Acute peripheral facial palsy (APFP) sometimes known as Bell’s palsy is a common neurological condition and is marked by the acute onset of lower motor weakness on one side of the face. Whereas spontaneous recovery is widespread, there is a significant rate of incomplete recovery, synkinesis, or enduring functional and psychosocial disability of patients. The past decades witnessed the improvement of the diagnostic and therapeutic plans, particularly the pharmacological and adjunctive ones, due to the developments in pathophysiological and clinical trials and the creation of guidelines. This narrative review summarizes the existing evidence on the classification, diagnosis, and treatment of APFP, particularly corticosteroid disease treatment, antiviral medication, combination therapy, adjunct, and rehabilitative therapies, and the future of precision medicine. Randomised controlled trials and high-quality systematic reviews have shown evidence in support of the early initiation of systemic corticosteroids within 72 h of symptom onset as the foundation of treatment practice, improving the likelihood of achieving full facial nerve recovery and less morbidity in the long run. Conversely, antiviral monotherapy has not demonstrated significant clinical benefit with combination therapy with antivirals potentially presenting some benefit to older patients and with severe cases of paralysis. New data highlight the significance of risk stratification, electrophysiological testing, and focal rehabilitation to maximize the results and reduce the sequelae. The developments in artificial intelligence, the work on biomarkers and adaptive clinical trial designs will likely enable more personalized prognostication and treatment choice. In general, a shift towards precision risk-based approaches to the management of acute peripheral facial palsy is also being considered and emerging diagnostic strategies, promotion of the use of corticosteroids as early as possible and focused adjunctive operations that are tailored to a child are becoming the key to improving functional outcomes in the long term.
Shifting the goalposts in obesity drug development
Nature Medicine, Published online: 23 June 2026; doi:10.1038/s41591-026-04462-y
Obesity drug development must move beyond an emphasis on ever-greater weight loss to prioritize tolerability, sustainable benefits and medication persistence; two recent trials exemplify this shift, with more underway.
A Study to Learn About the Study Medicine Called Ponsegromab in Adults With Lung Cancer-Associated Significant Weight Loss
Conditions: Non-small Cell Lung Cancer (NSCLC); Cachexia
Interventions: Drug: ponsegromab; Drug: placebo
Sponsors: Pfizer
Not yet recruiting
Interventions: Drug: ponsegromab; Drug: placebo
Sponsors: Pfizer
Not yet recruiting
Psychotherapy initiation is associated with discontinuation of psychotropic medications without dose escalation: a ten-year real-world cohort study (2014-2024)
BackgroundIncreasing psychotropic prescribing has raised concerns about long-term safety and regimen complexity in mental health care. Although psychotherapy is an established treatment, its role in medication optimization and psychotropic medication reduction in real-world practice across patient subgroups remains insufficiently characterized.ObjectiveTo evaluate whether initiation of psychotherapy is associated with short-term changes in psychotropic medication exposure and regimen complexity, and to examine differences by sex, age, and diagnostic category. Methods: A retrospective cohort study was conducted using anonymized pharmacy dispensing data from the Mental Health Service of Hospital Marina Baixa (Alicante, Spain) between 2014 and 2024. Patients with at least one active prescription for a benzodiazepine or antidepressant within 90 days before psychotherapy initiation were included. Psychotropic exposure was compared in symmetric 90-day pre- and post-therapy windows using number of active agents, total Defined Daily Doses, and prevalence of benzodiazepine and antidepressant use, with stratified analyses by sex, age group, and diagnosis.ResultsThe cohort comprised 86,502 patients and 20.76 million dispensations. The median number of psychotropic medications decreased from 5 to 2 (p < 0.001), while total dose remained stable (median Defined Daily Dose ≈ 21.7; p = 0.999). Benzodiazepine use declined from 87.6% to 67.5% and antidepressant use from 81.8% to 68.8% (both p < 0.001). Men were more likely than women to discontinue benzodiazepines (odds ratio 1.27, 95% confidence interval 1.13–1.43), and simplification increased with age (median reduction −1 in <18 years to −4 in ≥65 years). The largest benzodiazepine reductions occurred in depressive, personality, and episodic mood disorders (−23 to −27 percentage points).ConclusionsIn routine public mental health care, psychotherapy initiation is associated with substantial simplification of psychotropic treatment regimens without increasing overall medication dose, supporting a potential role in facilitating rational medication simplification.
