ObjectiveTo observe the clinical effect of transcutaneous auricular vagus nerve stimulation (taVNS) in drug-refractory paroxysmal sympathetic hyperactivity (PSH).MethodsThis case report describes the clinical course of a 63-year-old male with PSH following intracerebral hemorrhage. PSH episodes were characterized by tachypnea, tachycardia, hypertension, and increased muscle tone. After 2 weeks of combination pharmacotherapy (propranolol, baclofen, gabapentin), blood pressure, heart rate, and muscle tone improved, but tachypnea remained inadequately controlled. Although sedative agents alleviated tachypnea, they led to decreased consciousness level and could not be continued. Subsequently, taVNS was added to the ongoing pharmacotherapy.ResultsAfter 4 weeks of taVNS treatment, PSH episode frequency and tachypnea improved. Baclofen and gabapentin were discontinued, propranolol dosage was reduced, and the patient’s consciousness level showed improvement. After another 4 weeks of continued treatment, only mild tachypnea occurred occasionally under strong stimulation, without other sympathetic symptoms. Consciousness level further improved.ConclusionThis case suggests that taVNS may be a safe adjunctive intervention option for drug-refractory PSH. The symptom relief and consciousness improvement observed during treatment may be related to the application of taVNS.
Functional methods for evaluating the efficacy of retinal optogenetic therapy for vision restoration
Optogenetic therapy is a promising strategy for vision restoration. Functional assays have an important role in assessing the modulation of neural activity in response to light stimulation. Each functional assay needs to be carefully considered and evaluated for the preclinical development of optogenetic approaches to work toward meaningful vision restoration. Each strategy contributes to understanding the efficacy of vision restoration and the physiology of retinal optogenetic therapy. At a molecular level, bioluminescence resonance energy-transfer based and G protein coupling assays can be used. Calcium imaging provides measurements with useful spatial and temporal resolution using fluorescent calcium indicators at the cellular level. Electrophysiological tests can include ex vivo recordings by patch-clamping at single-cell resolution, multielectrode array recordings at the network level, and in vivo recordings at the lateral geniculate nucleus and cortical levels. Behavioural tests such as light avoidance, optomotor response and visual discrimination assess functional restoration in vivo. In this review, each functional assay is discussed in the context of retinal optogenetic therapy with notable examples that have demonstrated vision restoration. The advantages, disadvantages, and limitations of each assay are critically compared to highlight their relative scientific value and applicability across different stages of development. This provides insight into how these methods can be integrated within a translational framework, from molecular validation to behavioural outcomes, to better inform the design of preclinical studies. As clinical trials in optogenetic therapy continue to expand, improved alignment between preclinical functional assays and clinically meaningful endpoints will be essential to maximise translational success.
Speech recognition performance with dual-microphone audio processors in mandarin-speaking cochlear implant users
BackgroundCochlear implant (CI) audio processor upgrades have demonstrated speech recognition benefits in non-tonal language populations, but high-level evidence for native Mandarin-speaking CI users (a tonal language with unique signal processing requirements) remains critically limited. This study aimed to assess the speech perception performance of the SONNET 2 and RONDO 3 dual-microphone audio processors in native Mandarin-speaking CI users.MethodsThis prospective single-subject repeated-measures study enrolled 51 native Mandarin-speaking CI users. Speech recognition performance was tested across five processor configurations: the legacy baseline processor, SONNET 2 (S2) in omnidirectional (S2.OMNI) and adaptive intelligence (S2.Adaptive) modes, and RONDO 3 (R3) in omnidirectional (R3.OMNI) and adaptive intelligence (R3.Adaptive) modes. Outcome measures included monosyllabic words, disyllabic words, and sentence recognition in quiet, and sentence recognition in co-located speech-shaped noise (S0N0 paradigm). The pre-specified primary endpoint was sentence recognition in noise for S2.OMNI vs. the legacy processor; confirmatory linear mixed-effects models (LMMs) and subgroup analyses were exclusively performed for the primary endpoint, with pairwise comparisons for all secondary exploratory endpoints.ResultsIn quiet, all four upgraded configurations yielded significantly higher monosyllabic word recognition scores vs. the legacy baseline (all p < 0.05, FDR-adjusted); all configurations except R3. Adaptive showed significant improvements in disyllabic word recognition (all p < 0.05, FDR-adjusted). In the S0N0 noise condition, S2.OMNI and R3.OMNI significantly enhanced sentence recognition vs. the legacy processor (p < 0.001 and p = 0.011, respectively, FDR-adjusted), while no significant benefit was detected for either adaptive mode after FDR correction. LMM analysis confirmed that upgrading to the S2.OMNI configuration was an independent positive predictor of noise sentence recognition (F = 9.885, p = 0.003), with consistent significant benefits across pediatric/adult and unilateral/bilateral users in pre-specified subgroup analyses.ConclusionThis study provides confirmatory evidence that upgrading to the S2.OMNI configuration significantly improves sentence recognition in noise in native Mandarin-speaking CI users, with consistent benefits across key clinical subgroups. Exploratory analyses show that the S2 and R3 processors also deliver significant improvements in word recognition in quiet, These results fill a critical evidence gap for tonal language CI populations and may help guide clinical device selection.
