Depression is a highly recurrent psychiatric disorder characterized by persistent low mood, anhedonia, and sleep disturbances. The clinical diagnosis of depression currently relies primarily on clinical interviews and standardized assessment scales, lacking objective biological markers. This increases the risk of misdiagnosis and missed diagnosis, while also limiting the precise differentiation of disease subtypes and the individualized prediction of treatment response. Identifying reliable biomarkers has therefore become a major research focus. This study, based on bioinformatics analysis of the GEO database, found that fibroblast growth factor 13 (FGF13) was significantly reduced in the serum of patients with major depressive disorder (MDD). FGF13 belongs to the fibroblast homologous factor (FHF) family and is enriched in neurons of the brain, where it regulates neuronal excitability and synaptic plasticity. However, the role of FGF13 in depression remains unclear. Based on the results of the bioinformatics analysis, experimental validation demonstrated that Fgf13 expression was significantly reduced in corticosterone (CORT)-induced PC12 and SH-SY5Y cells, as well as in the hippocampus of chronic unpredictable mild stress (CUMS) rats, as shown by qRT-PCR and Western blot analyses. Functional experiments demonstrated that FGF13 overexpression enhanced the expression of synaptic plasticity-related proteins (Syn, PSD95, BDNF) and anti-apoptotic protein (Bcl-2), while suppressing pro-apoptotic proteins (Bax, Cleaved-caspase-3) and activating the PI3K/AKT pathway. These effects were markedly reversed by treatment with the PI3K inhibitor LY294002. Furthermore, FGF13 overexpression improved neuronal apoptosis and morphological damage in the hippocampus of CUMS rats. Serum ELISA analysis revealed significantly reduced FGF13 levels in patients with depression. Logistic regression analysis showed a negative association between FGF13 expression and depression risk, while ROC analysis demonstrated good diagnostic performance (AUC = 0.936). Collectively, these findings suggest that FGF13 participates in the pathogenesis of depression by regulating synaptic plasticity and neuronal apoptosis and may serve as a promising biomarker and potential therapeutic target.

BACKGROUND: Black transgender women are disproportionately exposed to discrimination and healthcare barriers associated with poor health and delayed treatment-seeking. Consequently, traditional treatment pathways may not be accessible. Thus, health self-management (HSM) may be critical in promoting health among Black transgender women. PURPOSE: The purpose of this study is to examine the relationships among intersectional discrimination, self-efficacy for health management, and mental health outcomes (PTSD symptoms, depressive symptoms, and unhealthy days) among Black transgender women, and to determine whether self-efficacy modifies or explains the association between intersectional discrimination and these health outcomes. METHODS: We analyzed quantitative survey data from a community-based United States sample of 154 Black transgender women to advance our understanding of the associations between intersectional discrimination, self-efficacy to manage one's health, and distal health outcomes. Analyses included Pearson's correlations, T-tests, and multiple linear regression. RESULTS: Higher self-efficacy was associated with better mental health overall but did not consistently buffer the effects of intersectional discrimination, suggesting partial mediation rather than full mediation or moderation. DISCUSSION: Among Black transgender women, racism and cisgenderism may be influencing other components in the pathway between context and health outcomes, contributing to higher self-reported self-efficacy or reducing the potential effect of self-efficacy on health outcomes. CONCLUSION: Future research should further examine the historical and present-day prejudicial systems that affect one's self-efficacy to manage their health and take an anti-cisgenderist and anti-racist approach to discussing HSM with Black transgender women.

