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Imagery Control Therapy and Lucid Dreaming for REM-Related Symptoms in Narcolepsy

Conditions: Narcolepsy Type 1; Hypnagogic Hallucinations; Sleep Paralysis; REM Sleep Intrusion Symptoms; Central Disorders of Hypersomnolence

Interventions: Behavioral: Cognitive Behavioral Therapy for Narcolepsy (CBT-NAR) With Lucid Dreaming and Imagery Control Therapy; Behavioral: Sleep Hygiene Education and Structured Clinical Follow-up

Sponsors: Institute of Behavioral Sleep Medicine, Colombia

Completed
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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.

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<![CDATA[FDA clears Modius Spero headset, a noninvasive at-home neuromodulation therapy that eases PTSD symptoms, with veterans first to access via VA.]]>
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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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