Gene Therapy Restores Brain Function and Behavior in Fragile X Syndrome
A University of California, Riverside-led research team has developed a gene therapy that restored production of a missing brain protein, corrected abnormalities in brain circuitry, and improved behavior in a mouse model of Fragile X syndrome (FXS). The study, published in the journal Molecular Therapy Nucleic Acids, tested an adeno-associated virus (AAV)-based therapy carrying a normal human version of the FMR1 gene to produce the Fragile X messenger ribonucleoprotein (FMRP) and found that early treatment normalized several measures of brain activity while improving social behavior, exploratory behavior, and cognitive flexibility.
“In a typical brain, FMRP acts like a brake or a volume control,” said senior author Iryna Ethell, PhD, a professor of biomedical sciences at the UC Riverside School of Medicine. “Without it, neural circuits become overactive and less efficient, which contributes to many of the developmental and behavioral challenges associated with FXS.”
FXS is the most common single-gene cause of autism spectrum disorder. According to the researchers, the disorder typically manifests from expansion of CGG repeats in the 5′ untranslated region of FMR1. The mutation causes methylation and silencing of the gene, leading to a major reduction or complete loss of FMRP, an RNA-binding protein that regulates numerous messenger RNAs involved in synapse formation, maturation, and function. Loss of the protein can lead to abnormal synaptic activity and increased cortical hyperexcitability.
FXS can produce sensory hypersensitivity, seizures, anxiety, intellectual disability, developmental delays, repetitive behaviors, and social communication difficulty. Current treatments for this syndrome don’t seek to cure it, rather they are aimed at managing the associated symptoms of anxiety, hyperactivity, irritability, aggression, depression, and seizures.
The therapy developed by the research team was designed to replace missing FMRP rather than repair the original mutation. To do this, the researchers used an AAV9 viral vector to deliver human FMR1 isoform 7, one of the most abundant forms of the protein found in the brain. The therapy was tested in newborn mice lacking FMRP via intracerebroventricular injections at either a low or high doses.
The work built on earlier research that explored the potential of AAV-mediated restoration of FMRP in rodent models. These prior studies used a range of viral serotypes, promoters, delivery routes, and FMRP isoforms and showed they could partially or completely correct specific biochemical, physiological, and behavioral abnormalities. The researchers noted that studies involving mouse and rat FMRP homologs had shown that restoring the protein could improve a range of Fragile X-related deficits.
The current study showed that high-dose treatment produced the strongest positive effects in the mouse models. Electroencephalography showed normalization of baseline gamma power, improvements in responses to sound, reduced background neural activity, and improved habituation to repeated auditory stimuli. The therapy also restored abnormal patterns of brain-wave coupling that have been associated with Fragile X-related dysfunction.
Behavioral testing showed that these improvements persisted into adulthood. Mice receiving the higher dose displayed normalized exploratory behavior, improved social preference, and better performance in probabilistic reversal learning, a measure of cognitive flexibility that requires adapting when previously rewarded behaviors stop producing rewards.
“Fragile X mice tend to persist with an old solution even after the rules change,” Ethell said. “After treatment, they became much better at adapting, performing similarly to mice with normal FMR1 function.”
The researchers noted that their work showed the importance of delivering at therapy for FXS early in its development. They said that widespread distribution of the potential new gene therapy throughout the brain was necessary to achieve a therapeutic benefit. There was a clear relationship between the proportion of neurons expressing the therapeutic gene and the degree of functional recovery, which indicated that restoring FMRP in a sufficient number of cortical cells is critical for correcting any behavioral deficits.
While a promising step, the investigators said that the work was a preclinical study and that future research will now focus on developing delivery methods that can of have broad distribution across the human brain. The team also believes their approach could have broader applications.
“Beyond FXS, the findings may provide a roadmap for treating other genetic neurodevelopmental disorders caused by the loss of a single critical protein,” Ethell said. “Our study shows it may be possible to restore function across complex brain networks by replacing a missing gene. That gives us reason to be optimistic about the future of genetic medicine.”
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Sleep Habits Can Influence Effects of Alzheimer’s Disease Risk Genes
Research led by Edith Cowan University in Australia suggests the impact of genetic mutations that impact Alzheimer’s disease risk are influenced by a person’s sleep habits.
As reported in the journal Alzheimer’s & Dementia, the researchers confirmed links with aquaporin-4 gene (AQP4) variants and changes in brain volume, atrophy and cognition linked to Alzheimer’s disease.
