Ashwagandha (Withania somnifera), as an important herbal medicine, has been increasingly recognized for its role in mental health management, particularly in reducing stress and anxiety, and reflects the growing relevance of complementary and alternative medicine in addressing psychological well-being. The present study aims to investigate its effectiveness by pooling the evidence from existing randomized controlled trials (RCTs).

Major medical databases of PubMed, Scopus, and Web of Science Core Collection were searched. Eligible studies were included. Meta-analysis, meta-regression, non-linear dose-response analysis, and subgroup analyses were conducted. Standardized mean differences (SMDs) were calculated. P-values < 0.05 were considered as statistically significant. The study protocol was registered in the PROSPERO database (CRD420251073134).

Twenty-two studies met the eligibility criteria and were included. Meta-analysis revealed that supplementation with ashwagandha significantly improves stress (SMD = -5.88; 95% CI: -8.15 to -3.60), depression (SMD = -5.68; 95% CI: -8.43 to -2.94), and anxiety (SMD = -6.87; 95% CI: -8.77 to -4.97). There was significant linear (coefficient = 0.005, P = 0.031) and non-linear (P-nonlinearity = 0.005) association between dosages of administered ashwagandha and stress levels.

Current evidence suggests that ashwagandha supplementation holds promising potential in alleviating symptoms of stress, anxiety, and depression. However, to strengthen these findings and translate them into clinical recommendations, well-designed, high-quality trials are still needed to address existing heterogeneity and to establish the most effective dosages and intervention durations.

The study of sex/gender (S/G) differences in neuroscience, particularly in emotional processing, has been hindered by methodological inconsistencies, often producing biased conclusions that overgeneralize brain differences between males and females. Moreover, many studies fail to consider how other sociodemographic factors interact with S/G to influence the brain. This study aims to address these gaps by investigating whether potential S/G effects in brain activation during emotion-evoking functional magnetic resonance imaging (fMRI) tasks are influenced by those factors.

This meta-analysis followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and was registered on PROSPERO. We searched for peer-reviewed studies on S/G differences in whole-brain activations during fMRI emotion-evoking tasks. Data analysis was conducted using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI). Subgroup analyses were performed based on the type of tasks and on race, and meta-regressions assessed the impact of age, education, and hormonal contraceptive use on the main effects.

63 studies were included for the meta-analysis, comprising a total of 5,436 individuals from the general population (2,635 females). The main meta-analysis showed no significant S/G activation differences at the whole-brain level. Subgroup analyses, however, revealed significant S/G differences depending on the type of task and the race subgroup, while meta-regression analyses showed significant associations between S/G effects and education and hormonal contraceptive use, with notable shifts in activation patterns across these variables.

Our findings highlight the need for more complex, intersectional models that consider the dynamic interplay of biological, psychological, and social factors in shaping S/G differences in brain function and mental health.

Neural organoids are invaluable model systems for studying neurodevelopment, generated by either guided or unguided approaches. Despite the importance for the field, the resulting differences between these models are unclear. To obtain an unbiased comparison, we performed a multi-omic analysis of forebrain organoids generated in parallel with two widely applied guided and unguided protocols. The guided forebrain organoids contained a larger proportion of neurons, including GABAergic interneurons, whereas the unguided organoids contained significantly more choroid plexus, radial glia, and astrocytes at later stages. Substantial differences in metabolic profiles were identified, pointing to increased levels of oxidative phosphorylation and fatty acid β-oxidation in the unguided forebrain organoids and a higher reliance on glycolysis in the guided forebrain organoids. Overall, our study comprises a thorough description of the multi-omic differences between these guided and unguided forebrain organoids and provides an important resource for the neural organoid field studying neurodevelopment and disease.

