Large-scale T1-weighted MRI studies have established grey-matter abnormalities in bipolar disorder (BD), with our group contributing to consensus findings. However, structural connectivity, particularly within emotion- and reward-related circuits, remains poorly understood. Diffusion-weighted MRI (dMRI) enables investigation of white-matter pathways, yet prior work is constrained by small samples, methodological heterogeneity, and unclear medication effects. We conducted the largest dMRI network analysis in BD, relating symptom burden and polypharmacy to tractography-derived connectivity and graph-theoretic metrics.
Natural Compounds in Cranberry Juice May Enhance Antibiotic Treatment of UTIs
Researchers at the Institut National de la Recherche Scientifique in Montreal have found that compounds in cranberry juice may enhance the effectiveness of a commonly used antibiotic for urinary tract infections (UTIs) by altering how bacteria take up the drug. The findings, published in Applied and Environmental Microbiology, show that cranberry juice increased the activity of fosfomycin against uropathogenic Escherichia coli (UPEC) in laboratory testing and reduced the emergence antibiotic resistance mutations in 72% of the E. coli strains studied.
While the findings are encouraging, the researchers noted that the work didn’t show whether consumption of cranberry juice would have the same effects as those shown in the lab. “We don’t know if the metabolites will reach the infection,” said lead author Eric Déziel, PhD, a professor at Institut National de la Recherche Scientifique. “But if they could, then juice may increase the efficacy of antibiotic treatment.”
UTIs are most often caused by UPEC, which accounts for the majority of community-acquired infections and a substantial proportion of catheter-associated infections. Standard treatments include antibiotics such as trimethoprim-sulfamethoxazole, nitrofurantoin, and fosfomycin. While fosfomycin is a recommended first-line therapy because of its broad activity and low resistance rates, past studies have shown that some resistant variants can emerge through mutations that influence bacterial transport systems.
Cranberry products have long been associated with UTI prevention. Earlier theories surmised this was due to fruit’s acidity. Subsequent research, however, has identified specific compounds, including proanthocyanidins and fructose, that interfere with the ability of bacterial to attach to cells lining the urinary tract.
Déziel said that cranberry juice has a long history as folk remedy for preventing and treating urinary tract infections. It was the recent finding of the anti-adhesive properties that prompted further investigation into whether cranberry could influence antibiotic performance.
To test this, the research team exposed 32 clinical isolates of UPEC to cranberry juice in combination with fosfomycin under controlled laboratory conditions. The results showed that in 72% of the strains tested, cranberry juice increased the antibiotic’s inhibitory activity. At the same time, the frequency of spontaneous mutations conferring resistance dropped substantially, in some cases by several orders of magnitude.
The effects of the cranberry juice seems to involve changes in how bacterial cells regulate the uptake of sugars and, by extension, the antibiotic since fosfomycin enters bacterial cells through carbohydrate transport systems, primarily the GlpT and UhpT pathways. Resistance often arises when mutations reduce the activity of these transporters, which then limits the drug entering cells.
Specifically, cranberry juice reduced expression of the GlpT transporter while maintaining or promoting activity through the UhpT system. This shift allowed fosfomycin into the bacterial cell even as other pathways were downregulated. Reporter assays showed that this change sustained antibiotic uptake, while genomic sequencing revealed distinct mutation patterns depending on whether cranberry juice was present.
While the researchers were able to characterize the activity related to the presence of cranberry juice, the compounds responsible for this effect have not been fully identified. Déziel noted that “something in the cranberry juice” induces bacteria to increase uptake through one of these channels, leading to greater absorption of fosfomycin. Previous research has pointed to cranberry-derived molecules that interact with bacterial communication and adherence systems, but their role in modulating antibiotic transport has not been identified.
The study builds on earlier work from Déziel’s lab showing that cranberry extracts can act synergistically with antibiotics. The current research showed that this is also the case with cranberry juice itself. The hope is that simply consuming cranberry juice could produce the same effects as the extracts studied previously.
Despite the promising laboratory data, the researchers said that the findings cannot yet be translated to the clinic. It is still unclear whether the active compounds in cranberry juice are found at the needed concentrations in the urinary tract after consumption, or how much juice would be required to produce a measurable effect.
Future research will seek to identify the specific compounds responsible for the effects shown in this study, determine how they behave in vivo, and assess whether they can be incorporated into treatment strategies.