The investigators also showed how long people sleep, how long it takes them to fall asleep, how often their sleep is disturbed, and how good or poor their sleep is overall contributed to the effect of these mutations.
“Our study shows that individuals carrying certain AQP4 variants showed faster grey matter loss when they reported shorter sleep,” said study co-author Ayeisha Milligan Armstrong, PhD, a researcher at Edith Cowan University, in a press statement.
“It’s not just which genes you carry—it’s how those genes interact with the world around you. The same variant can look protective or detrimental depending on how someone is sleeping. That’s important, because sleep is one of the few modifiable factors people can actually act on.”
Researchers now think the brain gets rid of amyloid‑beta using a kind of plumbing system that washes waste away along the outside of blood vessels. In this system, fluid moves through the spaces around blood vessels, helped by tiny water channels called aquaporin‑4, encoded by AQP4, which sit on the parts of astrocyte cells that wrap tightly around those vessels.
“Given that AQP4 has been identified as an important mediator of brain amyloid beta clearance, variation within the AQP4 gene has been investigated in relation to neurodegenerative diseases and their associated phenotypes,” write the authors.
“A bi-directional relationship has been observed between suboptimal sleep and increasing brain amyloid beta accumulation…Importantly, a previous study utilizing data from the Australian Imaging, Biomarker and Lifestyle cohort reported that the relationship between sleep and cross-sectional brain amyloid beta burden was moderated by genetic variants in AQP4.”
To investigate this link further, the researchers studied 351 cognitively normal people already showing ongoing build‑up of brain amyloid‑beta on positron emission tomography (PET) imaging. They genotyped the group for 13 mutations in the AQP4 gene and also assessed sleep duration and quality, brain volume, amyloid burden and cognition scores.
Several AQP4 variants interacted with sleep measures to predict gray‑matter atrophy, brain ventricular volume, white‑matter volume, and cognitive decline. For example, people carrying certain variants who also had shorter sleep duration were more likely to have faster grey‑matter loss, and other variants magnified the impact of poorer global sleep quality on ventricular enlargement in the brain.
One variant showed a direct association with better global cognitive performance and two other variants seemed to be linked to less cognitive decline as sleep disturbances increased.
“We’ve known for a while that poor sleep and Alzheimer’s risk are linked,” said first author Tenielle Porter, PhD, also a researcher at Edith Cowan University.
“What this shows is that rather than assuming everyone at risk follows the same pathway, a more targeted and personalized approach to Alzheimer’s prevention may be needed. But we’re not at the point of recommending genetic testing; our findings need replication in larger and more diverse cohorts.”
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Magnetic Algae Microrobots Boost Chemotherapy Penetration in Bladder Tumors
Researchers from the University of Edinburgh and Xiamen University have developed microscopic algae-based robots capable of delivering chemotherapy directly into bladder tumors, significantly improving drug penetration and therapeutic efficacy in preclinical models.
The study, published in Nature Nanotechnology, describes a machine-guided drug delivery platform that combines biodegradable microalgae, magnetic control, real-time ultrasound imaging, and artificial intelligence-assisted navigation. In mouse models of bladder cancer, the system achieved more than a tenfold increase in drug penetration and reduced tumor burden to less than 3% of that observed with conventional chemotherapy delivery.
“Our microrobots are engineered from tablet-like microalgae, can be remotely guided to the tumor using real-time imaging feedback, and release drugs exactly where they are needed to drive rapid tissue penetration in a minimally invasive way,” said study co-lead Qi Zhou, PhD, of the University of Edinburgh.
Addressing a major challenge in bladder cancer therapy
Bladder cancer is one of the most common malignancies worldwide, with approximately 75% of cases diagnosed as non-muscle-invasive disease. Standard treatment typically involves surgical removal of visible tumors followed by intravesical chemotherapy, in which drugs are delivered directly into the bladder through a catheter.
While this approach limits systemic toxicity, its effectiveness is often constrained by poor penetration of drugs through the bladder’s protective barriers and into tumor tissue. Much of the chemotherapy remains near the surface, requiring prolonged exposure times and higher drug doses to achieve therapeutic benefit.
To overcome these limitations, the research team developed what they call a “drug-loaded magnetic Coscinodiscus granii” (DMCG) microrobot. The platform uses naturally occurring diatom algae, whose porous silica shells provide an ideal structure for carrying therapeutic cargo. The algae are coated with magnetic nanoparticles, loaded with the chemotherapy drug doxorubicin, and sealed with a protective polymer layer that enables controlled drug release.
