Candy-coated Lollylab checks saliva for medication. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: Lollylab, acetaminophen, saliva diagnostics, graphene sensor, point-of-care testing, pediatric safety, drug monitoring, electrochemical sensing, CandyCollect, ACS Sensors, noninvasive testing, biomarkers

The study, published in the Journal of Perinatology by a team led by Sharada H. Gowda of Indiana University and Riley Children’s Hospital, gathered written PDA management guidelines from hospitals belonging to the Children’s Hospitals Neonatal Consortium, a network of 44 quaternary-level neonatal intensive care units in the United States and Canada. Between November 2023 and February 2024, the researchers emailed designated representatives at every member center, asking whether their institution maintained a formal written guideline for managing the condition in premature infants and requesting a copy if one existed. Thirty-eight of the 44 centers responded, an 86 percent response rate, and 25 of those, roughly two-thirds, provided written protocols for analysis.

What the researchers found was a field united by a broad philosophy but divided on nearly every practical detail. Most guidelines described a stepwise approach that begins with expectant, or watchful, management, escalates to drug therapy when the ductus becomes hemodynamically significant, and reserves procedural closure for infants who fail medical treatment. Yet beneath that shared skeleton, the specifics varied dramatically. Screening strategies, diagnostic thresholds, drug choices, dosing schedules, feeding policies, and the timing of interventions all differed from center to center, sometimes in striking ways.

The diagnosis itself is the first fault line. Hemodynamically significant PDA, abbreviated hsPDA, refers to a ductal shunt substantial enough to disturb the infant’s circulation, potentially stealing blood from the gut and lungs and contributing to serious complications such as bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, and prolonged intensive care stays. Because clinical signs such as a heart murmur, bounding pulses, or worsening respiratory status are notoriously nonspecific, objective echocardiographic assessment has become the cornerstone of diagnosis. In the survey, 88 percent of guidelines specified echocardiographic criteria, most commonly ductal diameter, the left atrium-to-aorta ratio, shortened isovolumic relaxation time, and flow reversal in the descending aorta. Less frequently cited markers included flow reversal in the celiac trunk or middle cerebral artery, parameters that reflect more severe systemic hypoperfusion.

Clinical criteria appeared in 80 percent of the guidelines, and respiratory support requirements dominated that category. Among centers that referenced breathing support, 42 percent cited escalating respiratory needs, 37 percent required at least noninvasive ventilation or nasal continuous positive airway pressure, and a small number demanded intubation or used a quantitative respiratory severity score. Other clinical triggers included pulmonary edema, cardiomegaly, pulmonary hemorrhage, widened pulse pressure, and a hyperdynamic precordium, the pounding chest sensation produced by a large shunt. Only 12 percent of centers, however, employed a formal clinical scoring system, a strikingly low figure given growing evidence that composite scores may predict outcomes better than any single parameter.

Screening practices revealed similar heterogeneity. Ninety-two percent of guidelines described risk-based or symptom-based screening for the condition, but the timing of the first echocardiogram ranged from within 36 hours of birth for the most immature infants at some centers to delayed evaluation in the second week of life at others. Some centers screened purely on gestational age, some purely on symptoms, and about a third used a combination of the two. This scatter mirrors the unsettled evidence base: randomized trials and meta-analyses have repeatedly failed to show a clear benefit of routine early treatment compared with expectant management, leaving each institution to chart its own course through the ambiguity.

When treatment is warranted, ibuprofen has emerged as the workhorse drug, recommended as first-line pharmacotherapy by more centers than any alternative. Indomethacin, the traditional cyclooxygenase inhibitor that dominated PDA therapy for decades, has been displaced, while intravenous acetaminophen, increasingly popular at the bedside, remains underrepresented in formal protocols, a discrepancy the authors interpret as evidence that written guidelines lag behind evolving clinician preferences. A quarter of centers recommended prophylactic therapy for the highest-risk infants, such as those born before 25 to 26 weeks without antenatal steroid exposure, with some using indomethacin and others administering acetaminophen at 15 milligrams per kilogram every six hours for twelve doses. The number of treatment courses allowed also varied widely, from a single course at one center to as many as four at others.

Feeding practices during therapy, long a source of anxiety because of theoretical concerns about gut injury, showed a reassuring convergence. Not a single guideline recommended holding feeds entirely during pharmacotherapy, and most centers either allowed full feeding, restricted volume modestly, or permitted trophic feeds. This aligns with accumulating evidence that withholding feeds prolongs the time needed to reach full nutrition without reducing gastrointestinal complications, and that feed interruption may even explain some of the poor outcomes previously attributed to the drugs themselves. On the expectant side, centers that described conservative management uniformly recommended fluid restriction of 120 to 140 milliliters per kilogram per day, with most also endorsing higher breathing pressures, diuretics, and higher hemoglobin targets, while explicitly encouraging rather than restricting nutrition.

Perhaps the most consequential trend captured by the survey is the rise of transcatheter closure. Ninety-two percent of guidelines addressed device-based closure, and 83 percent of those recommended a course of pharmacotherapy before resorting to the catheter procedure. Minimum weight thresholds for device closure ranged from 650 to 1,800 grams, and several centers specified waiting until 14 or 21 days of life. Surgical ligation, once the default definitive treatment, appeared in only 48 percent of guidelines and was frequently reserved for infants too small for the catheter approach. The shift reflects the maturation of minimally invasive occluder devices and a growing recognition that surgical ligation carries risks of its own, including vocal cord paralysis and the controversial post-ligation syndrome, for which, remarkably, only one center in the entire consortium offered written guidance.

The authors are careful to note the study’s limits: written guidelines may not match what actually happens at the bedside, the survey captured no patient outcomes, and the findings come exclusively from large referral centers that may not represent community hospitals. The timing also matters, since the data collection preceded several landmark trials, including BeNeDuctus, BabyOSCAR, and the Neonatal Research Network PDA Randomized Clinical Trial, each of which concluded that conservative management performs as well as or better than drug treatment, though all were constrained by early termination, treatment crossover, and the exclusion of the sickest infants. Still, the picture that emerges is of a specialty in transition, holding onto a common stepwise framework while awaiting the evidence needed to settle its deepest disagreements. For the smallest patients, whose lives often hinge on decisions made within hours of birth, the path from a leaking vessel in the heart to a healed one still depends, to a remarkable degree, on which hospital door they enter first.

