• Distinct and shared neurobiological patterns in PTSD and CPTSD: evidence from resting-state fMRI.
    5 days ago
    Complex Post-Traumatic Stress Disorder (CPTSD) is a diagnosis newly introduced in the ICD-11. However, its status as a distinct disorder from Post-Traumatic Stress Disorder (PTSD) remains debated, and there is a notable lack of neuroimaging evidence derived from resting-state functional magnetic resonance imaging (rs-fMRI) to clarify this distinction. This study aimed to address this gap by providing integrated neuroimaging evidence to elucidate their unique and shared neural bases.

    By collecting resting-state functional brain imaging data from patients with PTSD, CPTSD, and matched HCs and clinical scale data from participants, the amplitude of Low Fluctuations (ALFF) and functional connectivity in different brain regions were analyzed, and correlations between neuroimaging features and clinical indicators were examined.

    The study found that patients with CPTSD exhibited increased ALFF in the left prefrontal cortex, right supplementary motor area (SMA), and right superior parietal lobule, while showing decreased ALFF in the left calcarine sulcus and right temporal lobe. Patients with PTSD demonstrated increased ALFF in the left insula and decreased ALFF in the left angular gyrus, which was negatively correlated with negative alterations in cognition and mood. Both disorders showed decreased ALFF in several prefrontal regions. Additionally, PTSD exhibited enhanced connectivity between the right SMA and right precuneus, while both disorders showed increased functional connectivity between the caudate nucleus and lingual gyrus.

    This study suggests distinct neurobiological patterns between PTSD and CPTSD, which may be associated with between-group differences in trauma timing categories. These findings offer preliminary insights and testable hypotheses regarding neurobiological differences between PTSD and CPTSD, and may serve as a preliminary reference for future investigations aimed at identifying neural markers to distinguish between the two conditions.

    Not applicable.
    Mental Health
    Care/Management
  • Alterations of microRNAs across human and mouse limbic brain areas: molecular mechanisms and biological processes involved in major depressive disorder.
    5 days ago
    The etiology of major depressive disorder (MDD) is multifactorial with both genetic and environmental factors, such as adverse/stressful life events, contributing to risk. There is some evidence suggesting that microRNAs (miRNAs) mediate environmental-genetic interaction leading to the brain dysfunctions that underlie MDD. However, changes in miRNAs expression in human brain regions due to stress and associated with MDD are unclear. To increase the evidence in this regard, miRNA sequencing was performed on tissue samples of subgenual anterior cingulate cortex (sgACC) obtained from depressed patients and control subjects, as well on tissue samples of medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) from mice exposed to chronic social stress (CSS) and control animals. DESeq2 was applied to identify differentially expressed miRNAs (DEMs) and weighted co-expression network preservation analysis to uncover conserved molecular mechanisms between species. Finally, pathways obtained from DESeq2 and preservation analyses were overlapped to robustly identify MDD-related processes across bioinformatic approaches.Eighteen DEMs were identified in the human sgACC, 11 in the mPFC and 9 in the BLA of mice. The human sgACC DEMs were involved mainly in intracellular signaling and immune system-related pathways. The mouse mPFC and BLA DEMs were mainly involved in, respectively, intracellular signaling and nervous system functions. Preservation patterns between humans and mice indicated an over-representation of processes related to cellular signaling. Transcriptional regulation by MECP2 and Protein Kinase A signaling were the two pathways consistently altered across species, brain regions, and bioinformatic approaches. Although further studies are needed, they could represent a novel target for intervention strategies and confirm the dysregulation of intracellular signaling, immune, neuronal and synaptic functions in MDD.
    Mental Health
    Policy
  • DNA-Protective Effects of Crocus sativus Stamen Extracts and Their Safety Assessment for Use as Natural Bioactive Agents.
    5 days ago
    The stamens of Crocus sativus L., often discarded as floral waste, are rich in flavonoids and phenolics. This study investigated their toxicological safety, antigenotoxic potential, and molecular mechanisms of protection against cyclophosphamide (CP)-induced genotoxicity. Hydroethanolic and hydromethanolic extracts were prepared, and acute oral toxicity was assessed in mice following the Organization for Economic Co-operation and Development guideline 423. Genotoxicity and its amelioration were evaluated in rat and mouse leukocytes by employing the alkaline comet assay. Oxidative stress markers, including superoxide dismutase activity, as well as malondialdehyde and glutathione levels, in hepatic and renal tissues were quantified. In parallel, nine major metabolites were identified in the extracts and were molecularly docked with key enzymes involved in CP bioactivation (CYP2B6), aldehyde detoxification (ALDH1A1), DNA repair (OGG1), and oxidative stress regulation (Keap1-Kelch domain; Protein Data Bank ID: 7K2A). The extracts were non-toxic up to 4,000 mg/kg and did not exhibit any genotoxicity. Pre-treatment with extracts (200 mg/kg body weight) significantly attenuated CP-induced DNA damage and restored antioxidant enzyme levels. Docking results supported these observations: rutin demonstrated a high affinity for CYP2B6 (-11.2 kcal/mol) and favorable binding to 7K2A (-9.7 kcal/mol); catechin gallate bound tightly to ALDH1A1 (-10.0 kcal/mol) and OGG1 (-9.2 kcal/mol). These findings suggest reduced CP activation, but enhanced detoxification and DNA repair. In conclusion, the extracts of C. sativus stamens are safe and possess robust antioxidant and antigenotoxic properties, confirmed by molecular docking. These findings highlight their potential as natural protective agents against chemotherapy-induced genotoxicity.
    Mental Health
    Policy
  • Virtual reality-induced emotion recognition with deep learning-based multimodal physiological feature fusion.
    5 days ago
    Recognizing emotions objectively and accurately remains challenging because of the limited ecological validity, informational incompleteness, and constrained model performance of conventional approaches. This study addresses these limitations holistically by investigating a novel framework that integrates ecologically valid virtual reality (VR) for emotion elicitation with deep learning-based multimodal physiological signal fusion.

