Background: In older adults with chronic constipation, symptoms of defecation difficulty often persist despite improvements in bowel movement frequency. However, constipation-related symptoms have rarely been examined as independent outcomes. Objective: The objective of this study is to explore factors associated with constipation-related symptoms, less than 3 spontaneous bowel movements per week, straining during bowel movements, a sensation of incomplete evacuation, and a sensation of anorectal obstruction or blockage. Methods: A cross-sectional web-based survey was conducted to collect patient-reported data. Constipation-related symptoms were defined according to the Rome IV criteria. Each symptom was treated as a binary variable in the analyses. Multivariable logistic regression analyses were used to examine associations between stool characteristics and medication, treatment processes, and lifestyle-related factors. Stool characteristics were classified using the Bristol Stool Form Scale, with hard stools defined as types 1 and 2. Results: We enrolled 546 participants and investigated the following constipation symptoms: less than 3 spontaneous bowel movements per week (n=226, 41.4%), straining (n=330, 60.4%), sensation of incomplete evacuation (n=344, 63.0%), and sensation of anorectal obstruction or blockage (n=242, 44.3%). Multivariable logistic regression analyses for these outcome variables showed that hard stool was consistently and independently associated with all constipation-related symptoms (odds ratio [OR] 1.86‐4.66). Symptom-specific associations that remained significant after false discovery rate adjustment included lower physical activity with less than 3 spontaneous bowel movements per week (OR 0.86, 95% CI 0.77‐0.96), stimulant laxative use with the sensation of incomplete evacuation (OR 2.01, 95% CI 1.22‐3.31), and lower adherence to the prescribed dosage with the sensation of anorectal obstruction or blockage (OR 0.87, 95% CI 0.78‐0.97). In contrast, the experience of adverse effects was associated with a higher probability of less than 3 spontaneous bowel movements per week and the sensation of anorectal obstruction or blockage. Conclusions: In older adults with chronic constipation, different constipation-related symptoms showed distinct patterns of association, while hard stool consistency emerged as a common factor across symptoms. These exploratory findings may support symptom-oriented assessment and help inform individualized management approaches using electronically collected patient-reported outcomes.
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Macrophage Membrane-Derived Nanoparticles Shows Potential Against Candida Infections
By using tiny particles made from the membranes of human immune cells, scientists from the University of California, San Diego and the University of Missouri have created antifungal nanoparticles that target Candida albicans, a fungus responsible for oral and vaginal yeast infections as well as bloodstream infections. Tests in mice with severe Candida infections show that the macrophage-derived nanoparticles reduced the amount of fungus in major organs, including heart, kidneys, lungs, and spleen. The mice also had improved survival rates.
Full details are published in Cell Biomaterials in a paper titled “Cell membrane-derived nanotherapeutic for combating Candida albicans infections.” In it, the scientists write that “this bioinspired nanodisc not only disrupts fungal membranes directly but also enhances host immune clearance, achieving potent antifungal activity.”
Current treatment options for fungal infections are limited and there are growing concerns about drug resistance. Existing medications typically target specific parts of a fungal cell and can lose effectiveness as fungi evolve resistance. The nanoparticles described in the current paper have a more potent strategy. Besides damaging fungal membranes, they also boost the body’s natural immune defenses to better fight infections.
According to the scientists, each nanodisc measures about 10-20 nanometers, about 1,000 times smaller than a normal macrophage. Their tiny size is an advantage as it allows them to fuse directly with fungal cell membranes and destabilize them, which is harder for full-sized macrophages.
To create the nanodiscs, the scientists isolated the outer membranes of the macrophages and broke up them up into tiny pieces. They then fused them onto disc-shaped nanoparticles made from a biodegradable polymer. Since the nanodiscs are built from macrophage cell membranes, they retain the same receptor proteins that the immune cells use to recognize and attack Candida. This means that the nanodiscs can identify and attach to fungal cells more effectively than those made from other cell types such as red blood cells.
Once attached, the nanodiscs weaken the fungal cell’s protective outer membrane until tiny openings form. As the membrane breaks down, the cell’s contents leak out while external substances seep in ultimately killing the fungus. Because this treatment strategy physically damages the fungal cell rather than targeting a specific molecule, the developers believe that it may be harder for the fungus to evolve resistance.
The nanodiscs also provide other countermeasures. They reverse the suppression of antifungal chemicals produced by macrophages during infection, and prevent Candida from forming biofilms that help to shield fungal cells from drugs and the immune system. Testing also revealed that the treatment was effective when administered both before and after infection suggesting that it could also be used as a preventative.