Subject of Research: Variation in diagnosis and management of hemodynamically significant patent ductus arteriosus across neonatal intensive care units

Article Title: Variations in diagnosis and management of hemodynamically significant patent ductus arteriosus across neonatal intensive care units in the Children’s Hospitals Neonatal Consortium

Article References: Gowda, S. H., Levy, P. T., Hamrick, S., Keene, S., Sen, S., Rajgarhia, A., Rao, R., Ball, M. K., Weems, M. F., & on behalf of CHNC Cardiac Focus Group (2026). Variations in diagnosis and management of hemodynamically significant patent ductus arteriosus across neonatal intensive care units in the Children’s Hospitals Neonatal Consortium. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02910-8

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02910-8

Keywords: patent ductus arteriosus, preterm infants, neonatal intensive care, echocardiography, ibuprofen, acetaminophen, transcatheter closure, surgical ligation, clinical guidelines, Children's Hospitals Neonatal Consortium, hsPDA, neonatology

The ductus arteriosus is a fetal shortcut that connects the pulmonary artery to the aorta, allowing blood to bypass the fluid-filled, non-functioning lungs before birth. In most babies, the vessel seals itself within the first days of life. In premature infants, however, closure often fails. The problem is remarkably common: an estimated 66 to 79 percent of neonates born weighing less than 1000 grams still have a patent ductus at seven days of age. Whether that open vessel is merely a lingering remnant or a genuine threat to fragile organs depends on its hemodynamic significance, meaning the degree to which it steals blood from the systemic circulation and floods the lungs. And that, precisely, is where consensus collapses, because no universally accepted standard exists for defining when a ductus has crossed the line from benign to dangerous.

The new study, led by Paige E. Condit and John S. Hokanson of the University of Wisconsin-Madison, set out to map this contested terrain. Between February and April 2024, the researchers distributed an anonymous Qualtrics survey to members of the American Academy of Pediatrics Section on Neonatal-Perinatal Medicine, the Section on Cardiology and Cardiac Surgery, and the Pediheart.net online community. Roughly 504 providers began the survey and 422 completed it, yielding an overall response rate of about 8 percent. The analytic sample included 315 neonatologists and 107 pediatric cardiologists. Importantly, the neonatology group was stratified by whether the respondent’s institution offered in-house catheter-based ductal closure, a proxy for the highest-acuity Level IV neonatal intensive care units, allowing the investigators to probe whether access to advanced procedural capability shapes clinical judgment.

The headline result is a portrait of deep disagreement over echocardiography, the ultrasound technique on which virtually all modern ductal assessment rests. Respondents were asked to rank the clinical utility of 14 echocardiographic parameters on a three-point importance scale; the analysis focused on the nine parameters most commonly included in published scores and guidelines. Of those nine, the specialists agreed on the importance of only two: retrograde flow in the post-ductal aorta and the diameter of the ductus itself. For the remaining seven, including measures of left ventricular output, left atrial to aortic root ratio, and end-diastolic flow velocity in the branch pulmonary arteries, neonatologists and cardiologists assigned statistically different levels of both familiarity and importance. The largest familiarity gaps appeared for pulmonary artery end-diastolic flow velocity and left ventricular outflow, with effect sizes reaching the large range, a signal that the two specialties are not merely quibbling over fine points but diverging on fundamental diagnostic building blocks.

One intriguing pattern emerged from the stratification: neonatologists working at centers with in-house catheter closure capability tended to answer more like cardiologists than did their colleagues at centers without such programs. The authors attribute this to daily collaboration, noting that proximity to interventional cardiology likely exposes neonatologists to the same imaging vocabulary and interpretive habits. The implication is sobering for the field, because it suggests that even within a single specialty, the perceived meaning of an echocardiographic image may depend less on the image itself than on the institutional culture surrounding it. When two subspecialties disagree on which markers define hemodynamic significance, confusion can ripple through clinical handoffs, treatment decisions, and even the design of research studies, since cardiology-led and neonatology-led investigations may prioritize different aspects of ductal evaluation.

Formal scoring systems, which were developed precisely to resolve this ambiguity, remain strikingly underused. Only a minority of respondents reported employing any echocardiographic or clinical scoring system, with routine use ranging from 7.8 percent among neonatologists without catheter programs to 19.4 percent among those with them. The survey was conducted before the American Academy of Pediatrics released its recent clinical practice guideline, which recommends a combined echocardiographic and clinical approach with specific criteria required from each domain, so adoption may shift. But the authors point to a deeper problem: several validated scores exist, including the El-Khuffash score, which incorporates gestational age, ductal diameter, flow velocity, and left ventricular measures and has shown strong prediction of chronic lung disease or death with an area under the curve of 0.92, yet none has been proven in a randomized trial to improve outcomes when used to guide treatment compared with clinical judgment alone. A small feasibility trial of score-guided therapy did not demonstrate a statistically significant benefit, and the Iowa score’s reported reductions in severe bronchopulmonary dysplasia cannot be cleanly attributed to the score because the protocol bundled early screening echocardiography and other care changes together.

The survey also documented a quiet revolution in treatment delivery. Medical therapy was available to 99 percent of respondents, but prophylactic treatment was rare, reported by just 12.3 percent. Among first-line agents, acetaminophen narrowly led at 32.8 percent, followed by ibuprofen at 30.5 percent and the older indomethacin at 23.9 percent, with significant differences between specialties, partly because nearly half of cardiologists reported not making these pharmacologic recommendations at all. Most providers, 59 percent, said they would attempt medication-based closure twice before recommending a procedure, while about a quarter would try three times. When it came to procedural closure, the landscape has flipped: 72.1 percent of respondents said they rarely recommend surgical ligation, while catheter-based occlusion, recommended often by 65.1 percent of cardiologists and 48.1 percent of catheter-equipped neonatologists, has been rapidly adopted. An overwhelming 89 percent of respondents named the Amplatzer Piccolo device as their preferred occlusion device, a preference that did not differ by specialty. This shift follows studies suggesting better respiratory outcomes and lower mortality with transcatheter closure compared with surgery, even though no definitive trial has yet shown transcatheter closure to be superior to expectant management.

