Neurological and psychiatric disorders are a highly prevalent source of global disability. For the majority of these conditions, including autism spectrum disorder (ASD), disease-modifying treatments remain unavailable, and existing pharmacological interventions are largely palliative.
STAT+: ‘Are we just going to give up and die like every other generation?’
BERKELEY, Calif. — On a sunny Thursday morning, around 100 people sat on folding chairs beneath a lawn tent preparing to do a mass blood draw. Standing onstage with a tangle of morning glories as his backdrop, Robby Wade, CEO of at-home testing company Rythm Health, warned that the process might be a little chaotic given the size of the crowd.
Wade explained how to activate the heating pads by popping a small silver coin, prompting a chorus of admiring oohs from the audience as rays of warming crystallized gel spread like the sun. Within a few minutes, everyone, me included, had matching stick-on Tasso devices trickling blood from our upper arms into test tubes that promised to give insights into the health of our hormones, metabolisms, various organs, and biological age.
“It’s like Theranos, but it works,” said the gentleman sitting in front of me, who had recently given a talk on bodyoids — creating headless sacs of organs to replace aging people’s failing hearts and kidneys.
It was the first day of Vitalist Bay, a longevity conference-slash-festival launched last year that brings together founders, investors, biohackers, researchers, and the generally death-averse to discuss how to forestall, or even beat, our demise. Held at an event space (and rationalist AI doomer hub) called Lighthaven, the grounds were dotted with well-padded wicker patio furniture and taffy-pink rose bushes. Along with hearing talks on topics like cryopreservation and delaying menopause, attendees might opt to attend a workshop on longevity therapeutics led by a co-founder of BioAge Labs, drop by a Krav Maga lesson, or take a sound bath. The mood was buoyant, the Oura rings ubiquitous, the stakes existential.
“Are we just going to give up and die like every other generation?” Adam Gries, co-founder of the conference and larger Vitalist movement, asked in his opening remarks.
Giving up and dying had been basically my plan, though hopefully not for a long time. Perhaps that was because I hadn’t given enough thought, as the people at Vitalist Bay had, to considering the alternatives. As the field works to make the showdown against death and aging mainstream, the longevity community is now in the midst of shifting from “a movement to really more of an industry,” said Christine Peterson, co-founder of the Foresight Institute, which focuses on research on longevity and nanotechnology.
Multicenter Prospective Study on MRI AI Model for Midline Glioma Subtyping and Prognosis:
Conditions: Gliomas Harboring IDH1 and/or IDH2 Mutations; Glioma Glioblastoma Multiforme; Glioma of Brainstem; Glioma, Diffuse Midline, H3K27M-mutant; Glioma : Oligodendroglioma or Astrocytoma; Gliomas
Sponsors: Xiangya Hospital of Central South University
Recruiting
Sponsors: Xiangya Hospital of Central South University
Recruiting
Gene Therapy Shows Promise Against TDP‑43 Neurodegeneration in Mice
Among the proteins implicated in age‑related neurodegeneration, TDP‑43 has taken on growing importance: its misfolding and mislocalization are now linked to frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and are estimated to be present in more than half of Alzheimer’s cases. Faster cognitive decline, greater brain atrophy, and worsening memory loss are all associated with TDP-43.
Now, researchers at the University of California, San Diego (UCSD), are testing a gene‑therapy strategy designed not to remove TDP‑43, but to help neurons withstand its toxicity. In a study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, the team reports that systemic delivery of a gene called SynCav1 to brain cells protected cognition and preserved neuronal structure in a mouse model of TDP‑43 proteinopathy. The study is titled, “Systemic delivery of synapsin-promoted caveolin-1 overexpression ameliorates pathological TDP-43–induced cognitive decline and neurodegenerative changes.”
The approach centers on caveolin‑1, a scaffolding protein that organizes membrane signaling domains and supports neuronal resilience. The researchers packaged SynCav1 into a modified AAV vector capable of crossing the blood–brain barrier—a notable departure from many CNS gene therapies that require direct injections into brain tissue. Once delivered, SynCav1 boosted caveolin‑1 expression across the brain and spinal cord.