For their next steps, the scientists will further evaluate the antifungal potency of the nanodiscs against a broader range of pathogenic fungal species.
The post Macrophage Membrane-Derived Nanoparticles Shows Potential Against <i>Candida</i> Infections appeared first on GEN – Genetic Engineering and Biotechnology News.
Prevalence of pharmacologically treated attention deficit hyperactivity disorder in children, adolescents, and adults: systematic review and meta-analysis
IntroductionAttention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental paediatric disorders and persists into adulthood, although it is frequently underdiagnosed and underrecognized in adult populations. In this context, the prevalence of pharmacologically treated individuals diagnosed with ADHD represents an important quality indicator for ADHD management.AimTo estimate the pooled prevalence of pharmacologically treated individuals with ADHD in different age groups in Europe and worldwide.MethodsA comprehensive search of PubMed/MEDLINE was conducted to identify relevant articles published up to October 4, 2024. The present systematic review and meta-analysis examined ADHD prevalence using clinically confirmed diagnoses and treatment data from official records. The exclusion criteria included studies that lacked clinical confirmation of ADHD and/or relied exclusively on parental reports for diagnostic or medication information. The prevalence of pharmacologically treated individuals with ADHD was calculated as a percentage, with a 95% confidence interval (CI). A meta-analysis was performed in R using a random-effects model. Heterogeneity was calculated using I². Prediction intervals were additionally computed to reflect the expected range of prevalence in future studies. Risk of bias was assessed for all included studies using a standardized, previously published methodology. The study was prospectively registered in PROSPERO (CRD42020200220) and adhered to the PRISMA guidelines for systematic review and meta-analysis (2020).ResultsThe systematic review identified 13 studies (12 studies included in the meta-analysis) with substantial variation in age-specific reporting. The pooled prevalence of pharmacologically treated ADHD was 73.4% (95% CI: 63.4–81.5), with extremely high between-study heterogeneity and wide 95% prediction interval (29.6%–94.5%), reflecting substantial variation across settings. The pooled prevalence estimate should be interpreted with caution due to substantial between-study heterogeneity and is not intended for direct clinical inference. Geographic analyses revealed no significant variation across countries. Sex-stratified analyses showed no significant difference between males and females, although point estimates were slightly higher in males.ConclusionThe prevalence of pharmacological treatment among individuals with ADHD appears to vary across age groups and settings Overall, findings indicate substantial variation in pharmacological treatment of ADHD by age, with consistently high heterogeneity limiting the precision of pooled estimates.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020200220.
Health system learning enables generalist neuroimaging models
Nature Medicine, Published online: 10 July 2026; doi:10.1038/s41591-026-04497-1
NeuroVFM, trained on routine health system MRI and CT scans, learns general neuroimaging representations that improve diagnosis, report generation and triage, showing how private clinical data will power safer, more accurate medical AI.
Anti-LAG-3 with or without anti-PD-1 in recurrent glioblastoma: a phase 1 trial
Nature Medicine, Published online: 10 July 2026; doi:10.1038/s41591-026-04475-7
In a non-randomized phase 1 trial, patients with recurrent glioblastoma received anti-LAG-3 relatlimab with or without anti-PD-1 nivolumab, showing that both monotherapy and combination therapy are safe and result in encouraging preliminary clinical response signals.
FDA quietly pushes back deadline on electric shock ban
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STAT+: How a Boston doctor built a following as a ‘loud and unafraid’ voice in the Trump era
Jeremy Faust cuts through a hallway of Boston’s Brigham and Women’s Hospital on his way to see a patient who is struggling to breathe. It’s the start of his evening shift, and the emergency department hums with ambient sound: bleeping monitors, the rumbling wheels of medical carts, the squeaky soles of hustling staff. People on gurneys line the corridor, some wincing in pain, others chatting with relatives.
On this Wednesday evening in May, Faust is working what is typically a quieter shift, as far as emergency departments go. Still, he is overseeing a team of doctors, students, and physician assistants, and will tend to more than two dozen patients before signing off for the night.
It’s an understatement to say Faust likes to keep busy. Minutes earlier, he’d posted an article on his influential Substack newsletter, Inside Medicine, providing an update on a major international news story. An alert sent to the newsletter’s nearly 85,000 subscribers announced his “scoop”: Twenty-six passengers aboard the MV Hondius, the hantavirus-hit cruise ship docked at the time off Cape Verde, had disembarked much earlier than previously known — raising the possibility they could spread the rare virus in the United States.