Screening practices added another layer of variation. Only 13.5 percent of respondents reported that their facility used routine screening echocardiograms for ductal evaluation. Among those who did, the average timing was 28.3 weeks’ gestation, but the spread was wide: neonatologists with in-house catheter programs screened earliest at a mean of 27.5 weeks, those without screened at 27.8 weeks, and cardiologists reported a mean of 31.0 weeks, a statistically significant difference with a medium effect size. The authors caution, however, that the question about screening echocardiography may have been interpreted differently across specialties, a reminder that survey-based comparisons of practice carry their own measurement hazards.

Indeed, the study’s limitations deserve as much attention as its findings. With an 8 percent response rate, non-response bias is a real concern; respondents may be more interested or experienced in ductal management than their silent colleagues, so the results reflect an engaged subset rather than a nationally representative sample. The survey did not capture practice setting, patient volume, or how often respondents actually manage hsPDA, all of which could confound the specialty comparisons. Membership overlap between the cardiology organizations means some cardiologists may have received duplicate invitations and potentially responded more than once, and multiple responses from the same institution could have skewed resource-availability estimates. The survey instrument lacked formal psychometric validation, multiple statistical comparisons were performed without correction for multiplicity, and respondents averaged 18 years in practice, which may not capture the habits of newer generations of clinicians.

Still, the big picture is hard to escape. A vessel present in most extremely premature infants is being diagnosed, scored, medicated, and closed in wildly different ways across the country, by specialists who cannot agree on which ultrasound measurements matter most. The authors call for studies that correlate echocardiographic findings with clinical outcomes and with hemodynamic data from cardiac catheterization, the gold standard of direct measurement, to finally anchor the definition of hemodynamic significance in physiology rather than tradition. Until that evidence arrives, the treatment of the premature ductus will remain what this survey reveals it to be: a high-stakes judgment call, made at the bedside of the smallest patients, under rules that two specialties are still writing separately.

Subject of Research: Diagnosis and management of hemodynamically significant patent ductus arteriosus in premature infants

Article Title: Current practices in the management of hemodynamically significant patent ductus arteriosus

Article References: Condit, P. E., Erdmann, A. A., Zhang, X., Ndukwe, E., Fernandez, J., & Hokanson, J. S. (2026). Current practices in the management of hemodynamically significant patent ductus arteriosus. Journal of Perinatology. https://doi.org/10.1038/s41372-026-02914-4

Image Credits: AI Generated

DOI: 10.1038/s41372-026-02914-4

Keywords: patent ductus arteriosus, premature infants, echocardiography, neonatology, pediatric cardiology, catheter closure, scoring systems, survey, neonatal intensive care, acetaminophen, ibuprofen, surgical ligation

The study, titled Acetaminophen Use During Pregnancy and Autism on TikTok: Disproportionate Exposure to Misinformation in a Content Analysis, was conducted by researchers including Shivani Srivastava, a medical student at Rutgers School of Medicine, with study author Katherine Poole scheduled to present the work at the meeting. The research team set out to understand exactly what information pregnant patients and their families were being exposed to online after seeing questions about Tylenol safety arise in their own clinics. Their results paint a striking picture of how algorithmic amplification can distort the public information environment around a sensitive reproductive health topic, even when a substantial share of the available content is scientifically sound.

TikTok has become a primary source of health information for adolescents and young adults, a population that is particularly vulnerable when algorithmic recommendation systems accelerate the spread of medical misinformation. Because the platform serves large numbers of people of reproductive age, misinformation about prenatal exposures poses direct risks to prenatal health decision-making. In September 2025, public attention to a proposed association between prenatal acetaminophen exposure and autism spectrum disorder, despite the absence of causal evidence, triggered a rapid surge of TikTok content on the topic. The researchers seized on this moment as a natural experiment in how health controversy unfolds on a recommendation-driven platform.

Methodologically, the team conducted a cross-sectional content analysis of 53 TikTok videos posted between September and November 2025, immediately after the FDA announcement. The videos were identified using the search terms tylenol autism, acetaminophen autism, and paracetamol autism, along with the hashtag tylenol, and the study received institutional review board approval under protocol Pro2026000574. Two reviewers independently coded each video for misinformation status, creator type, educational quality as measured by the validated Global Quality Scale, thematic framing, and engagement metrics. Inter-rater reliability for the misinformation classification was substantial, with a Cohen’s kappa of 0.86, indicating strong agreement between the independent coders.

The statistical analysis was rigorous for a study of this scale. Group differences were assessed using Fisher’s exact test and Kruskal-Wallis tests, and independent predictors of misinformation were identified using Firth penalized logistic regression, a method well suited to small samples and rare outcomes. All analyses were performed in R version 4.5.3. The headline numbers were sobering: of the 53 videos, 52.8 percent contained evidence-consistent information, 28.3 percent contained outright misinformation, and 18.9 percent were classified as mixed or uncertain. In other words, the majority of content was accurate, yet the misinformation punched far above its weight in reach.

That asymmetry between volume and visibility is the study’s most consequential finding. Despite comprising only 28.3 percent of the videos analyzed, misinformation accounted for 52.4 percent of total views across the 28.13 million total views recorded for all content examined. A single misinformation video reached 10.3 million views, representing 36.6 percent of all exposure across the analyzed videos. As Srivastava explained, the misinformation videos, despite being a smaller portion of the overall available subject content, accounted for over half of the total views of all the content the team examined. The results, she said, indicate that TikTok’s algorithm amplified low-quality, conspiracy-framed videos containing misinformation on a very sensitive health topic and allowed them to spread far wider than evidence-based videos explaining the lack of causal evidence between prenatal acetaminophen exposure and autism.

Who was creating the misinformation mattered as much as how widely it traveled. Health professionals in the sample produced exclusively evidence-consistent content, while influencers accounted for 73.3 percent of all misinformation videos, a difference the authors report as statistically significant. Nearly three-quarters of the videos containing misinformation were therefore created by influencers rather than medical professionals. The quality gap was equally pronounced: misinformation videos scored significantly lower on educational quality than evidence-consistent videos, with a mean Global Quality Scale score of 1.73 compared with 4.18. Misinformation videos were also far more likely to employ conspiracy framing, present in 46.7 percent of them, and pharmaceutical distrust themes, present in 53.3 percent.

