The dorsomedial hypothalamic nucleus and perifornical area (DMH/PeF), historically identified as the hypothalamic defence area, plays a key role in orchestrating autonomic and respiratory adjustments during threat-related states. To investigate how activation of this region affects upper-airway and respiratory motor circuits, we examined its anatomical and functional interactions with laryngeal-related medullary nuclei using combined immunohistochemical mapping and physiological recordings in spontaneously breathing anaesthetised rats. Neuronal activation was assessed using c-Fos immunohistochemistry (c-Fos-ir) combined with ChAT and FoxP2 labelling to identify motoneurons and non-motoneuronal populations across the compact, semicompact and loose formations of the nucleus ambiguus (nA), as well as within the nucleus retroambiguus (nRA), during DMH/PeF electrical stimulation. Hypothalamic activation produced a clear subdivision-specific recruitment in the nA, with significant ipsilateral increases in c-Fos-ir within the semicompact (motoneurons, p < 0.001; non-motoneurons, p < 0.05) and compact formations (non-motoneurons, p < 0.05). The nRA also exhibited robust ipsilateral activation (non-motoneurons, p < 0.001). FoxP2-positive neurons remained stable across groups, indicating that FoxP2 reflects neuronal phenotype rather than acute activation. A second set of experiments evaluated the functional impact of electrical and chemical (glutamate) DMH/PeF activation on subglottic pressure, an index of laryngeal resistance. Both stimulation modalities produced a marked reduction in subglottic pressure (p < 0.001 and p < 0.01), accompanied by a reproducible autonomic–respiratory pattern characterised by tachypnoea, tachycardia and a pressor response. Overall, our results provide new insight into how hypothalamic circuits regulate subglottic pressure and laryngeal activity, suggesting that DMH/PeF activation is associated with the recruitment of specific nA and nRA domains, which may contribute to the adjustment of upper-airway patency during defensive responses.
Safety of transcutaneous electrical stimulation potentiating recovery in acute spinal cord injury syndromes: a trial protocol
Background and objectivesSpinal cord injury (SCI) often results in permanent paralysis, leading to substantial long-term disability and loss of quality-adjusted life years. Strategies to preserve neural function in the hyperacute phase are needed. Transcutaneous spinal cord stimulation (tSCS) improves neurological function in chronic SCI. Earlier implementation in acute SCI may preserve or restore function and improve recovery.MethodsSTEP-RAISE is a Phase 1/2 prospective clinical trial evaluating the safety and preliminary efficacy of tSCS in acute moderate-to-severe traumatic SCI. Electrical current will be delivered to the lumbosacral spinal cord using the investigational ARC-Ex device (ONWARD Medical) via surface electrodes over the thoracolumbar region. Phase 2 is a randomized, triple-blinded, placebo-controlled trial designed to assess treatment effects. Safety outcomes include hemodynamics, spinal cord perfusion pressure, and skin reactions. Efficacy will be assessed using the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) examination with electromyography at baseline, during stimulation, and at 6-month follow-up. Biomarkers include neuronal (UCH-L1) and glial (GFAP) markers and exploratory proteomics in blood and cerebrospinal fluid collected prior to stimulation and at discharge.DiscussionThe STEP-RAISE trial evaluates safety and preliminary efficacy of non-invasive tSCS initiated within 72 h of SCI to improve sensorimotor recovery. Neurophysiological and patient-reported outcomes will characterize recovery and assess whether early tSCS augments functional recovery. This study is designed to estimate treatment effects and inform subsequent trials in acute SCI. Planned enrollment includes 5 participants in Phase 1 and 10 in Phase 2.Clinical trial registrationClinicalTrial.gov: NCT07090473; first posted on 07/29/2025, first open to enrollment 04/2026. https://clinicaltrials.gov/study/NCT07090473
Using cortical auditory-evoked potential responses to verify the objective benefit of aural rehabilitation in adult cochlear implant users
IntroductionCortical auditory-evoked potential (CAEP) responses are used clinically to assess auditory processing and support cochlear implant (CI) mapping procedures post-implantation. This study aims to examine CAEP responses as an objective measure of neurophysiological changes following a structured Aural Rehabilitation Program (ARP) in long-term adult CI users, with poor baseline speech perception performance. Advancing our understanding of the mechanisms underlying improved post-implantation outcomes in poor performing CI users may inform the development of targeted interventions and refinement of evidence-based rehabilitation strategies.MethodsAdult unilateral CI users with post-lingual deafness were recruited for an intensive clinician-directed ARP incorporating structured active listening exercises. The ARP consisted of weekly 1-h face-to-face sessions over 10 weeks with repeated assessments at baseline (T0) and 10-week intervals (T10, T20, T30). Participants were allocated to immediate (Group 1), 10-week delay (Group 2), or 20-week delay (Group 3) ARP groups, while a control group completed assessments without intensive ARP. Speech perception in quiet [CNC phoneme and word scores (%)] and electrically-evoked CAEP (eCAEP) response [P1-N1-P2 peak latencies (ms) and amplitudes (μV)] measures were collected at each time point for all groups. The repeated measures design incorporated staggered pre- and post-ARP periods for Groups 1–3 (T0-T10, T10-T20, and T20-T30, respectively). CNC and eCAEP measures were analyzed pre- and post-ARP intervention and across assessment intervals (T0-T30) to evaluate rehabilitation effects and account for natural variability and potential ongoing adaptation in auditory performance over time, independent of ARP-related changes.ResultsNo significant changes were observed in eCAEP response latencies or amplitudes from pre- to post-rehabilitation. However, the ARP intervention group demonstrated significantly higher CNC phoneme and word recognition scores compared to the control group in both implant-alone and binaural listening conditions post-rehabilitation.DiscussionNo measurable neurophysiological changes were observed in eCAEP responses from pre- to post-rehabilitation. However, the ARP intervention group demonstrated behavioral improvements, reflected in marginal increases in speech perception scores at both phoneme and word recognition levels, which were not observed in the control group. These findings highlight the clinical value of structured aural rehabilitation in supporting improved outcomes for long-term adult CI users with poor baseline performance.