INTRODUCTION: Anxiety is a common mental disorder with high individual and public health costs. Psychometric scales are frequently applied to describe anxiety severity; however, their subjective nature reduces measurement precision. Heart rate variability (HRV) may serve as a complementary tool for assessing anxiety by adding physiological information beyond subjective symptom ratings. METHODS: We conducted a systematic review and meta-analysis, reported in accordance with PRISMA 2020 (PROSPERO: CRD42024623381). We considered studies on adult populations who had been given validated anxiety scales (BAI, HAM-A and STAI) as well as quantitative HRV parameters (HF, LF, LF/HF, RMSSD, and SDNN). Correlation coefficients quantifying the associations for multiple psychometric scale - HRV parameter pairs were synthesised employing an inverse-variance random- effects meta-analysis framework. RESULTS: A total of 79 studies were included, of which 39 were eligible in a quantitative analysis. Three statistically significant associations were identified: (1) BAI and HF showed a weak negative correlation (r = -0.09, p = .0239), (2) HAM-A and HF had a moderate negative correlation (r = -0.32, p = .0423), while (3) STAI and LF/HF ratio showed a positive correlation (r = 0.39, p = .0017). Other parameters did not show significant associations. CONCLUSION: Selected HRV parameters showed associations with anxiety severity, especially HF with BAI and HAM-A, and LF/HF with STAI. While HRV is not a replacement for psychometric scales, it may contribute as a complementary tool for characterising autonomic regulation associated with anxiety severity.

BACKGROUND: Owing to medical advances and improved living conditions, life expectancy continues to increase. Consequently, population aging poses growing challenges for healthcare systems. OBJECTIVES: The aim of this study was to assess whether men's perceptions of aging have changed between 2013 and 2023. MATERIAL AND METHODS: A cross-sectional comparative study was conducted in 2013 and 2023 using identical research tools and inclusion criteria. Participants were randomly selected from hospitalized patients in the Podlaskie Province, Poland. The following instruments were used: an original questionnaire, the Satisfaction with Life Scale (SWLS), the Generalised Self-Efficacy Scale (GSES), the Beck Depression Inventory (BDI), the Inventory of Health Behaviour (IHB), the Androgen Deficiency in Aging Male questionnaire (ADAM), and the Aging Males' Symptoms Scale (AMS). RESULTS: Most respondents in both 2013 and 2023 associated old age with declining testosterone levels and considered it to begin after the age of 75. Men generally rated their health as good and regarded andropause as a natural process. Psychological symptoms of aging were reported by 80.5% of respondents in 2013 and 75.9% in 2023, while sexual dysfunction was reported by 65.8% and 63.3%, respectively. More than half of the respondents had no depressive symptoms according to the BDI. Men with high self-efficacy predominated in both study periods. CONCLUSIONS: Respondents' knowledge of the aging process remains incomplete and often inaccurate. Despite this, men generally rated their health positively and perceived andropause as a natural process. Psychological symptoms of aging and sexual dysfunction were reported by a substantial proportion of participants.

People with substance use disorders (PWSUDs) frequently experience multifaceted challenges, including depression, stigma, and social instability, which can negatively affect their quality of life (QoL). The present study explored the potential predictors of QoL among PWSUDs. The sample consisted of 300 PWSUDs (85% males; mean [SD] age = 44.73 [10.01] years), comprising equal groups of PWSUDs with amphetamine, opioid, and alcohol concerns. Variables such as education, employment, depression, self-esteem, and stigma were assessed. The Taiwan version of the World Health Organization Quality of Life (WHOQOL) Questionnaire was adapted to assess QoL. Hierarchical regression analyses were conducted to examine associations with QoL across four domains. A multiple mediator modeling approach was used to assess whether self-stigma and depression mediated the relationship between perceived stigma and QoL. Higher depression scores were consistently associated with lower QoL across all domains. Education and employment were positively associated with physical QoL. In the psychological domain, both lower depression and higher self-stigma were associated with higher QoL. Perceived stigma was negatively associated with social QoL, and lower education predicted poorer environmental QoL. Mediation analyses suggested that depression played a stronger mediating role than self-stigma in the association between perceived stigma and QoL. Depression and stigma significantly related to QoL among PWSUDs. Mediational pathways suggest that targeting depression may mediate the negative association between stigma and QoL. Interventions addressing both affective and social dimensions may help promote recovery.