The regression analysis added an important nuance to the creator story. When the researchers adjusted for other factors, lower educational quality and conspiracy framing each remained independently associated with misinformation, with p values of less than 0.001 and 0.012 respectively, but creator type was no longer independently significant after adjustment. This suggests that the defining features of misinformation on the platform are not simply who makes the content but what the content looks like: videos that are poorly sourced, sensational, and framed around conspiracy narratives are the ones that both constitute misinformation and attract algorithmic amplification. The study’s figures visualize this pattern, with one bubble plot mapping each video’s Global Quality Scale score against its view count on a logarithmic scale, and a second plotting the odds ratios and 95 percent confidence intervals from the Firth penalized logistic regression model.

The clinical implications are direct. As more people turn to social media, and especially TikTok, for medical advice, the researchers argue that it becomes increasingly important for pediatricians to proactively address misinformation with patients and their families, including patients of reproductive age who may be weighing acetaminophen use during pregnancy. Srivastava noted that the project grew out of frontline experience: after seeing pregnant patients in their own clinics question whether it was safe to take Tylenol during pregnancy, the team wanted to understand what information those patients were being exposed to online. The findings, she said, reveal how important it is for medical institutions to be part of the conversations on social media by sharing accurate, engaging content that reaches patients where they are, rather than ceding that space entirely to untrained creators.

Beyond the exam room, the authors conclude that broader solutions will require platform-level content moderation and coordinated public health responses to counter misinformation on platforms widely used by adolescents and young adults. The acetaminophen episode illustrates a structural problem that no single clinician can solve: an evidence base showing no causal link between prenatal acetaminophen exposure and autism coexisted with a recommendation algorithm that rewarded the most conspiratorial and lowest-quality content on the subject with the largest audiences. Until the incentives of algorithmic distribution change, the study suggests, accurate health information will continue to compete at a disadvantage against content engineered for outrage, and medical institutions will need to meet patients on the same platforms with content that is both scientifically sound and genuinely engaging.

Subject of Research: TikTok misinformation about prenatal acetaminophen exposure and autism following the FDA's 2025 label change announcement

Article Title: TikTok misinformation content on acetaminophen and autism surged after presidential announcement

Article References: TikTok misinformation content on acetaminophen and autism surged after presidential announcement. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: TikTok, acetaminophen, autism, misinformation, pregnancy, FDA, social media, pediatrics, public health, algorithmic amplification, influencers, content analysis

The research team, led by Jessica Visone, a second-year medical student at Rutgers New Jersey Medical School, with contributions from Kathryn Whitehill, MD, and medical students Shivani Srivastava and Katherine Poole, conducted a cross-sectional audit of 65 public Instagram accounts between September 22 and November 15, 2025. The sample was deliberately constructed to capture the organizations families trust most: the top children’s hospitals for pediatric and adolescent behavioral health, professional medical societies, and the state health departments serving the largest pediatric populations in the country. The starting date was not arbitrary. On September 22, 2025, the White House issued messaging linking prenatal acetaminophen use to autism, a claim made despite the absence of causal evidence, and the resulting controversy spread rapidly across platforms. The researchers used the American Academy of Pediatrics as a benchmark, measuring time to first relevant post, the proportion of controversy-related content, and the quality of that content.

The headline finding was stark. Only 14 of the 65 institutions, or 21.5 percent, posted any content addressing the controversy or correcting the false claims about acetaminophen and autism. The American Academy of Pediatrics was the clear outlier in responsiveness: it posted on Day 1 of the study window and published 10 relevant posts across the period. At the other end of the spectrum, none of the state health departments posted any relevant content at all, and children’s hospitals that did respond lagged as long as 51 days behind the AAP’s first post. In practical terms, that means a family scrolling Instagram in late September could have encountered viral claims connecting a common fever and pain medication to autism, with no corrective message from their state health authority or their children’s hospital for weeks, if ever.

Perhaps the most revealing aspect of the audit is what it says about why the silence occurred. The researchers found that non-responding institutions were not inactive. Some of the organizations that never addressed the acetaminophen controversy published more than 100 posts on unrelated topics during the same study period. That detail, the authors argue, suggests the institutional silence reflected an administrative choice rather than a limitation of capacity or staffing. The infrastructure to communicate existed and was actively being used; it simply was not activated in response to a public health misinformation crisis. Visone framed the finding as a matter of institutional responsibility, noting that major health organizations have a duty to communicate with the populations they serve during times of increased health misinformation, and that at such moments there is nothing more powerful than the truth when it comes to population health.

The quality analysis added a second layer of concern. Among the 26 relevant posts that were published across all institutions, 85 percent used plain-language formatting and myth-busting framing, techniques that communication researchers generally consider best practice for countering misinformation. Myth-busting framing typically involves explicitly naming the false claim, warning readers that it is false, and then substituting the correct information, an approach designed to avoid reinforcing the misconception. Yet even the posts that followed these conventions fell short on accessibility. The average reading level of the relevant posts, measured using the Flesch-Kincaid grade level formula, was grade 11.4, well above the average 8th-grade reading level of adults in the United States. The researchers also assessed readability using the SMOG index, alongside checks for multilingual availability and accessibility features.

That reading-level gap matters because readability formulas estimate the years of education needed to comprehend a text. Content written at an 11th-grade level is effectively inaccessible to a substantial share of the adult population, including many of the pregnant patients and parents of young children most directly targeted by the acetaminophen claims. Compounding the problem, the audit identified no multilingual content across any of the institutions studied, meaning Spanish-speaking families and other non-English speakers had no institutionally produced corrective content in their own languages. For a misinformation event that specifically concerned decisions made during pregnancy, the absence of accessible, translated guidance represents a significant equity gap in the digital public health response.

The study’s methodology reflects a growing effort to bring quantitative rigor to the evaluation of health communication. All analyses were conducted in R version 4.5.3, and the team coded posts for format, content framing, emotional tone, and accessibility features. One of the study’s figures visualizes the timeline of institutional responses as horizontal bars measuring the number of days from September 22, 2025, to each institution’s first relevant Instagram post, with point sizes indicating the total number of relevant posts each institution published. State health departments are absent from that figure entirely, because they had no posts to depict. A second figure breaks down the prevalence of content quality and accessibility features across the 26 relevant posts, grouped by format, framing, tone, and accessibility, providing a template other researchers could apply to future controversies.