Magnetic navigation and intelligent control
Unlike conventional drug carriers that rely on passive diffusion, the algae microrobots can actively move through the bladder under the influence of externally applied magnetic fields.
Researchers developed multiple modes of movement, including rolling, tumbling, spinning, and swirling. Rolling modes allow the robots to travel efficiently through the bladder while minimizing premature drug leakage. Once they reach a tumor, the robots switch to rotational modes that generate localized fluid flows around the porous algae structure, accelerating drug release and enhancing penetration into surrounding tissue.
The system incorporates real-time ultrasound imaging and deep learning-based tracking algorithms that identify both the tumor and the microrobot swarm. Using this feedback, robotic magnetic controllers can autonomously guide the swarm to target regions and trigger localized drug delivery.
The researchers liken the collective behavior of the microrobots to schools of fish or flocks of birds moving in coordinated swarms through complex environments.
Enhanced drug penetration
A key innovation of the platform is its ability to generate convective fluid flow around the tumor.
The rotating microrobots create microscopic currents that transport drug molecules more efficiently than diffusion alone. Laboratory experiments demonstrated that this mechanism substantially increased release of doxorubicin from the algae carriers and improved penetration through both hydrogel barriers and three-dimensional tumor spheroids.
In tumor spheroid models, the rotating microrobots increased drug penetration depth by approximately 150 micrometers and boosted overall fluorescence intensity, a measure of drug accumulation, by nearly 370% compared with non-actuated controls.
The approach also allowed researchers to separate transport and release functions. Swarms could travel rapidly in locomotion mode before switching to localized swirling behavior that increased drug release by more than threefold compared with transport mode alone.
Strong anti-tumor effects in mice
The team then evaluated the technology in an orthotopic mouse model of bladder cancer.
Using ultrasound guidance, the researchers navigated the microrobot swarms directly to bladder tumors, where they generated localized flow fields and released chemotherapy. Histological analysis revealed that tumor-specific accumulation of doxorubicin increased dramatically compared with free drug administration. Mean fluorescence intensity within tumors increased by more than 1,000%, while the tumor-to-normal tissue ratio rose from 0.56 to 3.6.
The researchers subsequently conducted a one-week treatment study consisting of four intravesical chemotherapy sessions delivered on alternating days.
The results were striking. Bioluminescence imaging showed that tumor burden in mice receiving microrobot-assisted therapy fell to just 2.36% of that observed in animals treated with free doxorubicin and 0.59% of that seen in untreated controls. The authors estimate this corresponds to more than a 40-fold improvement in therapeutic efficacy.
According to the researchers, the treatment did not produce detectable systemic toxicity. Body weight remained stable throughout the study, and analyses of major organs and blood chemistry revealed no significant adverse effects. Tumors treated with the microrobots also exhibited increased apoptosis and reduced cellular proliferation compared with controls.
Toward minimally invasive cancer therapy
The investigators believe the platform could eventually support more effective and less invasive treatment strategies for bladder cancer.
Current intravesical chemotherapy often requires patients to retain therapeutic agents in the bladder for extended periods. In contrast, the algae microrobot system achieved its therapeutic effects after approximately 30 minutes of active treatment while maintaining bladder tissue integrity and avoiding mechanical damage to the urothelium.
The authors suggest the technology may be particularly valuable for patients who are poor candidates for surgery or as an adjunctive therapy following tumor resection to reduce recurrence risk.
Future work will focus on refining the automated imaging-feedback system, studying long-term outcomes and pharmacokinetics, and evaluating the platform in larger animal models before potential clinical translation. Researchers also envision adapting the technology for drug delivery in other body cavities, including abdominal and gynecological applications.
“This study highlights a non-invasive approach to overcoming the biological barriers that limit drug penetration in bladder tumors,” said Professor Xiaohui Yan, PhD, of Xiamen University. “We are now discussing translational follow-up studies with hospitals, with the long-term aim of clinical trials after further preclinical validation and regulatory review.”