“Many therapies for neurodegenerative disease focus on removing toxic proteins, but neurons are also losing their ability to cope with that stress,” said senior author Brian Head, PhD, professor of anesthesiology at UCSD School of Medicine and research career scientist at the Veterans Affairs San Diego Healthcare System. “Our findings suggest that strengthening the neuron’s resilience itself may be a powerful therapeutic strategy, even when toxic proteins are already present.”
In treated TDP-43A315T mouse models, SynCav1 preserved learning and memory deficits, behavioral domains typically impaired by TDP‑43 pathology. The therapy also reduced levels of pathological TDP‑43 in the cortex and hippocampus. At the subcellular level, SynCav1 protected mitochondrial structure, stabilized membrane lipid rafts (MLR), and maintained MLR-associated GluN2A receptor expression, which is essential for excitatory synaptic signaling.
The mechanistic insight emerged from a striking observation: in diseased mice, TDP‑43 mislocalized to membrane lipid rafts, disrupting signaling hubs and degrading synaptic ultrastructure. “We found that TDP‑43 is not only accumulating in the wrong subcellular compartments…but also disrupts cellular processes that are essential for neurons to communicate with one another,” said co‑corresponding author Shanshan Wang, MD, PhD, assistant professor of anesthesiology at UCSD School of Medicine. “SynCav1 appears to help preserve this molecular machinery and subcellular localization.”
Electron microscopy revealed that SynCav1 also mitigated mitochondrial hyper‑fragmentation and excessive fission signaling. Axonal myelin integrity was preserved as well, as reported in the study.
“What is especially exciting is that we saw protection across multiple levels—behavior, synapses, axons, membrane signaling, and mitochondrial structure,” Head added. “That kind of broad neuroprotection is exactly what is needed in complex disorders like TDP‑43‑related dementias.”
The authors emphasize that the work is preclinical, but the results support SynCav1 as a neuron‑centric therapeutic candidate that could be applicable across multiple TDP‑43‑linked diseases.
Brian P. Head, PhD, holds equity in and serves as a non‑paid scientific advisory board member for Eikonoklastes Therapeutics. Other authors reported no competing interests.
The post Gene Therapy Shows Promise Against TDP‑43 Neurodegeneration in Mice appeared first on GEN – Genetic Engineering and Biotechnology News.
Differences in Safety Risks Across Languages in Health-Relevant Queries: Vulnerability Analysis of Large Language Model Responses
Background: Large language models (LLMs) such as ChatGPT are increasingly used to support health-related queries and decision-making. However, these models can be “jailbroken” through adversarial prompts that bypass safety filters and elicit harmful or medically inappropriate responses. In health care contexts, such vulnerabilities pose serious risks. Understanding how jailbreak susceptibility varies across languages is essential for developing robust safeguards and promoting equitable access to safe health information. This paper may contain examples that may be deemed harmful in terms of violence, self-harm, and drug abuse. Objective: This study aims to systematically compare and contrast the vulnerability of a health LLM for jailbreaking across 3 languages: English, Spanish, and Hindi (transliterated using the Latin alphabet), based on emoji and permutation cipher attacks. Methods: We analyzed 1000 input prompts per language, drawn from the BeaverTails dataset, across 3 harm categories: self-harm, violence, and drug abuse. Each prompt was modified using emoji and permutation cipher techniques, resulting in 6000 input-output pairs. Model responses were evaluated by human coders to determine the success rate of jailbreak attempts across languages and cipher types. Results: Hindi prompts showed the highest vulnerability, with 787 successful jailbreaks using emoji ciphers and 873 using permutation ciphers. Spanish and English followed, with lower success rates across both cipher types. Differences in jailbreak success across languages and cipher strategies were statistically significant. Additionally, attacks targeting violence-related prompts were more successful overall than those targeting drug-related or self-harm content, indicating variation in vulnerability by harm type. Conclusions: The findings of this formative study reveal that LLM safety performance varies substantially across languages and harm categories, raising concerns about equitable protection in multilingual health communication. Disparities in access to harmful content may contribute to downstream health risks. Strengthening multilingual content moderation and developing language-aware safety mechanisms are critical steps toward creating safer and more inclusive health AI systems.