The authors argue that the findings point to a gap in administrative infrastructure and policy, not merely in content creation. Their proposed remedy is concrete: pediatric health systems should develop standardized rapid-response protocols that include pre-approved messaging templates written at or below an 8th-grade reading level, multilingual versions of those templates, and clear internal processes for activating effective and accessible communication when emerging controversies arise. The AAP’s Day 1 response demonstrates, the researchers contend, that rapid, high-quality digital communication is achievable even during a fast-moving health controversy. The problem is not that the standard is unreachable; it is that most organizations in the sample never attempted to meet it, leaving families without institutional guidance during an active misinformation event.

The broader significance of the audit extends beyond the acetaminophen controversy itself. As social media grows in popularity as a source of medical information, the pathways by which families encounter health claims have fundamentally changed, and institutional communication strategies have not kept pace. A misinformation event can now reach millions of users within hours, while the audit shows institutional responses arriving on a timescale of weeks or months, if at all. Visone is scheduled to present the abstract during the Oct. 2-6 conference in San Diego, with a poster presentation for the Section on Administration and Practice Management and a featured appearance at a press Soundbite Session. The study offers a practical framework for evaluating and strengthening institutional communication capacity, and its central lesson is likely to resonate with health communicators well beyond pediatrics: in the modern information environment, the speed, readability, and language accessibility of official responses are not secondary concerns but core determinants of whether accurate health information reaches the public at all.

Subject of Research: Institutional responsiveness of pediatric health organizations to acetaminophen-autism misinformation on Instagram

Article Title: Social media analysis finds health institutions delayed or did not respond to false claims inking autism to acetaminophen use during pregnancy

Article References: Social media analysis finds health institutions delayed or did not respond to false claims inking autism to acetaminophen use during pregnancy. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: acetaminophen, autism, health misinformation, social media, Instagram, pediatrics, American Academy of Pediatrics, health communication, children's hospitals, state health departments, readability, public health

The trigger for the exchange is a secondary analysis of the BeNeDuctus trial, conducted by Hoornenborg and colleagues, which examined extremely preterm infants who received paracetamol for pain relief. According to the letter, that analysis found a significantly increased risk of moderate-to-severe bronchopulmonary dysplasia, a chronic lung condition of prematurity, as well as longer requirements for respiratory support among infants exposed to the drug. Because the sample originated from a randomized controlled trial, the finding carries more weight than the observational studies that have fueled suspicion of paracetamol for the past two decades. The letter’s authors commend the trial team while pressing the point that even these researchers continue to call for yet more studies rather than recommending a change in practice.

Bronchopulmonary dysplasia remains one of the most consequential outcomes in neonatology. It arises when the lungs of infants born extremely early fail to develop normally, often after weeks of mechanical ventilation and oxygen therapy, and it predicts years of respiratory illness, rehospitalization and impaired growth. Any drug that measurably raises the risk of moderate-to-severe disease would represent a serious threat to a vulnerable population, which is precisely why the letter frames the question in such stark terms. The authors ask, in effect, how much evidence is enough before the burden of proof shifts from those who suspect harm to those who assume safety.

The biological plausibility of a paracetamol-lung link rests on the drug’s metabolism. Paracetamol is processed primarily in the liver, but a fraction is converted by cytochrome enzymes into a reactive metabolite, N-acetyl-p-benzoquinone imine, which depletes glutathione, the cell’s principal antioxidant defense. The developing lung expresses xenobiotic-metabolizing enzymes, meaning that pulmonary tissue can locally generate toxic metabolites from circulating paracetamol. In a preterm infant, whose antioxidant systems are immature and whose lungs are already under oxidative assault from oxygen therapy and ventilation, additional glutathione depletion could plausibly tip the balance toward arrested alveolar development. Pharmacokinetic studies in very preterm infants have documented measurable exposure not only to the parent compound but to all of its metabolites at standard intravenous doses, underscoring that these tiny patients handle the drug differently from adults.

This mechanistic concern is not merely theoretical. Preclinical work summarized in the pulmonary physiology literature has explicitly called for animal models to understand why the perinatal lung appears uniquely susceptible to acetaminophen, the American name for the same molecule. Meanwhile, a cohort study of extremely preterm infants detected acetaminophen and its xenobiotic metabolites in human milk and reported associations with both bronchopulmonary dysplasia and retinopathy of prematurity, another disease of oxidative stress. There have even been reports of paracetamol overdose in newborns and infants proving life-threatening, a reminder that the therapeutic window in this population is narrower than commonly assumed. Together, these strands sketch a coherent biological story in which a drug once considered benign for the lung may interfere with redox-sensitive developmental processes at exactly the wrong moment.

The broader epidemiological record adds a second, parallel line of concern. Systematic reviews and meta-analyses stretching back more than a decade have consistently reported associations between paracetamol use in pregnancy and wheezing illness or asthma in offspring, and more recent syntheses of prenatal exposure studies have reached similar conclusions. Research in high-risk birth cohorts has also examined early-life acetaminophen exposure in combination with genetic variation in glutathione S-transferase enzymes, finding evidence that the drug’s oxidative burden may interact with inherited detoxification capacity to shape asthma risk into adolescence. Population studies of childhood asthma prevalence continue to list early paracetamol exposure among the modifiable risk factors under scrutiny, and even lactation, long considered a safe channel, has been questioned in the pediatric literature.

What makes the new trial-based analysis so important is the hierarchy of evidence it occupies. Observational studies of drug exposure are notoriously vulnerable to confounding by indication: children who receive more paracetamol tend to be sicker, and sicker infants develop more lung disease regardless of which painkiller they receive. A secondary analysis nested within a randomized controlled trial does not eliminate that problem entirely, since randomization in the parent BeNeDuctus trial was not designed to allocate paracetamol, but it does allow investigators to control for illness severity far more rigorously than most registry or cohort studies can. The fact that a signal for moderate-to-severe bronchopulmonary dysplasia and prolonged respiratory support survived that scrutiny is what lends the letter its urgency.