Intracerebroventricular diphtheria toxin causes off-target toxicity in CD11b-DTR and wild-type mice, revealing limitations of DTR-based depletion studies
Diphtheria toxin receptor (DTR)–based depletion models are widely used to study microglial and macrophage function, yet the extent to which diphtheria toxin (DT) produces off-target effects remains incompletely defined. Here, we examined tolerability, behavioural outcomes, and cellular responses following intracerebroventricular (i.c.v.) DT administration in wild-type (WT) and CD11b-DTR mice. Mice received bilateral i.c.v. infusions of DT or vehicle over a 10-day period and were assessed for survival, motor and cognitive behaviour, myeloid cell changes, and neuropathology. Unexpectedly, DT induced dose-dependent mortality in WT mice, demonstrating that toxicity can occur independently of DTR expression. CD11b-DTR mice exhibited greater susceptibility, with reduced survival and the emergence of illness at lower DT doses. Behavioural testing revealed significant dose-dependent impairments in rotarod performance and Y-maze spontaneous alternation in both genotypes, while open-field mobility was largely preserved among animals. Region-specific analysis of myeloid cells in CD11b-DTR mice showed robust depletion in the midbrain at higher DT doses, whereas hippocampal cell numbers remained unchanged with marked morphological signs of activation. These findings indicate that DT-mediated myeloid cell responses vary across brain regions, potentially reflecting differential toxin exposure following ventricular delivery. Consistent with this, focal abnormalities in the brain—including ventriculitis, meningoencephalitis and spongiotic changes—were observed in a subset of clinically affected DT-treated animals, whereas peripheral organs were largely unremarkable and haematological changes were infrequent. Together, these data demonstrate that i.c.v. DT administration can induce mortality, behavioural dysfunction, and focal CNS pathology in both WT and CD11b-DTR mice, with transgene expression amplifying susceptibility. Our findings highlight the need for careful dose optimisation, appropriate DT-treated controls, and cautious interpretation of behavioural phenotypes when employing this model.
Cortical activity during cognitive and walking tasks in individuals with chronic nonspecific low back pain: a functional near-infrared spectroscopy study
IntroductionPrevious research demonstrates that individuals with chronic nonspecific low back pain (CNSLBP) exhibit changes of gait patterns. However, the neural mechanisms responsible for these adverse events remain unelucidated. In this study, we used functional near-infrared spectroscopy (fNIRS) to investigate cortical activities during cognitive and walking tasks to provide evidence of the central mechanisms responsible for changes of gait patterns in individuals with CNSLBP.MethodsIn this cross-sectional study, we evaluated 18 individuals with CNSLBP (the CNSLBP group) and 18 healthy controls (the HC group) under three specific conditions: Task 1 (a single walking task), Task 2 (a single cognitive task) and Task 3 (a cognitive-walking dual task). Cortical activities were measured using fNIRS, including the bilateral premotor cortex and supplementary motor area (PMC/SMA), primary motor cortex (M1), somatosensory association cortex (SAC), and primary somatosensory cortex (S1). Gait parameters, including step duration, step length, stride length, velocity, cadence, swing power, and cycle, were measured using a three-dimensional gait analysis system.ResultsIn Task 1, the CNSLBP group exhibited a significantly lower velocity (p = 0.029) and higher activation in the left SAC (p = 0.001) and right S1 (p = 0.018) than that of the HC group. In Task 2, the CNSLBP group exhibited higher activation in the left SAC (p = 0.028), right SAC (p = 0.033), and left S1 (p = 0.032). In Task 3, the CNSLBP group exhibited significantly lower step length (p = 0.031), stride length (p = 0.041), velocity (p = 0.016), and swing power (p = 0.047). Correlation analysis in Task 1 revealed stronger associations between parameters in the CNSLBP group.ConclusionOur findings suggest that individuals with CNSLBP exhibit distinct patterns of cortical activities and gait performance. The SAC and S1 were involved in walking, and central sensitization was observed in individuals with CNSLBP in daily cognitive and walking tasks. These findings could contribute to the recovery and rehabilitation of CNSLBP.