Acculturative stress, arising from cultural and psychological changes following intercultural contact, may increase vulnerability to maladaptive coping behaviors, including emotional eating. Evidence suggests that the association between acculturative stress and disordered eating differs by sex; however, Arab migrant populations remain underrepresented in this field. This study aimed to examine sex-stratified, migration-related predictors of emotional eating among Arab migrants living in Türkiye. This cross-sectional research was conducted between June 2022 and March 2024 and included 528 adults who migrated to Türkiye from Arab countries. Sociodemographic and migration-related characteristics were collected. Acculturative stress was assessed using the Acculturative Stress-Social, Attitudinal, Familial, and Environmental-Revised Short Form (SAFE-Short), and emotional eating was evaluated with Emotional Eating Scale (EES). Body mass index (BMI) was calculated from self-reported weight and height. Sex-stratified regression analyses were performed. BMI was positively associated with all EES subscales in both female and male participants. However, among male participants, the overall regression models for the Anger and Anxiety subdimensions were not statistically significant. Also, no sociodemographic or migration-related variables were associated with emotional eating among male participants. In females, higher age was associated with lower depression-related emotional eating, while single marital status was associated with higher anger-related emotional eating. Employment was associated with lower anger- and anxiety-related emotional eating. Migration due to personal safety concerns, living with individuals from different countries, and higher acculturative stress were associated with higher emotional eating scores in females. These findings may indicate that in social contexts where direct emotional expression is less acceptable for females, emotions are more likely to be regulated through eating-related behaviors.

Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a recently defined malformation of cortical development that is an important cause of childhood-onset drug-resistant epilepsy. Clinically, the epilepsies associated with MOGHE are heterogeneous, with infantile epileptic spasms syndrome (IESS) being the most common manifestation. Histopathologically, MOGHE demonstrates subtle cortical dyslamination, heterotopic neurons in the white matter, hypomyelination, and a distinctive increase in the density and clustering of oligodendroglial cells, features that distinguish it from other malformations of cortical development such as focal cortical dysplasia (FCD). Recent genetic analyses of epileptogenic tissue resected from individuals with MOGHE have identified somatic mosaic loss-of-function variants in SLC35A2. This gene encodes the Golgi transmembrane UDP-galactose transporter, suggesting disrupted N-glycosylation as a distinct pathogenic mechanism underlying epilepsy in this disorder. In this review, we present the current clinical, histopathological, and molecular understanding of MOGHE, with a particular focus on recent insights gained from experimental rodent and human cellular models of SLC35A2 deficiency. We contextualise these findings against established models of mTORopathies including FCD type 2, placing MOGHE within the broader malformation of cortical development spectrum. Synthesising this evidence, we observe that neuronal activity in models of both MOGHE and mTORopathies such as FCD type 2 converge on reduced action potential firing, despite their distinct genetic aetiologies. Finally, we discuss how these findings inform our understanding of epileptogenesis, especially the emergence of infantile epileptic spasms, and the development of future precision therapeutic strategies across malformations of cortical development.

BACKGROUND: Termination for medical reasons (TFMR) is an essential aspect of reproductive healthcare. While physical and emotional care of the birthing parent is central within healthcare systems, less is known about the experiences and support needs of non-birthing partners during this process. OBJECTIVE: To explore fathers' and non-birthing partners' perceptions and experiences of support (covering clinical, psychological, and social support) during a TFMR. DESIGN: A qualitative study using semi-structured interviews. SETTING AND PARTICIPANTS: Ten fathers/non-birthing partners who had experienced TFMR in the last 7 years, identified via social media or snowball sampling, were interviewed. ANALYSIS: Data were analysed using inductive thematic analysis and a mixture of semantic and latent coding of the data. RESULTS: An overarching theme of Support in the shadows was identified, capturing how non-birthing partners were consistently present but rarely the focus of explicit or sustained care or support. Three themes were developed under the main theme of support in the shadows: (a) Feeling invisible, (b) seeking whole-person support and (c) partners as a support rather than being supported. DISCUSSION: In common with other forms of pregnancy loss, fathers/non-birthing partners described a pattern of silent responsibility, emotional invisibility and a lack of meaningful recognition of their needs. When care was individualised and specific to non-birthing partners, it was experienced as supportive. CONCLUSIONS: The support that fathers/non-birthing partners experienced during TFMR was largely incidental rather than embedded. Partners desired care and support that was deliberate, inclusive and individualised and covered clinical, psychological and social aspects. PATIENT OR PUBLIC CONTRIBUTION: A parent with lived experience of TFMR was involved in the study conception and methodology. The lived experience parent advised on study design and the presentation of participant information. Parents who had lived experience of TFMR in the last 7 years were interviewed for the study as participants.