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Breast Cancer Prevention Drug Endoxifen Shows Promise at Low Doses
A lower-dose alternative to tamoxifen may offer a safer path to breast cancer prevention, according to new research from Karolinska Institutet. The study published in the Journal of the National Cancer Institute, suggests that endoxifen, the most active metabolite of tamoxifen, can reduce mammographic breast density to a similar extent while causing fewer side effects, a balance that has long been difficult to achieve in preventive treatment.
A long-standing trade-off in prevention
Tamoxifen has long been a cornerstone of breast cancer therapy and prevention. It is widely used to reduce recurrence in patients and is also approved for women at increased risk of developing the disease. Yet despite its proven efficacy, its use in prevention has been limited.
Many patients discontinue treatment because of side effects, particularly symptoms resembling menopause such as hot flushes and night sweats. These challenges have highlighted a persistent problem in preventive medicine: therapies can be effective, but if they are not tolerable, adherence—and therefore real-world benefit—remains low.
A more direct and potentially precise approach
Endoxifen offers a different strategy. As the active form of tamoxifen produced in the body, it acts directly on estrogen receptors without requiring metabolic conversion. This makes its effects more predictable and may reduce variability between patients.
It also raises an important question: if endoxifen is the molecule responsible for tamoxifen’s therapeutic effect, could it be used at lower doses to achieve the same benefit with fewer side effects?
Strong biological effects at low doses
To test this idea, researchers administered low daily doses of endoxifen to healthy premenopausal women and monitored changes in mammographic breast density over six months.
Breast density is an established risk factor for cancer and is increasingly used as a marker of response to preventive therapy. Higher density is associated with increased risk, while reductions during treatment suggest a beneficial biological effect.
The results were notable. Even at very low doses, endoxifen significantly reduced breast density. A daily dose of one milligram led to a reduction of around 19 percent, while two milligrams achieved a reduction of approximately 26 percent. These effects are comparable to those typically seen with standard-dose tamoxifen, despite using a fraction of the dose.
Improved tolerability at lower doses
Equally important was how patients tolerated the treatment. While the higher dose of endoxifen was associated with an increase in menopausal symptoms, the lower dose showed a safety profile similar to placebo.
“Our results suggest that a lower dose may be sufficient to affect breast density, whilst also appearing to be better tolerated,” said Mattias Hammarström, head of operations KARMA project at the Karolinska Institute and co-author of the study
This finding is particularly significant because tolerability is one of the main barriers to preventive therapy. A drug that maintains efficacy while minimizing side effects could substantially improve adherence and expand the use of preventive strategies.
Rethinking dosing in preventive therapy
The study highlights a broader shift toward precision dosing, finding the minimum effective dose rather than relying on traditional high-dose approaches.
In this case, the data suggest that maximal biological effect may be achieved at relatively low levels of drug exposure. Increasing the dose further may not provide additional benefit but can increase the likelihood of adverse effects.
This principle has important implications not only for breast cancer prevention but also for other areas of medicine, where balancing efficacy and tolerability is critical.
Implications for clinical practice
If confirmed in larger studies, low-dose endoxifen could become an attractive option for women at increased risk of breast cancer who are currently reluctant to use tamoxifen.
By offering a similar reduction in breast density with fewer side effects, it may lower the threshold for initiating preventive treatment and improve long-term adherence.
However, it is important to note that reductions in breast density do not directly prove a reduction in cancer risk. Longer-term studies will be needed to determine whether these biological changes translate into meaningful clinical outcomes.
Looking ahead
The findings provide a strong proof of concept that targeting the active metabolite directly, and at lower doses, may offer a more refined approach to prevention.
Future research will focus on confirming these results in larger populations and evaluating long-term effects on cancer incidence. There is also growing interest in integrating such approaches into broader prevention strategies, potentially alongside lifestyle interventions and risk-based screening.
For now, the study offers a promising step toward making preventive therapy both effective and tolerable. By reducing side effects without compromising efficacy, low-dose endoxifen could help overcome one of the key barriers in breast cancer prevention, and bring precision medicine principles into preventive care.
The post Breast Cancer Prevention Drug Endoxifen Shows Promise at Low Doses appeared first on Inside Precision Medicine.