    An immersive VR environment was developed to effectively elicit three target emotional states: positive, neutral, and negative. Synchronized physiological signals-electroencephalography (EEG), electrocardiography (ECG), and galvanic skin response (GSR)-were recorded from 20 healthy participants alongside subjective self-assessment data. After preprocessing and feature extraction, a nested cross-validation procedure was employed to prevent data leakage: within each of the five folds, feature selection (one-way repeated-measures ANOVA, α = 0.05) was performed solely on the training data. A hybrid network architecture combining principal component analysis (PCA) with long short-term memory (LSTM) was employed for dimensionality reduction and modeling. The PCA retained components explaining 90% cumulative variance, while the LSTM layer contained 96 hidden units, followed by three fully connected layers with integrated dropout regularization. Model performance was evaluated using this rigorous cross-validation framework and compared against baseline models including support vector machine (SVM), random forest (RF), k-nearest neighbors (k-NN), and extreme gradient boosting (XGBoost).

    Subjective evaluation results confirmed the effectiveness of VR-induced emotion elicitation. At the group level, one-way repeated-measures analysis of variance revealed significant main effects of emotional states (p < 0.05) on multiple physiological features: EEG frontal alpha asymmetry indices (AI_F4/F3, AI_F8/F7), ECG indices (SDNN, RMSSD, LF/HF ratio, sample entropy), and GSR measures (SCL, NS.SCRs). Employing a nested cross-validation framework to prevent data leakage, the PCA-LSTM model achieved a mean accuracy of 87.18% ± 2.28% under five-fold cross-validation, significantly outperforming SVM (75.83% ± 4.25%), RF (78.89% ± 6.85%), k-NN (72.78% ± 5.21%), and XGBoost (81.67% ± 5.83%).

    This study validates that integrating an ecologically valid VR emotion elicitation paradigm with a multimodal PCA-LSTM fusion model effectively enhances the objectivity and accuracy of emotion recognition. The proposed framework provides an effective solution to overcome the bottlenecks of ecological validity and quantification precision in traditional methods, demonstrating preliminary application potential in intelligent human-computer interaction and mental-health monitoring domains.
    Mental Health
    Policy
  • Case Report: Overload of a cross-country skier in elite sports, somatoform autonomic disorder, and end-of-career support.
    5 days ago
    In recent years, sports psychiatry and psychotherapy has developed rapidly. Under the umbrella of the International Society for Sports Psychiatry (ISSP), the first international consensus statement on sports psychiatry was recently published. Fields of sports psychiatry were identified. In the field of competitive and elite sports, the end of a sports career is a vulnerable phase. The end of a sports career can lead to an increased prevalence of psychiatric symptoms and disorders. This is illustrated using the case of a cross-country skier.