Adverse childhood experiences and academic burnout among Chinese traditional medicine students: the serial mediating role of rumination, self-control, and resilience
IntroductionMedical students are vulnerable to academic burnout, particularly those with a history of adverse childhood experiences (ACEs). Although early adversity has been linked to burnout, the precise psychological processes underlying this association remain insufficiently understood. This study examined whether rumination, self-control, and resilience were statistically associated with the relationship between ACEs and academic burnout among medical students.MethodsA cross-sectional questionnaire survey was conducted among 1,889 medical students from Heilongjiang University of Chinese Medicine. Measures included ACEs, academic burnout, rumination, self-control, and resilience. Pearson correlation analysis, and serial mediation analyses were performed. Sensitivity analyses were conducted using alternative ACE codings, and supplementary analyses were used to compare alternative mediator orderings.ResultsACEs were positively associated with academic burnout (β = 0.187, p < 0.001). Rumination, self-control, and resilience were each statistically linked to the ACEs-burnout association through significant indirect pathways. After inclusion of the mediators, the direct association between ACEs and academic burnout was no longer significant. The overall pattern was broadly consistent across continuous, binary, and ordinal ACE operationalizations. Supplementary analyses further indicated that several alternative mediator orderings were also statistically plausible.ConclusionThese findings suggest that rumination, self-control, and resilience are statistically associated with the relationship between ACEs and academic burnout. However, because the study was cross-sectional, causal ordering cannot be established. Longitudinal studies are needed to clarify the temporal sequence of these psychological processes and to determine whether targeting them may help reduce academic burnout.
Stem Cell Therapy Shows Promise in First Human Parkinson’s Disease Trial
A landmark Phase I/II clinical study led by researchers at Skåne University Hospital and Lund University has shown that transplanting stem-cell-derived dopamine progenitor cells into the brain is feasible. Eight patients with Parkinson’s disease (PD) received transplants of STEM-PD, a cryopreserved, off-the-shelf dopaminergic progenitor product derived from human pluripotent stem cells. The three-year Phase I/II, open-label, multicenter, single-arm, dose-escalation study identified no serious side effects linked to the transplanted cells during the first year of follow‑up.
“The possibility of replacing dopamine neurons that are lost in Parkinson’s disease has been a long-standing goal in the field,” said Malin Parmar, professor of cellular neuroscience at Lund University, and lead of the STEM-PD program. “The findings represent an important milestone for regenerative medicine approaches in Parkinson’s disease and support continued clinical development of stem cell-based therapies.”
Results from the study were reported by Parmar and colleagues in Nature Medicine. In their paper, titled “Human embryonic stem cell-derived dopaminergic cells for Parkinson’s disease: a Phase I/II open-label trial,” the team wrote, “In conclusion, particularly in the context of other recently published trials using human PS cell-derived dopaminergic cell therapies for PD, these findings further support the continued development of this therapeutic approach, including evaluation of the STEM-PD product in larger patient cohorts.”
Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, the authors wrote. In Parkinson’s disease, patients lose nerve cells in the brain that produce dopamine, which leads to symptoms such as slowness of movement, stiffness, gait disturbance, and tremor. “The hallmark pathology of PD involves progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the subsequent loss of their projections to the striatum,” the team explained. Current treatments are medications that replace the lost dopamine, but over time these medications often become less effective and cause side effects.
“Intracerebral transplantation of stem cell-derived dopaminergic progenitors to replace lost endogenous dopaminergic neurons offers a new potentially restorative therapeutic approach for PD,” the investigators continued. Scientists have been working to develop standardized and scalable dopamine cell therapy products derived from pluripotent stem (PS) cells, including human embryonic stem (ES) cells and induced PS (iPS) cells, they noted. “Several such products are now in clinical development … with early safety and feasibility data emerging.”
The transplanted stem cell-based dopamine nerve cell product tested in the newly reported trial is designed to replace the cells that produce dopamine, and the goal is that after being transplanted, the transplanted cells will mature into new dopamine-producing nerve cells in the brain. The STEM-PD trial aimed to evaluate the safety, tolerability, and feasibility of intraputaminal transplantation of STEM-PD in patients with moderately advanced PD.
Eight individuals with Parkinson’s disease received the transplanted cell product at two different doses, followed by 12 months of immunosuppression to prevent graft rejection. All patients were treated at Skåne University Hospital. Seven participants completed 12-month follow-up, and one participant died from a pulmonary infection that was not directly related to the cell product.
The surgical procedure was generally well tolerated, and no graft-induced involuntary movements were observed in the transplanted participants. Clinically, patients remained stable. Imaging using dopamine PET scans provided early indications of graft survival at both 6 and 12 months post-transplantation. Six of the seven participants substantially reduced their dopaminergic medication, a result that will be evaluated over time. In their paper, the team wrote in summary, “This Phase I/II clinical trial involving the bilateral intraputaminal transplantation of the STEM-PD dopaminergic progenitor cell product demonstrates its feasibility with no unexpected safety concerns from the cell product.”