INTRODUCTION: Medial opening wedge high tibial osteotomy (MOWHTO) and unicompartmental knee arthroplasty (UKA) are established treatments for knee osteoarthritis (KOA). This study compared their effects on mental health outcomes. METHODS: A retrospective cohort study was conducted on patients who underwent MOWHTO or UKA between 2019 and 2023 at a single tertiary institution. The primary outcome measure, the Short Form-36 mental component score (SF-36 MCS), was recorded at baseline, six months and two years post-procedure. Secondary outcomes included the SF-36 physical component score (PCS) and the Oxford knee score (OKS). A total of 105 MOWHTO and 89 UKA procedures were performed. Propensity score matching accounted for preoperative scores, age, gender and body mass index, yielding 51 patients per group. Multivariable regression was used to examine associations between preoperative MCS and postoperative outcomes. Baseline predictors of postoperative MCS were analysed. The level of significance was set at P < 0.05. RESULTS: At six months postoperatively, the UKA group demonstrated better PCS (MOWHTO 42.0 vs UKA 49.6, P < 0.001) and OKS (MOWHTO 23.0 vs UKA 18.8, P = 0.002). At two years, both groups achieved similar improvements in SF-36 MCS, SF-36 PCS and OKS. Preoperative MCS showed a moderate association with postoperative MCS and weak associations with postoperative PCS and OKS. Preoperative MCS was the only baseline factor independently associated with postoperative MCS. CONCLUSION: In patients with KOA, MOWHTO and UKA achieved similar improvements in mental health scores at two years. Preoperative mental health is an important determinant of postoperative mental health, highlighting its importance in preoperative assessment and counselling.

Introduction The use of health services expanded during the pandemic and became a regular part of healthcare. There is not a lot of information about how these services are used over the long term and how patients engage with them. This study examined how patients used telemental health services at King Abdulaziz Medical City (KAMC), Riyadh, Kingdom of Saudi Arabia, from 2019 to 2025. Objectives To evaluate how telemental health services were used and how patients engaged with them during the time before the pandemic, during the pandemic, and after the pandemic. The study also compared how many appointments were completed and the characteristics of patients who had virtual appointments versus in-person appointments. Methods This was a retrospective, repeated cross-sectional census study of electronic health record data on all scheduled mental health appointments, virtual and in-person, at KAMC from January 1, 2019, to December 31, 2025. All eligible encounters and unique patients across 12 facilities were included using total enumeration rather than sampling. Data were cleaned and analyzed in Python using Google Colab. Descriptive statistics were used to summarize appointment and patient characteristics. Chi-square tests were used to compare categorical variables, including appointment completion by encounter type, and the Mann-Whitney U test was used to compare patient age between virtual and in-person appointments. A binary logistic regression model was used to identify factors associated with appointment completion, including encounter type, pandemic period, and patient demographics. Results The study included 479,643 appointments with 51,323 patients at 12 facilities. Overall, 9% of the appointments were virtual. In 2019, there were no appointments, but their use increased during the pandemic and then stayed steady at around 11% to 12% per year after 2021. Overall, 55% of appointments were completed. Virtual appointments had a higher completion rate than in-person appointments, with 60% of virtual appointments being completed compared to 54% of in-person appointments. We also found that patients who had virtual appointments were substantially older and that virtual appointments were mostly used for follow-up visits rather than new patient appointments.  Conclusion Telemental health services went from being an emergency solution during the pandemic to a part of mental health services at the facility. The study found that virtual appointments were associated with patient engagement, which means that patients were more likely to complete their appointments. These findings support the continued use of a hybrid of in-person and virtual mental health services. The findings provide information to support the planning and development of telemental health services. Telemental health services are a part of the healthcare system, and they can be an effective way to deliver the services.