    The interactions between success, mental health, stress, training and overload are presented. In this context, a treatment with the Synergetic Navigation System (SNS) for digitized real-time monitoring is presented, considering the interaction of the various factors. Symptoms of overtraining were apparently helpful in treating somatoform autonomic dysfunction. The pre-treatment proved helpful when the athlete returned for treatment years later due to depression at the end of his career.

    To set a standard of service and a direction for future development in the field of sports psychiatry and psychotherapy, it is necessary to define typical and problematic issues to develop common approaches. The end of a career is an important issue in competitive and elite sports, and one in which athletes need support, recommended with integration into mental health care and prevention concepts.

    At the end of a sports career thorough and comprehensive preparation for post sport life is highly recommended. An "Exit Health Examination" including mental health exploration and "After Career Consultations" could be beneficial.
    Mental Health
    Advocacy
  • Individual and combined associations of modifiable metabolic health and lifestyle with low back pain, neck pain, and functional limitation: evidence from a nationally cross-sectional study.
    5 days ago
    Although healthy lifestyles are prioritized for the self-management of chronic low back pain (LBP) and neck pain (NP), the individual and combined associations of metabolic health and lifestyle with LBP, NP, and related functional limitations remain unclear. This study aimed to evaluate these associations and support risk stratification across different metabolic and lifestyle profiles.

    This cross-sectional study used data from the US National Health and Nutrition Examination Survey (1999-2018) to analyze two cohorts: pain cohort (n = 10286) and functional limitation cohort (n = 28513). Metabolic factors included abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. Lifestyle factors included smoking, alcohol consumption, diet, and physical activity. Outcomes, including LBP, NP, and back- or neck-related functional limitation (BN-FL), were assessed by self-reported questionnaires. Associations between risk factors and outcomes were assessed using multivariable logistic regression.

    Individuals with poor metabolic-lifestyle status had the highest prevalence of LBP (42.6%), NP (21.4%), and BN-FL (17.6%). Physical inactivity showed the largest estimated population-attributable fraction (PAF) for LBP and NP (20.8% and 20.5%, respectively), while abdominal obesity (15.1%) and smoking (14.0%) showed the largest estimated PAFs for BN-FL. Poor metabolic status was associated with higher odds of LBP (OR = 1.470, 95% CI: 1.227-1.760) and BN-FL (OR = 2.404, 95% CI: 1.977-2.923), while poor lifestyle was associated with higher odds across all outcomes. Worsening lifestyle status was consistently associated with higher odds of LBP across all metabolic strata. The combination of poor metabolic-lifestyle status was associated with the highest odds of LBP (OR = 3.435, 95% CI: 2.026-5.824) and BN-FL (OR = 4.378, 95% CI: 2.347-8.167).

    Both metabolic health and lifestyles were associated with LBP and BN-FL, while only lifestyles were linked to NP. Combined unfavorable metabolic and lifestyle profiles were associated with higher odds of LBP and BN-FL, underscoring the importance of both metabolic and lifestyle modification.
    Non-Communicable Diseases
    Care/Management
  • An Ionic Liquid-Based Enteric Formulation for Enhanced Oral Delivery of Semaglutide in Type 2 Diabetes Mellitus.
    5 days ago
    Oral delivery of peptide therapeutics remains challenging due to gastrointestinal degradation, poor epithelial permeability, and extremely low bioavailability. To address these limitations, we developed an enteric solid formulation based on sorbic acid-choline ionic liquids (ILs) for the oral delivery of semaglutide (Sema), a glucagon-like peptide-1 (GLP-1) analogue. The IL-based enteric system was designed to enhance peptide stability, reduce gastric degradation, and promote intestinal absorption. In vitro studies demonstrated strong resistance to acidic conditions and pH-responsive release in simulated intestinal fluid. In vivo imaging further revealed prolonged intestinal retention of the IL-loaded enteric particles. Pharmacokinetic evaluation showed a 2.3-fold increase in maximum plasma concentration compared to the reference Rybelsus. In type 2 diabetes mellitus (T2DM) mice, the formulation achieved glucose-lowering efficacy comparable to subcutaneous Sema administration, with additional improvements in hepatic histology. Importantly, repeated-dose studies indicated favorable systemic and gastrointestinal tolerability under the tested conditions. Collectively, these results demonstrate that IL-based enteric formulation enhances oral peptide exposure while maintaining safety, offering a promising strategy for noninvasive T2DM management.
    Diabetes
    Diabetes type 2
    Access
  • Evaluating iPSC-based interventions for diabetes: a systematic review and meta-analysis.
    5 days ago
    Diabetes mellitus (DM) is characterized by progressive β-cell dysfunction, and current therapies improve glycemic control without restoring endogenous β-cell mass. Induced pluripotent stem cell (iPSC)-based approaches offer a potential regenerative strategy. This systematic review and meta-analysis evaluates the efficacy and safety of iPSC-based interventions for diabetes in preclinical models.