Human dermal sleeping nociceptors display ongoing activity in neuropathic pain, affecting 10% of the population. Despite advances in rodents, a molecular marker for these mechano-insensitive C-fibers (CMis) in human skin remains elusive, preventing targeted therapy. Using a Patch-seq approach, we combined single-cell transcriptomics, following electrophysiological characterization, with single-nucleus and spatial transcriptomics from pigs and integrated our findings with cross-species and human transcriptomic data. We functionally identified CMis in pig sensory neurons with patch clamp, using adapted protocols from human microneurography. We identified oncostatin M receptor (OSMR) and somatostatin (SST) as marker genes for CMis. Following dermal injection in healthy human volunteers, oncostatin M, the ligand of OSMR, exclusively modulates CMis. Our findings characterize the molecular architecture of human dermal sleeping nociceptors, providing a framework for mechanistic insight into neuropathic pain and potential therapeutic strategies.

Isolated rapid eye movement sleep behavior disorder (iRBD) is a prodromal stage of α-synucleinopathy such as Parkinson's disease (PD). Brain cholinergic alterations have been reported in these diseases, but direct comparisons of terminal density between iRBD and clinically manifest PD have not yet been performed.

To assess brain cholinergic terminal density in iRBD using positron emission tomography (PET) with [¹⁸F]-fluoroethoxybenzovesamicol (FEOBV), and to compare findings with both healthy controls and patients with PD.

Forty-six participants (16 with polysomnography-confirmed iRBD, 12 with PD, and 18 controls) underwent high-resolution PET neuroimaging with FEOBV. Voxel-wise analyses and effect size mapping were conducted to compare the groups, using standardized uptake value ratios (SUVRs). Correlations were performed between whole-cortex SUVR and clinical measures.

Compared to controls, both the iRBD and PD groups exhibited significant cortical cholinergic denervation of similar magnitudes (11-12 %). Effect size mapping revealed very large losses (Cohen's ds < -1.5) in the posterior cortex in both patient groups, predominantly occipital-parietal in iRBD and occipital-temporal in PD. In iRBD, lower cortical uptake was associated with poorer performance on executive and visuospatial tests. Moreover, in iRBD but not in PD, there was a trend toward higher FEOBV uptake in subcortical areas, including brainstem regions.

Cholinergic denervation in iRBD is comparable in extent to that in PD, with subtle topographic distinctions, and correlates with cognitive deficits.

This study used different metrics to assess the reliability of radiology text and images in Distal Radial Fractures (DRF) classifications using classifiers with varying levels of experience.

A random sample of 534 patients (16 + years) admitted to two major trauma centres for > 24 h for DRF management with 1,269 radiology images and radiology text reports were reviewed. Eight classifiers, with varying levels of experience, were randomly assigned patients, with overlap, to classify four different DRF classifications, nine radiological features and one treatment type: (two interns (802 text/images), three registrars (1,079 text/images), three orthopaedic trauma specialists (740 text/images)). The agreement measures utilised were: Percentage agreement (PA), Brennan/ Prediger coefficient, Cohen/Conger Kappa, Fleiss kappa, Gwet's AC, Krippendorff's alpha coefficient; all with 95% confidence intervals.

For DRF classifications, the ulnar fracture (81%, 77%-86%) then AO Level 1 (67%, 60%-74%) had the highest PA; AO Level 3 had the lowest (29%, 23%-34%). For radiological features: highest PA was the presence/absence of tear drop/volar rim fragment (97%, 96%-98%) and severe dorsal comminution (97%, 96%-98%); lowest was ulnar variance (70%, 57%-83%). Treatment had high PA (96%, 87%-100%). Differences across classifier experience were not significant.

Even with descriptive texts from the radiology reports and x-ray images, DRF classification is complex and classifier experience not affecting classification. Generally, above fair agreement and interrater reliability was achieved, but the type and complexity of the classification task and the choice of agreement coefficient were important considerations in the reporting of agreement and reliability of the data.

Depressive disorders and asthma frequently co-occur in adolescence, but global co-patterning and shared population-level risk signals remain unclear.