Mechanisms underlying the association between perceived recurrence risk and negative emotions in patients with ischemic stroke: a cross-sectional study
ObjectiveTo examine the relationships among perceived risk of recurrence, attitudes toward seeking professional psychological help, negative emotions, and family care in patients with ischemic stroke, and to test a moderated mediation model. The findings aim to provide a scientific basis for optimizing clinical psychological interventions and family support strategies.MethodsA cross-sectional survey was conducted among 311 patients with ischemic stroke recruited from three tertiary hospitals in Sichuan Province, China. Data were collected using validated scales measuring perceived recurrence risk, help-seeking attitudes, negative emotions, and family care. Mediation and moderated mediation analyses were performed using SPSS 27.0 and PROCESS macro (Models 4 and 58), with 5, 000 bootstrap resamples to estimate 95% confidence intervals (CIs).ResultsPerceived recurrence risk was positively associated with negative emotions (β = 0.350, p < 0.001). Attitudes toward seeking professional psychological help partially mediated this association, with a significant indirect effect (effect = 0.131, 95% CI: 0.082–0.192), accounting for 40.68% of the total effect. Family care moderated both paths of the mediation model. In the first stage, family care moderated the association between perceived recurrence risk and help-seeking attitudes (β = 0.043, p = 0.001), such that higher family care weakened the negative association. In the second stage, family care moderated the association between help-seeking attitudes and negative emotions (β = −0.075, p = 0.008), indicating that higher family care strengthened the protective association between help-seeking attitudes and lower negative emotions.ConclusionPerceived recurrence risk, help-seeking attitudes, and negative emotions are significantly associated in patients with ischemic stroke. Help-seeking attitudes partially explain this association, while family care plays a significant moderating role in both stages. These findings highlight the importance of psychological and family-centered support in stroke rehabilitation. However, causal interpretations should be made cautiously due to the cross-sectional design.
A conceptual multi-agent architecture for mental health triage in post-conflict Arabic-speaking populations: a theoretical proposition and staged validation argument
Syria’s protracted conflict has produced a mental health crisis of extraordinary scale, with post-traumatic stress, depression, and anxiety estimated at several times global baselines, set against fewer than 0.37 psychiatrists per 100,000 people. Existing AI mental health tools have been developed and evaluated primarily for English-speaking, non-humanitarian populations, and their transfer to this setting is constrained by three simultaneous structural deficiencies—extreme clinical scarcity, Arabic natural-language-processing underperformance for dialect, and cultural misalignment with Syrian idioms of distress—which we term the Triple Gap. This article is a conceptual contribution in the Hypothesis and Theory genre, and its central claim is theoretical rather than technical: that AI-assisted mental-health triage at a safety floor adequate for crisis relevant care in this setting is conditional on the joint satisfaction of three constraints—linguistic adequacy for the local dialect, cultural validity for local idioms of distress and help-seeking, and bounded clinical responsibility through human oversight. These constraints interact, so that a system satisfying fewer than all three is expected to fail in clinically consequential rather than random ways. As one possible design response to this proposition—neither the only one nor a validated one—we describe a conceptual multi-agent architecture aligned with the WHO mhGAP task-shifting model: a four-stage pipeline (screening, risk stratification, routing, follow-up) constrained by a cross-cutting cultural-adaptation layer, augmented by candidate verification mechanisms with explicit abstention, and governed by human oversight in which clinical responsibility rests with a licensed clinician. The proposal is a hybrid clinical decision support hypothesis, not an autonomous system. Because no Syrian Arabic clinical corpus yet exists, the conversational components of the design cannot presently be evaluated; we therefore set out a staged sequencing argument for future work in which the construction of a Syrian Arabic Mental Health Evaluation Corpus (SAMHEC) is the first and rate-limiting condition. We present no prototype, no corpus, and no clinical, cultural, or safety evaluation, and we make no claim of clinical validity, safety, or readiness for deployment. The contribution is the integration of multi-agent triage with task-shifting and cultural adaptation into a single conditional argument whose adequacy can be established only through the staged empirical work we describe.