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The Role of eHealth Literacy and Patient Adherence in Mediating Health Consciousness and Perceived Severity in Quality of Life Among Young Patients With Ischemic Heart Disease: Cross-Sectional Study
Background: Ischemic heart disease (IHD) is becoming increasingly prevalent, with a rising trend significantly impacting the quality of life (QoL) of young Malaysians. Objective: This study aimed to investigate the direct and indirect relationships between eHealth literacy (eHealth) and patient adherence (PA), as well as their mediating effects on the associations of health consciousness (HC) and perceived severity to chronic disease (PS) with QoL among young patients with IHD. Methods: A cross-sectional study was conducted at 2 hospitals, recruiting eligible patients through consecutive sampling at outpatient cardiology clinics. Data were collected via a validated self-administered questionnaire encompassing sociodemographic and socioeconomic status, medical history, and PS, HC, eHealth, PA, and QoL data. Structural equation modeling analysis was used to evaluate the relationships. The ethics approval was obtained from the Ethical Committee of Universiti Kebangsaan Malaysia Medical Centre (FF-2021-117). Results: A total of 136 young patients with IHD participated in the study. Structural equation modeling analysis revealed that eHealth had the strongest positive effect on QoL (β=0.287, =.002), followed by PA (β=0.245, =.02), and HC (β=0.218, =.02). Two significant mediation models were identified, aligning with the Transactional Model of eHealth Literacy theory. The first model demonstrated parallel mediation, where eHealth (β=0.125, =.008) and PA (β=0.083, =.046) significantly mediated the relationship between HC and QoL. The second model indicated serial mediation through eHealth and PA between HC and QoL (β=0.042, =.049). The parallel mediation model exhibited medium predictive power and was deemed the best-fit model. Conclusions: The parallel model pathway showed significant direct and indirect associations between eHealth, PA, HC, and QoL, with eHealth demonstrating the strongest association. Higher eHealth and PA were associated with QoL among young patients with IHD; interventions to support eHealth warrant further investigation in longitudinal or interventional studies.
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Virtual Reality–Based Training in Radiologic Technology for Contrast-Enhanced Computed Tomography Brain Imaging: Randomized Controlled Trial
Background: Radiologic technology (RT) education faces challenges in bridging theory and practice due to limited clinical opportunities. While virtual reality (VR) enables safe and repeatable practice, a systematic instructional design framework is needed to develop scalable, procedure-focused modules. Objective: This study evaluates the Radiologic Technology Virtual Reality (RTVR) framework that integrates 360-degree video capture, instructional overlays, interactive assets, and an immersive content authoring platform to deliver a contrast-enhanced computed tomography (CECT) brain scan module. Methods: In this open-label, parallel-group, randomized controlled trial, 36 year-2 and year-3 RT students with no prior clinical training in diagnostic radiology at a university hospital in Thailand were randomly allocated (1:1) to a VR group or a conventional document-based instruction (control) group. The VR group completed the VR module, a grounded instructional design framework using 360-degree videos and a structured prebrief and debrief, for 20 minutes using a head-mounted display. The control group studied standard curriculum materials for the same duration. Blinding of participants was not possible. Outcome assessment was blinded. The primary outcome was declarative knowledge gain, assessed using a 20-item multiple-choice test before and after intervention. Secondary outcomes included technology acceptance, student satisfaction, and physiological responses during VR immersion. Results: All 36 randomized participants (VR: n=18, control: n=18) completed the study and were included in the analysis. Experts validated the module as suitable and highly appropriate. Students reported high technology acceptance and satisfaction. Both VR and conventional methods produced substantial gains in declarative knowledge. No statistically significant difference in knowledge gain was detected between groups (test × group: unstandardized regression coefficient β=.056, 95% CI −1.360 to 1.473, =.94). Year-2 students, who had less prior clinical exposure, showed larger pretest to posttest knowledge gains compared to year-3 students. Physiological monitoring showed a reduction in heart rate across the session, while blood pressure remained stable. No adverse events or VR-related discomfort requiring discontinuation was observed. Conclusions: The RTVR framework, which uses a real 360-degree video of authentic clinical settings, offers a scalable approach to procedural VR content creation without requiring specialist technical skills, distinguishing it from prior VR studies in radiography. These findings support the RTVR framework as a feasible, evidence-informed supplement to RT curricula for knowledge-focused procedural teaching, with learning outcomes comparable to those of conventional instruction in this context. Trial Registration: Thai Clinical Trials Registry TCTR20260309005; https://www.thaiclinicaltrials.org/show/TCTR20260309005 (retrospectively registered)
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Helping Older Veterans Use Mental Health Apps: Qualitative Interviews and Development of a New Program