STAT+: French regulator fines Novo and Lilly over weight loss ad campaigns
As competition mounts in the red-hot market for weight loss drugs, France’s medicines regulator fined Novo Nordisk approximately $2 million for running “misleading” advertisements for its Wegovy and Saxenda medications.
At the same time, the National Agency for Medicines and Health Products Safety also fined Eli Lilly roughly $127,000 over advertising for its Mounjaro obesity treatment that purportedly amounted to indirect promotion of a medicine for which a prescription is required.
The penalties reflect increasing concern among regulators that weight loss medicines may be misused and, as result, promotions run by pharmaceutical companies are being closely scrutinized. Two years ago, the regulator issued a bulletin on the risks associated with the drugs, especially inappropriate use.
Opinion: Mifepristone court ruling makes drug development riskier for everyone
The biotech industry has long operated on a simple premise: FDA-regulated, evidence-based science determines how medicines reach patients, not litigation. That premise was already tested in an earlier Texas case challenging mifepristone’s Food and Drug Administration approval — an unprecedented effort to unwind decades of scientific review through the courts. It is now, once again, under strain.
On Friday, the 5th Circuit Court of Appeals reinstated an in-person dispensing requirement for mifepristone, a medication that has been used safely by millions for more than two decades. The drug manufacturer, Danco, appealed to the Supreme Court within hours and on Monday morning, SCOTUS granted one-week stay halting the order. In other words, mifepristone is available again through the mail and at pharmacies — but it’s unclear for how long that will be true. And it signals that even well-established, FDA-approved medicines are vulnerable to judicial override of FDA regulatory decisions.
An international and independent scientific foundation for AI governance
Nature Medicine, Published online: 04 May 2026; doi:10.1038/s41591-026-04375-w
An international and independent scientific foundation for AI governance
Phasing out animal research prematurely will maintain gender inequities in medicine
Nature Neuroscience, Published online: 04 May 2026; doi:10.1038/s41593-026-02309-w
Decades of male bias in animal research have left female biology critically understudied. Prematurely phasing out animal research would lock this inequity into future biomedicine, disproportionately harming women.
Stochastic growth and ligand–receptor interaction-mediated stabilization generate stereotyped dendritic arbors
Nature Neuroscience, Published online: 04 May 2026; doi:10.1038/s41593-026-02278-0
Stereotyped dendritic arbors arise from stochastic growth and selective stabilization of dendritic branches. Two pools of guidance receptor are required. Ligand-free receptors drive stochastic growth while ligand-bound receptors stabilize branches.
An Ecological Momentary Assessment Smartphone App for High-Risk HIV Populations: Development and Usability Study
Background: HIV incidence has continued to increase among men who have sex with men (MSM) in Peru, despite intervention efforts. Addressing stigma, risky behaviors, and low medication adherence is key to reducing incidence rates. Ecological momentary assessment (EMA) allows for collection of discrete, real-time data on stigmatized, risky behaviors while reducing recall bias. Objective: The aim of this study was to develop and assess the usability of an EMA smartphone app among MSM with HIV in Peru, which tracks daily health risk behaviors to determine ease of use, usefulness, and satisfaction with the app. Methods: A mixed-method 3-phase study was conducted with 10 MSM with HIV, which included a usability test, 10-day field testing, and a debriefing focus group. Quantitative survey data and user analytics allowed for assessments of acceptability and user compliance. Qualitative interview and focus group data were thematically analyzed for in-depth assessments of user satisfaction. Results: Acceptability of the EMA app was high, with a mean usability rating of 6.4 of 7.0 (SD 0.62), indicating high user satisfaction, ease of use, and usefulness. A 10-day field test demonstrated a high average compliance rate of 93% (93/100), which suggests high feasibility of the app for daily tracking of health risk behaviors among MSM with HIV. Interview and focus group findings indicated that the app was navigable, time-efficient, and holds promise for long-term use, particularly with the inclusion of daily reminders and incentives for prolonged use. Conclusions: EMA apps can provide valuable real-time data while protecting users’ privacy. This formative work lays the foundation for future larger-scale EMAs of substance use and sexual risk behaviors among high-risk HIV populations, and for the development of just-in-time interventions to address stigma, improve medication adherence, and reduce risky behaviors.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/d5969f95bbfd7056b7362eebeea780e8" />
Data-Driven Tool Identifies Individuals at Highest Risk of Obesity-Related Disease
A new clinical risk model may transform how obesity is managed, by identifying which individuals are most likely to develop serious complications, regardless of their body mass index (BMI).