    A comprehensive literature search was conducted in PubMed, ScienceDirect, and Web of Science for studies published up to November 2025. Studies assessing iPSC-based therapies in diabetic models were systematically reviewed and quantitatively synthesized.

    Thirty-one preclinical studies involving 424 animals were included. iPSC-based interventions were associated with reduced mortality (odds ratio [OR] 0.14) and reductions in blood glucose across 21 studies (mean difference [MD]  -267.36). Glucose-lowering effects were observed under fasting, non-fasting, and glucose-challenge conditions and were accompanied by increased insulin and C-peptide levels. Improvements were also reported in several diabetes-related complications, including cardiac dysfunction, impaired wound healing, neuropathy, and retinopathy.

    iPSC-based therapies show potential to improve glycemic control and diabetes-related complications in preclinical models, likely through a combination of endocrine replacement and paracrine-mediated regenerative mechanisms. However, substantial heterogeneity across outcome assessments, reliance on short- to mid-term follow-up, and limitations of experimental disease models constrain the interpretation and generalizability of these findings. Immune compatibility, long-term safety, and scalable manufacturing remain key challenges for clinical translation.
    Diabetes
    Care/Management
  • Association between self-purchased medication use and gastric disease among Chinese adults: a cross-sectional analysis based on CHARLS 2018 data.
    5 days ago
    Gastric diseases are a major health burden, especially in East Asia, with high incidence and mortality rates. While Helicobacter pylori infection and poor lifestyle behaviors are established risk factors, the impact of drug-related gastric injury in aging populations remains underexplored. In China, polypharmacy is common among older adults, with nearly 40% using self-purchased medications without professional guidance. Similar trends are observed in other aging societies, highlighting the global challenge of unregulated drug use. Existing studies lack adjustments for comorbidities, prediction tools, and methodological innovation. This study analyzes CHARLS 2018 data to: (1) examine the relationship between self-purchased medication use and gastric disease, and (2) identified strongly associated groups, such as patients with chronic kidney disease (CKD) and diabetes.

    We included 19,752 participants from the CHARLS database. Participants were divided into gastric disease and control groups based on DA007_10 questionnaires. We compared baseline characteristics, including self-purchased medication use, between groups. Multivariate logistic regression models were used to assess the correlation between self-purchased medication use and gastric disease. The receiver operating characteristic (ROC) curve evaluated Model 3's predictive performance. Stratified analysis was conducted to assess the stability of the results.

    Significant differences were observed between the gastric disease (n = 659) and control (n = 5,428) groups in factors such as ethnicity, self-reported health status, hypertension, dyslipidemia, diabetes, chronic lung diseases, liver disease, kidney disease, smoking history, and medication use. In all models, self-purchasing medication was associated with an increased prevalence of gastric disease (adjusted OR = 1.75, 95% CI 1.46-2.09, p < 0.001), including Model 3 (adjusted OR = 1.75, 95% CI 1.46-2.09, p < 0.001). The model demonstrated moderate discriminatory ability in distinguishing individuals with and without gastric disease (AUC = 0.71). Stratified analyses revealed that the association between self-purchased medication use and gastric disease risk was consistent across covariates, with stronger effects observed in participants with CKD (adjusted OR = 1.89) and diabetes (OR = 1.82).

    This study found that self-purchasing medication was positively correlated with the risk of gastric disease in Chinese older adults (adjusted OR = 1.75), and the association was stronger among those with chronic kidney disease (adjusted OR = 1.89) or diabetes (OR = 1.82). This finding provides a reference for the risk stratification and prevention strategies of gastric disease.
    Diabetes
    Care/Management