Background: Mobile mental health apps may provide an accessible, scalable, and private avenue for older veterans who may not otherwise seek or receive care to address their mental health concerns. However, older veterans may experience barriers to using these apps that need to be addressed to facilitate effective use. Such support could be effectively implemented within the US Veterans Health Administration to facilitate the use of the United States Department of Veterans Affairs’ established mental health apps and to benefit older veterans with mental health concerns. Objective: This study aimed to (1) assess older veterans’ interest in and barriers to using mental health apps to address problems such as difficulties with social connection, and (2) develop and pilot a coaching program to address barriers that older veterans experience in using mobile devices and apps. Methods: Rapid qualitative analysis of semistructured qualitative interviews with 12 older veterans identified themes regarding interest, barriers, and preferences for support for using mobile apps. These themes informed the development of a coaching program, which was piloted with 13 older veterans to assess acceptability, feasibility, and resultant signals of changes in mobile device proficiency. Results: Most veterans expressed interest in using mental health apps. One of the most common barriers was familiarity and proficiency with mobile devices and app technology. Other common barriers included usability or accessibility of the technology or app, motivation, and memory. Veterans reported interest in receiving coaching support. Though the majority of veterans expressed some preference for more individualized and in-person support, they identified both benefits and drawbacks to all potential coaching modalities (group vs one-on-one, in-person vs remote)—including issues of individualizable and guided assistance, feasibility and accessibility of the support, and group settings as potential avenues for social connection as well as potential susceptibility to challenging social dynamics and interactions. Mobile Device and App Learning (MoDAL)—a 2-session, interactive, remote educational group—was developed and piloted. Most veterans who participated found MoDAL helpful. Participants’ mobile device proficiency showed a statistically significant improvement on average pre- to post-MoDAL, although this effect was small, and the small sample size limits the strength of the conclusions. Conclusions: Older veterans do have some interest in using mobile mental health apps to address mental health–related issues. However, they experience critical barriers, including a lack of familiarity and proficiency with the technology. MoDAL may improve older veterans’ comfort and proficiency with mobile devices and apps, which could address one of the barriers that impacts downstream engagement in mental health apps and other virtual care modalities.
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Heart Attack Byproduct Linked to Brain Inflammation and Cognitive Decline
Researchers at the University of Ottawa has found that a heart attack may trigger neurological disorders and cognitive decline, and have identified the reactive molecule methylglyoxal as a potential driver of neuroinflammation after myocardial infarction. The research, published in the journal Advanced Science, adds to a growing body of evidence that injury to the heart can directly alter brain function through the “heart-brain axis.”
“Methylglyoxal has been widely studied for its role in metabolic diseases, including diabetes, but much less is known about its function in other diseases. In a previous study, we discovered that methylglyoxal was produced by dying heart tissue after a heart attack. Based on this evidence, we predicted that methylglyoxal in the blood would target other organs and tissues, including the brain—and this is what we did indeed observe,” said senior author Erik Suuronen, PhD, a professor in the department of surgery and director of the BEaTs research program at the University of Ottawa Heart Institute.
The researchers found that methylglyoxal-derived advanced glycation end products (MG-AGEs) accumulated in the brains of mice within hours after myocardial infarction and remained elevated seven days later. This accumulation resulted in neuroinflammation, activation of microglia and macrophages, increased inflammatory signaling, and disruption of the blood-brain barrier.
The study examined five brain regions in female and male mice after they induced myocardial infarction. Brain tissue was collected at six hours and seven days after the cardiac event. Researchers measured levels of MG-H1, the major MG-derived advanced glycation end product, along with glyoxalase-1, inflammatory cytokines, receptors for AGEs, activated microglia, and macrophages.
The work builds on a multiple earlier research studies linking cardiovascular disease and neurological disorders. Prior clinical studies have found that myocardial infarction and heart failure are associated with increased risks of dementia, depression, anxiety, and cognitive impairment. Patients with depression after myocardial infarction also face a greater risk of future cardiovascular events.
The heart-brain axis is the bidirectional relationship between cardiac and neurological function similar to the gut-brain axis. Changes in heart function can influence the brain, while neurological disease can also affect cardiovascular health. While the biological factors relating to this interaction are still emerging, the new research indicates that methylglyoxal may be one factor contributing to this relationship.