BACKGROUND: Older adults with atrial fibrillation (AF)-associated acute ischemic stroke are prone to disability, depressive symptoms, and falls; the prognostic value of vitamin D status is uncertain. METHODS: We conducted a single-center prospective cohort study of patients aged ≥65 years with ECG-confirmed AF and imaging-confirmed acute ischemic stroke at a tertiary hospital in China (January 2022-August 2024). Serum 25-hydroxyvitamin D [25(OH)D] within 48 hours was modeled per 10 ng/mL decrement and as <20 vs ≥20 ng/mL. Outcomes were 3-month modified Rankin Scale (mRS) shift, Barthel Index (BI), and PHQ-9 ≥10, plus 12-month time to first fall (death as a competing event) and total falls rate. Models adjusted for prespecified baseline confounders. RESULTS: Among 802 participants, median age was 76.2 years (IQR, 71.6-80.6); 60.7% had 25(OH)D <20 ng/mL. Three-month mRS/BI, 3-month PHQ-9, and falls follow-up data were available for 776 (96.8%), 762 (95.0%), and 742 (92.5%) participants, respectively. Each 10 ng/mL lower 25(OH)D was associated with worse 3-month mRS shift (common OR 1.17, 95% CI 1.05-1.31) and lower BI (β -3.9, 95% CI -6.2 to -1.6). Depressive symptoms occurred in 16.8% and were more common with 25(OH)D <20 ng/mL (OR 1.54, 95% CI 1.07-2.22). Among 742 with falls follow-up, low 25(OH)D predicted first fall (HR 1.29, 95% CI 1.07-1.55) and a higher recurrent falls rate (IRR 1.33, 95% CI 1.10-1.61). CONCLUSION: Lower baseline 25(OH)D was consistently associated with poorer functional recovery, greater depressive symptom burden, and higher fall risk and recurrence, supporting 25(OH)D as a pragmatic prognostic marker; multicenter validation and targeted trials are warranted.

Giant cell arteritis (GCA) is the most common type of systemic vasculitis and predominantly affects women over the age of 50 years. Clinical presentation includes cranial and ocular involvement, joint and systemic features. Diagnosis is confirmed by positive temporal artery biopsy or ultrasound or large vessel vasculitis on positron emission tomography. Treatment includes high-dose glucocorticoids (GC) and immunosuppressants. Health-related quality of life (HRQoL) can be impacted by pain, fatigue, and sight loss; glucocorticoid therapy adds further physical, psychological, and social burdens. Patient-reported outcome measures (PROMs) aim to capture the impact of disease from the patient's perspective. A range of PROMs have been used to highlight the impact of GCA. The generic 36-Item Short Form Health Survey (SF-36) has demonstrated the effectiveness of novel treatments including Tocilizumab in clinical trials, the symptom-specific Hospital Anxiety and Depression scale has demonstrated 50% of people with GCA suffer with anxiety and a third depression, and condition-specific (GCA PRO) and treatment-specific (Steroid PRO) PROMs have been developed and validated in people with GCA for clinical practice and trials. Shared decision-making (SDM) is essential in GCA management, ensuring patients understand treatment options and decisions reflect their preferences and "what matters to them." PROMs support SDM and enhance the patient-clinician dialogue. Early evidence from use of the GCAPRO demonstrated that PROMs have helped patients explain their symptoms, providing clinicians with clearer insights into the patient's health. There is a growing role for electronic PROMs (E-PROMs) to support patient and clinician communication and facilitate effective clinical triage. Considerations about E-PROMs include potential for digital exclusion in older patients, data governance with online apps, and clinical safety (i.e., for people reporting active disease). To fully implement E-PROMS in clinical practice and gain the maximum benefit, full integration into intuitive clinical and patient systems will be required.