Developed by researchers at Queen Mary University of London and the Berlin Institute of Health, the tool, called OBSCORE, uses just 20 routinely collected clinical variables to predict the future risk of 18 obesity-related conditions, ranging from type 2 diabetes to cardiovascular disease.
Published in Nature Medicine, the study challenges the long-standing reliance on BMI as the primary metric for assessing obesity-related health risk.
Moving beyond BMI
BMI has long served as a simple proxy for obesity, but it fails to capture the biological heterogeneity of patients. Two individuals with similar BMI can have vastly different risks of developing complications.
The new model addresses this limitation directly. As described in the study, it “provides information beyond BMI” by integrating multiple dimensions of health into a unified risk score.
These include demographic data, clinical biomarkers, disease history, and lifestyle factors, variables already commonly available in healthcare settings.
The findings show that BMI alone is a poor discriminator of risk. The model consistently outperformed BMI-based approaches across all tested outcomes.
Large-scale data enables precision risk prediction
To build the model, researchers analyzed health data from nearly 200,000 individuals with overweight or obesity from the UK Biobank.
Using an interpretable machine learning framework, they screened more than 2,000 potential predictors and distilled them into a core set of 20 features that best predicted long-term health outcomes.
The resulting OBSCORE model estimates the 10-year risk of developing 18 conditions, including cardiovascular disease, kidney disease, sleep apnea, and metabolic disorders.
The model demonstrated strong predictive performance, with median concordance indices around 0.75 across outcomes, indicating robust discrimination between high- and low-risk individuals.
Hidden high-risk individuals
One of the most striking findings is that high-risk individuals are not always those with the highest BMI.
A substantial proportion of individuals classified as high risk fell into the “overweight” category (BMI 27–30 kg/m²), rather than obesity. In some outcomes, up to ~40% of those in the highest risk group had BMI below the obesity threshold.
This reveals a critical gap in current clinical practice: individuals who may benefit from intervention could be overlooked simply because they do not meet BMI-based criteria.
On the other hand, some individuals with obesity may have relatively low risk and may not require intensive intervention.
Strong risk stratification across diseases
Beyond prediction, the scientists believe that OBSCORE enables meaningful risk stratification. Individuals in the highest risk group showed dramatically higher rates of disease compared to those in the lowest group.
For example, the study reports:
- Up to 89-fold higher risk for chronic kidney disease
- 42-fold higher risk for type 2 diabetes
- 47-fold higher risk for cardiovascular mortality
These differences exceed those observed when comparing individuals based solely on BMI categories, underscoring the added value of multidimensional risk assessment.
Clinical and healthcare implications
The implications of these findings are significant, particularly in the context of emerging obesity therapies.
Highly effective drugs such as GLP-1 receptor agonists and dual incretin therapies have transformed treatment options, but their high cost and limited availability make patient prioritization essential.
As the authors note, current systems lack robust frameworks to identify which patients should receive treatment.
OBSCORE offers a potential solution by enabling risk-based allocation of interventions, ensuring that treatment is directed toward those most likely to benefit.
This could improve clinical outcomes while optimizing healthcare resource use.
Toward implementation in clinical practice
One of the key strengths of OBSCORE is its practicality. Unlike many predictive models, it relies on a small number of variables that are already routinely collected, making it suitable for integration into electronic health records.
The researchers envision the model being used as a decision-support tool in clinical settings, complementing rather than replacing existing frameworks.
External validation in independent cohorts—including populations of different ancestry, demonstrated strong generalizability, further supporting its potential for real-world deployment.
Limitations and next steps
Despite its promise, the model requires further validation in broader populations, including younger individuals and more diverse healthcare settings.
Additionally, while OBSCORE effectively stratifies risk, translating these predictions into actionable treatment thresholds will require clinical consensus and cost-effectiveness analyses.
The authors also emphasize that the model identifies predictive, not necessarily causal, factors, and should be interpreted accordingly.
Taken together, the findings mark a shift toward precision medicine in obesity, moving from simplistic metrics like BMI to data-driven, individualized risk assessment.
By capturing the complex interplay of metabolic, clinical, and behavioral factors, OBSCORE could enable earlier intervention, better targeting of therapies, and improved long-term outcomes for patients living with overweight and obesity.
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