Psychiatric comorbidities and sexual health risks in HIV-serodiscordant heterosexual couples involving women with borderline personality disorder: a mixed-method study and theoretical modeling
BackgroundHIV-serodiscordant heterosexual couples consist of one partner who is HIV-positive and the other who is HIV-negative. Our previous studies found that the HIV-negative female partner in no-prevention couples (NPC) may be affected by borderline personality disorder (BPD) and might have a history of child abuse, trauma, and neglect. These couples provide valuable insights into public health, particularly regarding health behaviors and psychosocial factors that influence the relationship between psychopathology, illness behaviors related to borderline personality disorder, and the transmission of sexually transmitted diseases.Population and methodsThis study was conducted in three sequential phases. Phase One involved a cross-sectional, multicenter, anonymous survey of 175 HIV-serodiscordant couples, aimed at assessing preventive sexual behaviors. Participants reported sexual protection use during at-risk sexual encounters on a scale ranging from 0% (‘never’) to 100% (‘always’). Phase Two, which constitutes the core of the present investigation, employed qualitative, unstructured interviews and narrative analysis with HIV-negative female partners in serodiscordant relationships. The analytic focus was on identifying patterns of psychopathological comorbidity and health-related behaviors. Through iterative narrative synthesis and thematic coding, the presence of Borderline Personality Disorder (BPD) emerged consistently across cases. The confirmation of BPD as a clinical diagnosis was thus an outcome of this phase, derived from converging narrative indicators and psychopathological profiles rather than a pre-established inclusion criterion. Phase Three, drawing on the findings from both preceding phases, involved developing a theoretical model of the observed behavioral patterns. Integrating quantitative trends from Phase One with the qualitative insights from Phase Two, we developed a conceptual framework to explain the interaction between BPD-related psychopathology, relational dynamics, and HIV (or other sexually transmitted diseases) risk behaviors. This model aims to guide future healthcare strategies for HIV-negative women with BPD in serodiscordant relationships, a group identified as particularly vulnerable to sexually transmitted HIV due to compromised primary prevention.ResultsSpecific health belief models and behaviors related to health emerged among HIV-negative female partners with BPD who decline prevention during behaviors that put them at risk for HIV sexual transmission in stable relationships with HIV-positive males. Results illustrate that women with BPD who have a history of child abuse and trauma often exhibit comorbid self-defeating personality disorder (SDPD), dependent personality disorder (DPD), and complex post-traumatic stress disorder (CPTSD). We could not replicate similar findings in HIV negative males.ConclusionsThe current study confirms that health behaviors and women’s health may be influenced by underlying personality, behavioral, and psychosocial factors, which public health policymakers must address to improve primary prevention of transmissible diseases. We suggest that child abuse, neglect, and trauma may be connected to overlooked health behaviors across a person’s entire life span.
Psychological function in the context of protracted stress during war: a multi-sample, multivariate longitudinal study
Continuous traumatic stress has wide-ranging implications for important life outcomes across multiple domains. We present the design protocol from the first waves of one of the most comprehensive studies of the impact of one pervasive continuous traumatic stress context—war—on individuals. In this ongoing project we have been collecting quantitative and qualitative data on psychological function, risk, and resilience at different levels of influence and at various junctures during the ongoing 2023–2025 Hamas-Israel war from three samples (total N = 16,330). We present this large-scale, multi-sample, multivariate, mixed-method, longitudinal study, and showcase select, preliminary findings at different levels of analysis and in different samples (e.g., concerning war exposure, trust in institutions, and well-being). We document the design, scope, and future trajectory of the project, encouraging interdisciplinary, cross-border collaborations among researchers across diverse fields. This is important not only for understanding responses to the current conflict, but also for understanding risk and resilience in other conflict-affected regions and among populations facing continuous traumatic stress more broadly.