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Paradoxical reflex bradycardia in paroxysmal sympathetic hyperactivity following traumatic brain injury: a case report
BackgroundParoxysmal sympathetic hyperactivity (PSH) is a devastating complication of traumatic brain injury (TBI), characterized by the simultaneous onset of various manifestations due to sympathetic overactivity. Paradoxical bradycardia, an uncommon manifestation of PSH, is poorly characterized, and there is limited evidence regarding its clinical features, pathophysiological mechanisms and targeted management.Case presentationA 25-years-old male sustained severe traumatic brain injury in a nighttime motorcycle collision with a parked vehicle and underwent multiple neurosurgical procedures. He developed typical PSH on day 48 post injury, with a Paroxysmal Sympathetic Hyperactivity Assessment Measure (PSH-AM) score of 27. On the 92nd day post-injury, the patient developed persistent resting bradycardia (40–66 beats/min) after cranioplasty, while a reduced maximum heart rate (140–159 beats/min) was noted during PSH episodes. He subsequently experienced an acute PSH episode with severe bradycardia (38–43 beats/min, PSH-AM score of 20). After excluding common predisposing factors, intravenous isoproterenol (initial dose 4 μg/min, titrated to 2 μg/min) was administered in combination with anti-PSH medication regimen, and the patient’s clinical symptoms were relieved. The patient was discharged in a stable condition and had no further episodes of bradycardia at the 3-months follow-up.ConclusionParadoxical bradycardia represents an atypical clinical phenotype of post-TBI PSH, likely mediated by an atypical Cushing reflex secondary to fluctuating intracranial pressure elevations during PSH exacerbations. Clinically, for TBI patients with unexplained bradycardia, potential primary causes should be actively explored, with particular attention to monitoring dynamic changes in intracranial pressure.
Physical factor therapies for insomnia: a narrative review of mechanisms, clinical evidence, and phenotype-guided applications
Although pharmacological treatments for insomnia remain widely prescribed, their long-term use is constrained by risks of tolerance, dependence, and residual daytime effects. This has prompted growing interest in non-pharmacological interventions that target insomnia’s underlying mechanisms. This narrative review examines five physical factor therapies for insomnia: auditory stimulation, phototherapy, thermotherapy, electrical stimulation, and magnetic stimulation. They are classified according to their primary sites of action into peripheral sensory modulation, central neuromodulation, or systemic autonomic regulation. In each context, research findings about circadian entrainment, thermoregulatory promotion of falling asleep, attenuation of cortical hyperarousal, and restoration of autonomic balance are discussed. Clinical evidence from randomized controlled trials and meta-analyses is critically appraised, with emphasis on therapeutic efficacy, safety, and limitations. Overall, physical factor therapies may constitute promising adjunctive options for selected insomnia phenotypes, but current evidence remains heterogeneous and preliminary for several modalities. Recent advances in portable and home-based technologies support their feasibility, although long-term effectiveness, adherence, and cost-effectiveness remain to be established. Future research should prioritize larger sham-controlled trials, objective sleep and circadian outcomes, standardized protocols, biomarker-guided stratification, and closed-loop intervention systems.
Post-marketing safety of lecanemab: a real-world study based on FAERS database, multicenter cohort and network pharmacology
IntroductionLecanemab is a monoclonal antibody targeting amyloid-beta (Aβ) approved for treating Alzheimer’s disease (AD) with mild cognitive impairment or mild dementia. Continuous monitoring of its real-world safety profile remains essential. This study aimed to analyze lecanemab-related adverse events (AEs) using the FDA Adverse Event Reporting System (FAERS) database and a multicenter cohort, and explored mechanisms via network pharmacology.MethodsWe conducted an updated disproportionality analysis of FAERS data from 2023 to 2024 to identify disproportionate reporting signals (SDRs). A multicenter retrospective cohort study was performed, including lecanemab users from June 2024 to February 2025. Data were collected from electronic medical records of five tertiary hospitals. AEs were identified and influencing factors of AE occurrence were analyzed. Additionally, a drug-gene interaction network was constructed to explore potential mechanisms.ResultsIn the FAERS analysis of 2,764 AEs from 1,389 lecanemab users, 12 of 41 positive SDRs were prioritized, with 75% (9/12) being nervous system disorders, primarily amyloid-related imaging abnormalities (ARIA). In the cohort study, 29.05% (43/148) of patients experienced AEs, with infusion-related reactions being most common. Age was identified as a risk factor for AE occurrence [OR (95% CI): 1.109 (1.011–1.215), P = 0.028], while pre-treatment significantly reduced AE incidence. Gene enrichment analysis suggested potential links between lecanemab-related genes and AEs.DiscussionThis study provides real-world evidence on the risk profile of lecanemab, highlighting the importance of continued safety monitoring. These findings may inform discussions about the risks associated with anti-amyloid treatments and warrant further confirmation in large-scale prospective studies.