Yet the letter’s authors are careful not to overclaim causation, and the trial investigators themselves stopped short of a practice change, calling instead for further research into paracetamol’s respiratory effects in preterm infants. That restraint reflects genuine clinical dilemmas. Preterm infants undergo painful procedures, from cannulation to surgery for patent ductus arteriosus, and untreated pain carries its own documented harms, including stress responses that destabilize cerebral blood flow. Paracetamol has become attractive precisely because it avoids the renal, gastrointestinal and platelet side effects of nonsteroidal anti-inflammatory drugs. An overview of systematic reviews on paracetamol’s efficacy and safety concluded that while the drug offers modest analgesic benefit, its safety profile in vulnerable groups deserves continued attention, a conclusion that now reads differently in light of the neonatal data.

The dilemma is sharpened by trends in neonatal care. A recent analysis of fifteen years of respiratory and hemodynamic management in very premature infants documented evolving approaches to bronchopulmonary dysplasia, and observational multicenter registries have compared conservative and medical strategies for managing the ductus arteriosus, a condition for which paracetamol has itself been trialed as a closing agent. In other words, paracetamol is not merely an incidental exposure in the neonatal unit; it is increasingly embedded in treatment protocols. If the drug independently worsens lung outcomes, the implications extend from analgesia guidelines to the very protocols designed to protect the preterm lung, and clinicians would need to weigh analgesic benefit against a respiratory cost that previous risk-benefit calculations never included.

For now, the letter functions as both a summary and a challenge. It gathers the mechanistic, pharmacokinetic, preclinical and epidemiological threads into a single argument that the evidence base has grown substantial enough to demand action beyond another round of observational studies. The authors, who report no competing interests and no external funding, frame their appeal around the families and clinicians they serve, and their central question, how much evidence is enough, is one that guideline committees, regulators and neonatologists will now have to answer explicitly. Whether the answer comes from adequately powered randomized trials of analgesic strategy in extremely preterm infants or from a precautionary shift in prescribing habits, the era in which paracetamol was assumed to be harmless to the developing lung is drawing to a close.

Subject of Research: The association between paracetamol exposure and bronchopulmonary dysplasia in extremely preterm infants

Article Title: Paracetamol and the developing lung: how much evidence is enough?

Article References: Verd, S., Boo, S., & Costa-Orvay, J.-A. (2026). Paracetamol and the developing lung: how much evidence is enough?. Pediatric Research. https://doi.org/10.1038/s41390-026-05532-0

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05532-0

Keywords: paracetamol, acetaminophen, bronchopulmonary dysplasia, preterm infants, neonatology, respiratory support, glutathione, oxidative stress, asthma risk, BeNeDuctus trial, Pediatric Research, drug safety

The compound at the heart of the work is taraxasterol, a pentacyclic triterpenoid extracted from the roots of the common dandelion, Taraxacum officinale. Taraxasterol has long attracted attention for its antioxidant, anti-inflammatory, and anti-apoptotic activities, and it features in several traditional liver-protective herbal formulations. Yet its clinical promise has been strangled by biopharmaceutical realities. The molecule barely dissolves in water, crosses the intestinal wall poorly, and is actively pumped back out of gut cells by P-glycoprotein, a well-known efflux transporter. The research team, led by Zimin Cai and colleagues at Guizhou Medical University, quantified these barriers precisely. In a Caco-2 cell monolayer model mimicking the intestinal epithelium, taraxasterol showed an apparent permeability coefficient of just 0.79 × 10⁻⁶ cm/s. Adding verapamil, a P-glycoprotein inhibitor, boosted its transport roughly 3.6-fold, confirming the efflux problem. In mice, the absolute oral bioavailability of free taraxasterol measured a dismal 6.4 percent.

To attack the solubility problem first, the team turned to nanocrystal technology, which shrinks drug particles to the nanometer scale to dramatically increase surface area and dissolution rate. They prepared taraxasterol nanocrystals using three candidate stabilizers: poloxamer 407, polyvinyl alcohol, and D-α-tocopherol polyethylene glycol succinate, better known as TPGS, an FDA-approved excipient with a hidden talent. TPGS inhibits P-glycoprotein, meaning it can simultaneously stabilize the nanocrystals and silence the efflux pump that would otherwise expel the drug from intestinal cells. At an optimized stabilizer concentration of 1 percent, the TPGS-stabilized nanocrystals measured roughly 148 nanometers in diameter with a narrow size distribution. They also reduced the lattice energy of the crystalline drug, and dissolution testing showed the payoff: while free taraxasterol achieved only 25.6 percent cumulative dissolution over 24 hours, the TPGS nanocrystals reached 88.4 percent, a 3.45-fold improvement. In transport studies, the TPGS formulation raised apparent permeability 2.6-fold and significantly increased uptake by hepatocytes, the liver cells that ultimately need the drug.

But dissolution alone was not enough, and the researchers knew it. Orally delivered nanocrystals face a gauntlet of further obstacles: the acidic, enzyme-rich stomach, the rapidly renewing mucus layer, and the tight junctions that seal the gaps between epithelial cells. Their answer was a mucoadhesive micropatch built from a polyelectrolyte complex of chitosan and carbopol, two oppositely charged polymers that bind electrostatically. The bilayer patch uses ethyl cellulose as a waterproof backing and the chitosan-carbopol complex as the adhesive layer. When hydrated in the intestine, the patch swells into a gel-like network that physically confines the nanocrystals, creating a diffusion barrier that moderates release and prevents aggregation. As the matrix gradually erodes, intact nanocrystals are progressively freed. Infrared spectroscopy and thermal analysis confirmed the electrostatic complex formation, and scanning electron microscopy showed that nanocrystal-loaded patches had smooth, homogeneous surfaces, while patches loaded with free drug displayed ugly crystalline deposits. Over 24 hours, the nanocrystal patches released 80.75 percent of their payload, compared with a mere 23.58 percent for free-drug patches.

The absorption experiments revealed an elegant dual mechanism. In permeation studies across excised porcine intestinal mucosa, the nanocrystal-loaded polyelectrolyte patches achieved the highest cumulative transport of any formulation. In Caco-2 models, including a mucus-containing co-culture that better mimics the real intestinal environment, the patches boosted permeability through two complementary routes. Transcellular uptake rose thanks to nanocrystal internalization and TPGS-mediated efflux suppression. Paracellular transport increased because the chitosan component transiently opened the tight junctions, a process the team verified by measuring transepithelial electrical resistance, which dropped in a time-dependent manner and recovered after patch removal. Immunofluorescence staining showed downregulation of the tight junction proteins ZO-1 and claudin-4, with chitosan identified as the primary contributor to this reversible modulation. Crucially, the opening was temporary, and cell viability remained above 85 percent across all tested concentrations, indicating the barrier disruption does not come at the cost of tissue damage.