Cyclothymic and anxious affective temperament in perinatal depression: findings from an exploratory cross-sectional study
IntroductionThe perinatal period represents a vulnerable period in which women may experience high psychic distress due to psychological, biological and social changes. The prevalence of perinatal depression (PND) is estimated around 15%-20% during pregnancy and 16%-18% after childbirth. Although several risk factors have been investigated in the PND development, few studies explored the role of affective temperaments, well known to exert a role in any mood disorders. The aim of our study was to explore which is the most represented affective temperamental profile in PND as well as which is its role in the development and severity of depressive symptoms during perinatal period.MethodsAll pregnant women admitted at the Perinatal Mental Health Outpatient Service, Unit of Clinical Psychiatry, University Hospital of Marche, Polytechnic University of Marche, Ancona, Italy, between April 2021 and July 2025, were screened for PND through Edinburgh Postnatal Depression Scale (EPDS) and a semi-structured clinical interview (SCID-5-CV). Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-M) was administered to all pregnant women. ResultsThe PND prevalence was 33.1%. PND was significantly associated with higher cyclothymic (B = 0.356, p = 0.001) and anxious TEMPS-M scores (B = 0.247, p = 0.026) and a positive psychiatric history (B = 5.245, p < 0.001) (R = 0.6, R2 = 0.36, F(3,129) = 24.189, p < 0.001). Logistic regression indicated that cyclothymic (Exp(B)=1.118, p=0.008), hyperthymic (Exp(B)=0.911, p=0.049), anxious temperaments (Exp(B)=1.109, p=0.029), presence of medical comorbidities (Exp(B)=0.224, p=0.003) and psychiatric history (Exp(B)=5.144, p=0.001) were independent predictors of PND.DiscussionAffective temperaments, particularly cyclothymic and anxious profiles, and prior psychiatric history are predictors of perinatal depression. Incorporating temperament assessment alongside standard screening tools such as the EPDS may improve early identification of women at risk, supporting tailored preventive and therapeutic strategies.
Auditory processing and communication in autism: exploring verbal abilities and vocal affective cues
This study examined the role of auditory processing in autism spectrum disorder, focusing on its association with verbal and non-verbal vocal communication skills in children and adolescents. A total of 97 English-speaking autistic participants (ages 7.9–17.4 years, mean = 12.3) and 44 neurotypical peers (ages 8.4-16.8, mean= 12.3) completed assessments of auditory processing and communication skills. We analyzed the relationships between scores on the SCAN-3 Tests for Auditory Processing Disorders time-compressed sentences, auditory figure-ground (+ 8dB), gap detection, and competing words-free recall subtests, the Clinical Evaluation of Language Fundamentals-Fifth Edition (CELF-5) expressive and receptive language indices, the Goldman-Fristoe Test of Articulation-3rd Edition (GFTA-3) Sounds-In-Words subtest, and the Diagnostic Analysis of Nonverbal Accuracy-2nd Edition (DANVA-2) paralanguage subtests. Measures of auditory processing were associated with both verbal and non-verbal communication skills in the autistic participants. Specifically, we found that SCAN-3 time-compressed sentence and gap detection scores were associated with expressive and receptive language skills, receptive vocabulary scores, and ability to recognize vocal emotional cues. Gap detection abilities additionally correlated positively with expressive and receptive language skills, while auditory figure-ground task performance was related to articulation. In conclusion, this study suggests specific aspects of auditory processing may be important for development of specific aspects of auditory communication skills in children on the spectrum. Specifically, spectral aspects of auditory processing abilities were associated with articulation accuracy whereas temporal components of auditory processing may impact broader verbal and nonverbal communication skills. Further research is needed to better understand the underlying mechanisms of these associations and potential directions of causality to inform development of interventions that target auditory processing and auditory communication skills in ASD.
Association between the geriatric nutritional risk index and postoperative delirium: a meta-analysis
BackgroundMalnutrition has been suggested as an important contributor to postoperative delirium (POD). The geriatric nutritional risk index (GNRI), a simple indicator based on serum albumin and body weight, has been increasingly evaluated in surgical patients. This meta-analysis aimed to clarify the association between GNRI and the risk of POD.MethodsPubMed, Embase, and Web of Science were searched for observational studies evaluating the association between categorized GNRI and POD. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models accounting for heterogeneity.ResultsTwelve cohort studies involving 12,332 surgical patients were included. Overall, low GNRI was associated with a significantly increased risk of POD (RR = 1.62, 95% CI: 1.34–1.96; I² = 27%). Subgroup analyses showed a stronger association in studies with mean patient age > 74 years compared to ≤ 74 years (p for subgroup difference = 0.02) and in those using GNRI cutoffs < 98 compared to ≥ 98 (p = 0.04). The association was weaker in studies using multivariate analyses compared with univariate analyses (p = 0.01). Meta-regression indicated that GNRI cutoff values significantly influenced the pooled effect (p = 0.04). The funnel plot showed mild asymmetry, whereas Egger’s test was not significant (p = 0.11), and trim-and-fill analysis produced a similar pooled estimate (RR = 1.54, 95% CI: 1.26–1.87).ConclusionsLow GNRI is associated with an increased risk of POD in surgical patients, suggesting that preoperative nutritional assessment may help identify individuals at higher risk for this complication.Systematic Review RegistrationThe study protocol was registered prospectively in the PROSPERO database (registration number: CRD420261335609).