Roger Barker, MD, professor of clinical neuroscience at the University of Cambridge, clinical lead of STEM-PD and clinical PI at the U.K. site, said: “This represents an exciting new departure on repairing the brain of individuals with Parkinson’s using dopamine cells- an approach pioneered in Lund some 40 years ago using fetal dopamine cells. The STEM-PD trial harnessing the expertise of scientists and clinicians from Lund and Cambridge has enabled us to undertake and deliver on one of the first ever stem cell-derived dopamine cell therapies for patients with Parkinson’s, and we hope this will be the beginning of an exciting new programme that may ultimately benefit the wider Parkinson’s community.”
Gesine Paul-Visse, MD, professor in neuropsychiatric research and lead PI at Skåne University Hospital, said, “Reaching this primary endpoint and being able to show that the cell product is safe is a great achievement for this trial, our team, the participating patients, but also for all patients suffering from Parkinson’s disease. We are hopeful that the early signs of cell survival and clinical improvement we observe will continue to increase over time and are excited to continue the development of this cell therapy.”
The STEM-PD research team will now continue the long-term follow-up of the participants to further evaluate safety, graft function, and clinical benefit. “Secondary and exploratory outcomes will evaluate the course and efficacy of clinical features, the survival of grafted dopaminergic cells at 36 months as well as additional safety signals occurring between 12 and 36 months and any dose–response effects,” the investigators stated. “Further evaluation of the grafts up to 36 months will determine whether the implanted cells continue to grow, mature and reinnervate the putamen after 12 months.”
STEM-PD builds on decades of research in dopamine cell replacement therapy for PD at Lund University and pioneering work in translation of pluripotent stem cell technology from experimental studies into clinical evaluation. The STEM-PD trial is the first pluripotent stem cell trial approved in Sweden and the first for PD in Europe. “The initiation and execution of this clinical trial have only been possible through close collaboration between scientists, clinicians, GMP manufacturing teams, regulatory experts and, most importantly, the participating patients,” concluded Parmar. In their report, the authors stated, “The STEM-PD trial adds further important confirmatory and complementary evidence to the recently reported feasibility and short-term safety of PS cell-derived dopaminergic progenitor transplantation in PD.”
The academic Phase I/IIa trial was conducted in collaboration with Novo Nordisk. Cellular Intelligence, a Boston-based company, recently acquired the STEM-PD program and will lead its next phase of clinical development, including a planned Phase II trial. The STEM-PD cells and their continued development hold IND clearance with FDA Fast Track Designation, and Cellular Intelligence aims to advance the program through Phase III to market approval.
STEM-PD is an academic European clinical translation initiative, focused on developing stem cell-based therapies for Parkinson’s disease. The program is led from Lund University with partners from Skåne University Hospital, Cambridge University Hospital, and University College London and combines expertise in stem cell biology, GMP manufacturing, neurosurgery, clinical neurology, and regenerative medicine to advance pluripotent stem cell-derived dopamine neuron therapies toward clinical application.
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Crohn’s Disease Phage Therapy Neutralizes Inflammatory E. coli in Mouse Model
By taking advantage of the microbe-targeting capabilities of bacteriophages (phages), researchers at McMaster university have devised a supportive therapy for Crohn’s disease that disarms a type of E. coli bacteria that drives inflammation in the gut without disrupting the broader gut microbiome. The team showed that the phage therapy also improved responses to low doses of a conventional corticosteroid in a mouse model of Crohn’s disease, suggesting treatment could both improve outcomes and lower the risk of side effects from standard therapies.
Senior and co-corresponding author Elena F. Verdu, PhD, professor in the Department of Medicine and director of the Farncombe Family Digestive Health Research Institute, and colleagues reported on their study in Science Translational Medicine, in a paper titled “Phage intervention improves colitis and response to corticosteroids by attenuating virulence of Crohn’s disease–associated bacteria,” in which they noted “By reducing bacterial virulence mechanisms without substantially disrupting microbial balance, phage-based treatments align with personalized microbial therapeutics in IBD.”
Inflammatory bowel diseases (IBDs) such as Crohn’s disease and ulcerative colitis (UC) are chronic inflammatory conditions of the gastrointestinal (GI) tract that have strong microbial components, with patients often displaying disruptions in the delicate microbiome of the gut. “Recent studies have demonstrated that changes in the composition and function of the gut microbiota precede CD onset by up to five years,” the author wrote. However, they continued, “Current medications focus on suppressing symptoms and inflammation and can fail, in part, because they do not address underlying microbial drivers.”