Editorial: Treatment resistant depression: epidemiology, clinic, burden and treatment, volume II
Effects of visual art therapy on depressive symptoms in adults: a systematic review and meta-analysis
ObjectiveTo systematically evaluate the intervention effects of visual art therapy on depressive symptoms in adults, and to examine its impact on anxiety symptoms.MethodsA systematic search was conducted in databases including CNKI, WanFang Data, VIP, Chinese Biomedical Literature Database (CBM), PubMed, Web of Science, Cochrane Library, and Embase from inception to March 2026. Randomized controlled trials were included in which visual art therapy was used to intervene in depressive symptoms among adults (≥18 years).Meta-analysis was performed using Stata 18.0 software.The primary outcome was depressive symptoms, measured by scales such as the BDI, GDS, HADS-D, and SDS, and the secondary outcome was anxiety symptoms, measured by scales such as the BAI, HADS-A, and SAS. Fixed-effect or random-effect models were selected according to the level of heterogeneity, and subgroup analyses were conducted.ResultsA total of 12 randomized controlled trials involving 741 adults were included, with 377 participants in the intervention group and 364 in the control group.The meta-analysis showed that visual art therapy effectively alleviated depressive symptoms (SMD = -0.81, 95% CI: -1.16 to -0.46, P < 0.00001) and anxiety symptoms (SMD = -0.69, 95% CI: -0.90 to -0.48, P < 0.00001) in adults.Subgroup analyses indicated that interventions with a duration of <12 weeks, <12 sessions in total, and a single-session length of ≤60 minutes were associated with larger effect sizes for the improvement of depressive symptoms; improvements in anxiety symptoms were more pronounced in intervention protocols characterized by higher frequency (>12 sessions), shorter overall duration (≤6 weeks), and shorter single-session length (≤60 minutes).ConclusionAs a non-pharmacological intervention, VAT has potential as an adjunctive approach for alleviating depressive and anxiety symptoms in adults.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261371354, identifier CRD420261371354.
The association between worry, rumination, and metacognitive beliefs in female adolescents with Anorexia Nervosa
BackgroundA growing body of literature has emphasized the role of worry and rumination in eating disorders (EDs). According to the metacognitive model, worry and rumination are maintained by dysfunctional metacognitive beliefs. Although metacognitive beliefs have been investigated in adults with EDs, their role in adolescents with EDs remains underexplored. The present exploratory study aimed to examine the specific association among worry, rumination, and metacognitive beliefs and eating disorder symptomatology in adolescents with AN.MethodsThirty Italian female adolescents (mean age ± SD: 15.387 ± 1.35 years, mean Body Mass Index (BMI): 16.34 ± 2.5 kg/m2) completed a self-report survey composed of the Penn State Worry Questionnaire (PSWQ), the Ruminative Response Scale (RRS), the Metacognitions Questionnaire – 30 (MCQ-30), and the Eating Disorder Inventory – 3 (EDI-3).ResultsThus, Model 1, including RRS and PSWQ, was significant (F = 17.5, p<0.001) and explained 57% of the variance (R² = 0.574). Within this model, RRS was the only significant predictor (p = 0.019) of the Eating Disorder Risk Composite (EDRC) of EDI-3, indicating that higher rumination scores were associated with greater eating disorder symptomatology. Once MCQ was entered as a predictor of EDRC, there was no significant incremental variance compared with Model 2 (ΔR² = 0.0034, p = 0.658), even though the model remained significant overall (F = 11.4, p < 0.001). The final model explained 58% of variance (R² = 0.578; Cohen’s f2 = 1.37).ConclusionRumination was significantly associated with eating disorder symptomatology. Although worry showed strong positive associations with eating disorder symptomatology at the correlational level, it did not maintain an independent role once rumination was included in the regression model. The final model showed a very large effect size (Cohen’s f² = 1.37), suggesting strong associations between predictors and eating disorder symptoms in the present sample. However, this estimate should be interpreted cautiously, given the limited sample size and the exploratory nature of the analysis. Contrary to our expectations, metacognitive beliefs did not significantly explain the variance of eating disorder symptomatology. This finding may reflect the more proximal role of RNT in explaining the variance in eating disorder symptomatology, or alternatively, the possibility that only specific metacognitive domains—rather than overall metacognitive functioning—are relevant in this population.
Governing the social production of care: the hidden foundation of health systems
Nature Medicine, Published online: 22 July 2026; doi:10.1038/s41591-026-04535-y
Health systems rely on unpaid care that is poorly measured and governed. We argue that unpaid care, and the wider social production system behind it, is a productive input whose breakdown drives avoidable admissions, delayed discharge, and labor-force exit. We propose a national accounting framework, a diagnostic lens, and five policy priorities.
FcRH5×CD3 bispecific antibody cevostamab in relapsed or refractory multiple myeloma: a phase 1 trial
Nature Medicine, Published online: 22 July 2026; doi:10.1038/s41591-026-04522-3
In a phase 1 trial, the maximum tolerated dose for an FcRH5-containing bispecific T cell engager was not reached, and there was an encouraging response rate in patients with relapsed or refractory multiple myeloma.