Using Global Burden of Disease (GBD) 2021 estimates for ages 10-19 years (1990-2021), we characterized global and China-specific trends and sex disparities in incidence, prevalence, and disability-adjusted life years (DALYs) using joinpoint regression. We constructed a 2021 incidence-quartile co-occurrence typology, estimated typology-stratified coupling (Spearman rank correlation coefficient, ρ) using pooled country-year observations (1990/2000/2011/2021), prioritized shared summary exposure value (SEV) correlates using Shapley additive explanations (SHAP)-informed multiclass random forests and negative binomial models, and evaluated bidirectional genetic directionality using two-sample Mendelian randomization (MR).

The burden of depressive disorders remained broadly stable but started to increase from 2019 onward, with persistent female excess. Asthma DALY rates declined overall, whereas incidence and prevalence were largely stable globally, with modest recent increases in North America. In 2021, typology membership showed marked income gradients and positive within-typology coupling (ρ = 0.408-0.925). Ambient particulate matter ≤2.5 μm (PM2.5) and household air pollution from solid fuels were consistently prioritized as shared ecological correlates and showed marked socioeconomic gradients. Two-sample MR supported a modest depressive disorders-to-asthma signal (inverse-variance weighted (IVW) odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.02-1.36), whereas reverse-direction estimates were weaker and more heterogeneous.

Adolescent depressive disorders and asthma exhibit divergent long-term trajectories but cluster into income-patterned co-occurrence typologies with shared ecological risk signals. These findings reflect population-level correlates and do not directly estimate intervention or policy effects.

Circadian rhythms are key determinants of physical and mental health at the nexus of physiology and behavior. Classically, endogenous circadian rhythms are characterized according to three principal dimensions: circadian phase, amplitude and stability. From a behavioral perspective, the timing and regularity of nychthemeral behaviors represent two additional dimensions, and we propose as a sixth dimension the sleep complaints arising from a circadian disruption due to a mismatch between circadian physiology and nycthemeral behaviors. This article reviews each of these dimensions and examines their interactions, along with their effects on sleep and health. On this basis, we propose an integrated definition of circadian health. We then review both, objective (melatonin, temperature, actimetry) and subjective (sleep diaries, self-report questionnaires) tools for assessing each of the circadian health dimensions. Finally, we propose a novel tool aimed at assessing those circadian health dimensions as well as the computation of a composite index to quantify circadian health, along with a graphical representation to visualize it. While further validation is still needed, this proposal will help clinicians and researchers better decipher circadian rhythms and their impact on mental and physical health and may offer new opportunities for public health promotion in both general and clinical populations.

Recently, the effectiveness of noninvasive brain stimulation (NIBS) techniques, such as transcranial direct current stimulation (tDCS), has been shown in psychiatric disorders. Here, a new, intensified protocol has been developed, which is suggested to induce late-phase long-term potentiation (LTP)-like plasticity, and increase efficacy of the intervention. In the present case report, we evaluated the effectiveness of a new intensified tDCS protocol (30 sessions, 2 mA for 20 min, 2 sessions daily with a 20 min interval between daily sessions, for 15 d) applied to the left ventromedial prefrontal cortex (AF3 according to the EEG International 10 to 20 system), which is suggested to induce late-phase plasticity, and therefore is expected to have superior clinical effects, in a girl with severe cockroach phobia. Severity of phobia symptoms, the anxiety level to phobic stimuli (cockroach), general anxiety, depression, and emotional distress were measured before and immediately after intervention and at follow-up (3 wk and 6 wk after the last intervention). The results show a significant improvement in phobia symptoms postintervention, maintained for up to 6 weeks after the last intervention, and side effects, including burning sensations and skin redness, were mild. These findings suggest that an intensified tDCS stimulation protocol over the left vmPFC may effectively improve phobia symptoms. Moreover, the results showed that this intensified protocol is safe and tolerable. To substantiate the effects of the current protocol, further investigations in larger patient groups are required.