Patients with Crohn’s disease tend to harbor strains of adherent-invasive E. coli (AIEC) that adhere to and invade epithelial cells in the intestines. “AIEC is distinct from other IBD-associated taxa because of its ability to adhere, invade, and survive in intestinal epithelial cells,” the team continued. Clinicians will sometimes prescribe antibiotics during symptom flares to try to target these bacteria, but antibiotics aren’t a long-term solution. They are non-specific and can perturb the microbiome even further, and with frequent use lead to side effects.
AIEC bacteria can be difficult to identify and selectively target, making them an important test case for more precise microbiome-based therapies. “One challenge is that AIEC are defined by what they do, not simply by how they appear in a microbiome analysis,” said Verdu. “To identify them, we need to test their behavior, such as their ability to adhere to and invade intestinal cells and persist in immune cells.”
Verdu, together with first author Kyle Jackson, PhD, at Farncombe Family Digestive Health Research Institute, and colleagues theorized they could navigate these roadblocks and neutralize virulent E. coli using bacteriophages. “Phages work like a lock-and-key system—each phage targets only certain bacteria. That precision gives us a way to intervene without wiping out the entire microbiome,” explained co-author Zeinab Hosseinidoust, PhD, associate professor in the Department of Chemical Engineering and the School of Biomedical Engineering.
The concept of using phages to target inflammatory bacteria is already being trialed, the authors noted in their paper. “Commercial phage ‘cocktails’ are presently being evaluated in clinical trials (NCT04737876 and NCT03808103) against proinflammatory bacterial taxa associated with IBD. These trials seek to target adherent-invasive Escherichia coli (AIEC), a group of bacteria enriched in patients with active CD compared with those in remission or healthy individuals.”
For their newly reported study the team developed a Crohn’s disease mouse model with a defined microbiome, and then screened a collection of phages, looking for those that could infect one strain of E.coli, NRG857c, isolated from patients with Crohn’s disease.
The results showed that their approach significantly reduced gut inflammation. The phages did not eliminate the bacteria entirely. Instead, they altered their behaviour by supressing a molecular “grappling hook” that helps AIEC attach to the gut lining and trigger immune responses. When that virulence mechanism was turned off, inflammation subsided.
One phage, designated HER259, countered the bacteria’s virulence by infecting it and switching off a genetic region named fimS. This region promotes the expression of FimH, which supports the bacteria’s ability to adhere to cells and trigger inflammation.
“HER259 ameliorated colitis in gnotobiotic models and attenuated the virulence of AIEC strain NRG857c, including suppression of the FimH adhesin through inversion of the fimS promoter to its ‘off’ orientation,” the authors wrote. “Withdrawal of HER259 treatment led to reversion of the fimS promoter and reactivated colitis.”
Hosseinidoust noted, “The bacteria were still there but they lost the traits that drive inflammation. We like to think of it as knocking out a few teeth. The bacteria can’t do as much damage anymore.” Withdrawing HER259 treatment led to reversion of the fimS promotor, and reactivated colitis, the authors noted.
The researchers also found that phage therapy enhanced the effectiveness of a commonly used steroid treatment for IBD, budesonide. When combined with the phage, a lower-than-standard dose of the drug produced benefits comparable to higher doses of the drug alone.
The HER259 phage in addition enhanced the therapeutic effect of subtherapeutic budesonide independent of microbial drug metabolism, the team wrote. While phages have previously been shown to increase the effectiveness of antibiotics, this is the first time a positive collaboration between phage and a non-antibiotic drug has been reported.
“In summary, using phage HER259 and NRG857c as a model phage–proinflammatory bacterium pair, we reveal a previously unknown mechanism by which targeted phage therapy disrupted key virulence markers in the CD-associated E. coli strain, reducing acute and chronic colitis, preventing reactivation, and enhancing therapeutic responses to budesonide.”
The findings point to a precision‑medicine approach for IBD. The bacterial function targeted by the phage can be measured in stool samples and was found to be higher in a subset of patients with Crohn’s disease, suggesting a potential way to identify those who could benefit most from this therapy.
“If we can identify which patients carry the harmful bacterial function, we could, in the future, intervene with a targeted therapy designed specifically to turn down that activity,” says Verdu. “This is what personalized medicine should look like: matching the right biological tool to the right patient,” added Hosseinidoust.
Next steps for the team include evaluating broader collections of bacterial strains from IBD patients and developing combinations of phages—work that brings the approach closer to human trials.
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