To make sure the patches actually reach the intestine rather than sticking in the stomach, the researchers packaged twenty micropatches into a single enteric-coated capsule. In simulated gastric fluid at pH 1.2, the capsules stayed intact for at least two hours; transferred to intestinal conditions at pH 6.8, they disintegrated within fifteen minutes. A magnesium stearate coating prevented the released patches from clumping together. In vivo fluorescence imaging in mice told a striking story: while free dye and plain nanocrystals were swept through the gastrointestinal tract within hours, the micropatch capsules produced strong, persistent signals in the small intestine for up to 12 hours after administration. The patches were seen adhering to the luminal side of the intestinal mucosa, visibly swollen, forming a localized drug depot that maintains a high concentration gradient driving absorption.

The pharmacokinetic consequences were dramatic. Compared with free taraxasterol, the full capsule system produced a 3.1-fold increase in total drug exposure and a 5.8-fold rise in peak plasma concentration, along with a prolonged half-life and reduced clearance. Even more importantly for a liver disease, tissue distribution analysis showed the highest and most sustained drug levels in the liver itself, with hepatic enrichment persisting over 12 hours. This liver-targeting profile means therapeutic concentrations actually reach the site of injury, rather than diffusing uselessly into other organs.

With delivery solved, the team put the platform to the test in two mouse models of liver injury. In the intrinsic model, mice received acetaminophen; in the idiosyncratic model, they received the isoniazid-rifampicin combination. Treatment with the nanocrystal micropatch capsules outperformed both free taraxasterol and plain nanocrystals, and matched or exceeded silymarin, a clinically established hepatoprotective drug used as the positive control. Serum markers of liver damage, including ALT, AST, LDH, alkaline phosphatase, total bile acids, and total bilirubin, all fell significantly, and histological examination showed restored hepatic architecture. Blank capsules without the drug showed no protective effect, confirming the benefit came from taraxasterol itself, not the carrier. The formulation also cut reactive oxygen species and malondialdehyde, restored glutathione and superoxide dismutase, suppressed the inflammatory cytokines IL-1β, IL-6, and TNF-α, and reduced apoptotic cell death, with no detectable toxicity in blood counts or major organs.

To explain these effects mechanistically, the researchers employed network pharmacology, cross-referencing predicted taraxasterol targets against genes linked to both forms of drug-induced liver injury. The analysis identified 80 shared targets concentrated in three pathological axes: oxidative stress, inflammation, and apoptosis. Western blot validation in injured mouse livers confirmed the prediction. The formulation most potently activated the Nrf2/HO-1 antioxidant defense pathway, suppressed stress-activated JNK phosphorylation, and dampened the Bax/Bcl-2 ratio and caspase-3 activation that drive mitochondrial apoptosis. In essence, the delivery platform amplifies the compound’s intrinsic multi-target pharmacology simply by getting enough of it to the liver.

The authors are candid about the work’s limitations: the studies were prophylactic rather than therapeutic, long-term toxicity remains untested, and manufacturing scalability has yet to be proven. Still, the significance of the platform extends well beyond one dandelion molecule. By integrating nanocrystallization, a functional stabilizer that blocks efflux, mucoadhesive polyelectrolyte patches that transiently open tight junctions, and enteric coating for site-specific release, the team has assembled a generalizable blueprint for rescuing poorly soluble, poorly permeable natural products from formulation purgatory. For the many herbal compounds with intriguing pharmacology but hopeless bioavailability, that blueprint could be the difference between laboratory curiosity and real medicine.

Subject of Research: A nanocrystal-mucoadhesive micropatch oral delivery platform enhancing taraxasterol bioavailability for protection against drug-induced liver injury

Article Title: Boosting oral bioavailability of taraxasterol via a nanocrystal-mucoadhesive micropatch platform for potent multi-mechanistic protection against drug-induced liver injury

Article References: Cai, Z., Zhao, H., Wei, M., Cheng, Z., He, H., Xu, J., Xu, S., Huang, J., Xiao, T., Peng, J., Sun, R., Du, Q., & Chen, Y. (2026). Boosting oral bioavailability of taraxasterol via a nanocrystal-mucoadhesive micropatch platform for potent multi-mechanistic protection against drug-induced liver injury. Materials Today Bio, 41, Article 103694. https://doi.org/10.1016/j.mtbio.2026.103694

Image Credits: AI Generated

DOI: 10.1016/j.mtbio.2026.103694

Keywords: taraxasterol, drug-induced liver injury, nanocrystals, oral drug delivery, mucoadhesive micropatch, TPGS, chitosan, carbopol, Nrf2/HO-1 pathway, acetaminophen, bioavailability, hepatoprotection

The clinical stakes are considerable. Bronchopulmonary dysplasia, defined by the need for supplemental oxygen or respiratory support at a corrected gestational age of thirty-six weeks, affects a substantial proportion of infants born before twenty-eight weeks of gestation and is associated with long-term respiratory morbidity, neurodevelopmental impairment, and rehospitalization throughout childhood. Its pathogenesis is multifactorial, involving inflammation, infection, hyperoxia exposure, impaired alveolar and vascular development, and genetic and environmental interactions. Because no single therapy has proven reliably protective, clinicians scrutinize every drug that reaches the developing lung for possible harm, and the analgesics and anti-inflammatory agents used in the first weeks of life are no exception.

The story of these drugs in the neonatal intensive care unit begins with the ductus arteriosus itself. Increased blood flow across a patent ductus arteriosus can be associated with increased pulmonary blood circulation and morbidity, a hemodynamic burden that physicians have tried to relieve since the latter part of the twentieth century by closing a hemodynamically significant ductus in the hope of improving outcomes. The pharmacological workhorses of that effort have been cyclooxygenase inhibitors, chiefly indomethacin and ibuprofen, which reduce prostaglandin signaling and allow the vessel to constrict and close. Both drugs have been used extensively for ductal closure, but both carry side effects and safety concerns in preterm infants, including effects on renal perfusion, gastrointestinal integrity, and platelet function, concerns that have driven a decades-long search for alternatives.