MG is produced as a byproduct of glycolysis and can react with proteins, lipids, and DNA, contributing to cellular dysfunction. Conditions associated with myocardial infarction, such as ischemia, inflammation, oxidative stress, and metabolic shifts toward anaerobic glycolysis, promote MG production while limiting its detoxification.
The mouse studies showed that the brainstem had the highest accumulation of MG-H1 after myocardial infarction, followed by the cortex. These same regions also showed elevated expression of inflammatory markers and receptors associated with MG-mediated signaling. Male mice exhibited higher MG-AGE accumulation and greater neuroinflammation than females in several brain regions.
The team also documented increases in inflammatory markers including NF-κB, TNF-α, and activated microglia across multiple brain regions. The cortex and brainstem demonstrated the highest inflammatory responses. According to the authors, the findings suggest a “region-specific vulnerability to glycation-induced stress post-MI.”
The findings could have implications for better understanding how heart attacks contribute to long-term neurological disease risk, including dementia and Alzheimer’s disease. The researchers noted that MG-AGEs already have recognized roles in neurodegenerative disease and mental health disorders.
The researchers have already used the information from the study to develop a peptide designed to trap methylglyoxal and prevent cellular damage, as a potential new therapy. The peptide will be tested for its ability to protect the brain after myocardial infarction.
“Given the increased risk of subsequent heart attacks or death in heart attack patients who experience depression or anxiety, being able to alleviate these conditions could reduce subsequent major cardiac events and improve the lives of countless patients, filling an urgent unmet clinical need,” Suuronen says.
The researchers said future work will examine how MG-driven inflammation contributes to neuron death and behavioral changes after myocardial infarction. They also plan further research to better understand the glyoxalase detoxification system, including glyoxalase-1 activity and glutathione levels.
The post Heart Attack Byproduct Linked to Brain Inflammation and Cognitive Decline appeared first on Inside Precision Medicine.
Functions and Sensors of Smart Walkers From 2015 to 2024: Scoping Review
Background: Early mobilization and mobility are essential components of the recovery process following surgery and trauma-related hospitalization. In addition to personalized support from physiotherapists and health care professionals, assistive devices such as walkers play a crucial role in facilitating safe and effective mobility. Objective: This scoping review aims to provide a comprehensive overview of the current state of the literature on the design, sensor technologies, and functional applications of smart walkers and to assess the extent to which existing studies reflect clinical use cases. Methods: Peer-reviewed English articles published between 2015 and 2024 were identified by searching PubMed, CINAHL, SSCI, and IEEE, focusing on the topic of smart walkers. Secondary analyses and walkers with 2 wheels or fewer were excluded in abstract screening. Study screening and selection were performed according to the Joanna Briggs Institute guidelines for scoping research and reported following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. The Rayyan systematic review management software was used for study selection. The articles included were analyzed with respect to the sensor technologies used, their functional capabilities, and their application scenarios. Results: Of the 800 articles screened, 44 (5.5%) met the inclusion criteria. Most of these articles were research reports (n=36, 81.8%) and were conducted in laboratory-based environments (n=30, 68.2%). Most studies evaluated smart walkers in asymptomatic populations (n=29, 65.9%), with half (n=22, 50%) involving younger adults. Among the sensor modalities reported, camera-based and light detection and ranging–based sensors were most prevalent for half of the implementations. Light detection and ranging–based sensors can be categorized according to their primary functions: gait analysis (n=11, 25%), collision detection (n=9, 36%), and navigation (n=5, 11.4%). Load sensors (n=10, 22.7%) and ultrasonic sensors (n=11, 25%) were among the most frequently cited sensor modalities in the literature. Load sensors, also known as force sensors, are integrated into the handlebars, frame, forearm supports, or chest pads of smart walkers. These sensors measure the user’s load, providing essential data for calculating body weight support or inferring the user’s intention to move. Conclusions: The smart walkers described in the literature were predominantly tested in asymptomatic and younger populations. Bridging the gap between current laboratory-based research and real-world clinical environments, as well as the daily lives of end users, remains a critical objective. Addressing the specific needs of older adults through comprehensive requirements analyses and iterative testing continues to be an ongoing challenge, yet these processes can serve as integral components of research and development projects. Trial Registration: OSF Registries osf.io/ctpf4; https://osf.io/ctpf4
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