That search produced one of the more memorable accidental discoveries in modern neonatology. As recounted by Sharma and Bhandari, Hammerman and colleagues observed that the use of acetaminophen in preterm infants led to closure of the patent ductus arteriosus, a finding reported in case series that surprised many observers. The mechanism is plausible: acetaminophen acts on prostaglandin synthesis through pathways distinct from classical cyclooxygenase inhibition, and the ductus in the preterm infant remains sensitive to even modest reductions in prostaglandin activity. Following those initial case reports, multiple trials demonstrated that acetaminophen was as effective in closing the ductus as the two established non-steroidal anti-inflammatory drugs, ibuprofen and indomethacin. Crucially, those studies did not look only at closure rates; they also examined associated morbidities, and bronchopulmonary dysplasia emerged as the outcome of greatest interest.

The evidence on that outcome, however, has been reassuringly consistent so far. A large multicenter trial conducted by Gupta and colleagues, published in the New England Journal of Medicine, showed no significant difference in the incidence of bronchopulmonary dysplasia between groups of infants treated with ibuprofen and those given placebo. A retrospective study by Jensen and colleagues compared one group of infants receiving acetaminophen with another receiving ibuprofen or indomethacin and found that the incidence of death or grade 2 to 3 bronchopulmonary dysplasia was similar in both groups. These findings suggested that neither class of drug, when used for ductal closure, clearly worsens the risk of chronic lung disease, at least within the populations and dosing regimens studied.

The BeNeDuctus trial added an important dimension to this debate. This large multicenter randomized non-inferiority trial compared expectant management of a significant patent ductus arteriosus, meaning careful observation without immediate drug treatment, against early treatment with ibuprofen. The trial showed no difference in the incidence of bronchopulmonary dysplasia, necrotizing enterocolitis, or death between the two management strategies. That result was consequential in its own right, because it suggested that routine early pharmacological closure of the ductus may not be necessary for all affected infants. But it also created an unexpected opportunity: some patients in both subgroups received acetaminophen, not for ductal closure but for analgesia, meaning the trial inadvertently enrolled a cohort of extremely preterm infants exposed to the drug for reasons unrelated to their ductus.

Hoornenborg and colleagues exploited that opportunity in their secondary analysis, asking whether paracetamol given as an analgesic was associated with an increased risk of bronchopulmonary dysplasia in extremely preterm infants. The question matters because acetaminophen is among the most widely administered medications in neonatal intensive care, used for procedural and postoperative pain and increasingly considered for ductal closure. If the drug carried even a modest risk to the developing lung, the population-level consequences could be substantial given how many preterm infants receive it. Sharma and Bhandari frame their commentary around exactly this tension between therapeutic utility and pulmonary safety.

Concern about acetaminophen’s effects on the lung is not merely theoretical. Laboratory studies referenced in the commentary have shown that toxic acetaminophen exposure can induce distal lung endoplasmic reticulum stress, proinflammatory signaling, and emphysematous changes in the adult murine lung, and that the developing murine lung appears susceptible to acetaminophen toxicity in ways independent of the hepatic damage for which the drug is best known. Investigators have also raised the possibility that acetaminophen exposure in early life could have lifelong consequences for respiratory health. On the other side of the ledger, ibuprofen has its own pulmonary profile: animal work has documented vascular and pulmonary effects of ibuprofen on neonatal lung development, and recent studies indicate that inhibition of the mitochondrial integrated stress response can ameliorate ibuprofen-induced endothelial dysfunction in models of neonatal hyperoxia-induced lung injury. Both drug classes, in other words, have biological plausibility for lung effects that clinical trials have so far not translated into clear harm.

Interpreting this literature requires attention to the difficulty of the outcome itself. Bronchopulmonary dysplasia is now understood as a syndrome with multiple pulmonary phenotypes in the preterm infant, and its diagnosis has been refined through evidence-based approaches that grade severity by the level of respiratory support required. Newer tools, including magnetic resonance imaging phenotyping and life-course approaches to lung function monitoring after preterm birth, are reshaping how researchers detect subtle drug effects that survival-based or oxygen-based definitions may miss. The commentary’s authors, who have previously argued that bronchopulmonary dysplasia research must move from the bedside to the bench and back again, emphasize that postnatal inflammation, corticosteroid effects on lung development, and gene-environment interactions all complicate any attempt to isolate the contribution of a single analgesic or anti-inflammatory drug.

Where does this leave clinicians and families? The accumulating trial evidence, from the Gupta ibuprofen trial, the Jensen retrospective comparison, the BeNeDuctus trial, and now the Hoornenborg secondary analysis, points toward a consistent conclusion: neither acetaminophen nor the classical non-steroidal anti-inflammatory drugs, as used in contemporary neonatal practice, has been shown to increase the incidence of bronchopulmonary dysplasia or death in extremely preterm infants. At the same time, Sharma and Bhandari’s commentary underscores that the question of pulmonary safety has not been closed as definitively as the ductus itself. Preclinical signals of lung toxicity, the heterogeneity of bronchopulmonary dysplasia phenotypes, and the possibility of long-term respiratory consequences all argue for continued vigilance. As randomized trials of prophylactic acetaminophen for ductal closure and expectant management strategies continue to mature, the developing lung remains the outcome against which every neonatal drug must ultimately be judged.

Subject of Research: Pulmonary safety of acetaminophen and NSAID treatment for patent ductus arteriosus in preterm infants

Article Title: Does use of acetaminophen and/or NSAIDs increase the risk of developing bronchopulmonary dysplasia?

Article References: Sharma, R., & Bhandari, V. (2026). Does use of acetaminophen and/or NSAIDs increase the risk of developing bronchopulmonary dysplasia?. Pediatric Research. https://doi.org/10.1038/s41390-026-05526-y

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05526-y

Keywords: bronchopulmonary dysplasia, acetaminophen, NSAIDs, patent ductus arteriosus, preterm infants, BeNeDuctus trial, neonatology, ibuprofen, indomethacin, Pediatric Research, lung development, neonatal intensive care