BACKGROUND: Recent evidence suggests that low-dose methotrexate might have antipsychotic properties. However, it remains unknown whether low-dose methotrexate is associated with a reduced risk of incident recorded psychosis in real-world data, whether these associations extend to other putatively immune-related common psychiatric conditions, or whether similar associations are observed with other disease-modifying anti-rheumatic drugs (DMARDs). METHODS: In this retrospective cohort study using electronic health records (TriNetX US Collaborative Network), we identified adults with rheumatoid arthritis (age ≤45 years at treatment initiation; data extracted from 1 January 2000 to 21 December 2025). The 5-year risk of an incident recorded psychosis (primary outcome) and bipolar, depression, or anxiety disorders (secondary outcomes) were compared between low-dose methotrexate and each of 14 comparator drugs used in rheumatoid arthritis - three primary comparators (non-steroidal anti-inflammatory drugs; NSAIDs, naproxen, diclofenac and celecoxib) and 11 secondary and exploratory DMARDs comparators. Cumulative incidences and ratios of restricted mean time lost (rRMTL) are reported. Results were Bonferroni-corrected for multiple comparison. FINDINGS: Comparator cohort sizes ranged from 1161 to 21,445 (mean ages 33.7-37.4 years). For the primary outcome of psychosis, initiation of low-dose methotrexate was associated with lower 5-year incidence of newly recorded psychosis than initiation of naproxen (rRMTL 0.69, 95% CI 0.55-0.87) or diclofenac (rRMTL 0.71, 0.56-0.89); no significant difference was observed versus celecoxib or biologic DMARDs. For the secondary outcomes, low-dose methotrexate was similarly associated with lower 5-year incidence of newly recorded bipolar disorder, depression, and anxiety compared with non-selective NSAIDs naproxen and diclofenac, with the mood and anxiety associations extending to the selective cyclo-oxygenase-2 inhibitor celecoxib. INTERPRETATION: In a real-world rheumatoid arthritis cohort, initiation of low-dose methotrexate was associated with lower 5-year incidence of newly recorded psychosis, bipolar disorder, depression, and anxiety than initiation of non-selective NSAIDs. Given that extensive trials of broad anti-inflammatories have yielded limited psychiatric benefit, the differential profile of low-dose methotrexate is consistent with a mechanism beyond simple inflammation suppression. We hypothesise potentiation of regulatory T cell-mediated control of systemic inflammation and neuro-glial regulation. The active-comparator observational design cannot establish causation; these findings are hypothesis-generating and confirmatory inference will require interventional studies. FUNDING: UK Research and Innovation (UKRI) Medical Research Council [grant number UKRI4403] Mental Health Platform. The National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research.

INTRODUCTION: Dental aesthetics plays a key role in children's social perception and psychosocial development. However, evidence on smile perception in children remains limited, highlighting the need for valid and reliable assessment tools. This study aimed to perform the cross-cultural adaptation and psychometric validation of the Smile Perception Questionnaire for Children Aged 8-10 Years (SPQ 8-10) for use in Turkish children. METHODS: This observational methodological validity-reliability study included 300 healthy children aged 8-10 years who attended the Department of Pediatric Dentistry at Bursa Uludag University and met the predefined eligibility criteria. Eligible participants were healthy children aged 8-10 years whose parents provided informed consent; children with previous or ongoing orthodontic treatment, systemic diseases, or mental, physical, hearing, or visual impairments affecting communication or questionnaire completion were excluded. The SPQ (8-10) was translated into Turkish using forward-backward translation and expert review. Standardized perioral smile images were digitally generated to represent different dental conditions, and each participant evaluated one randomly assigned image using a five-point Likert scale. Exploratory factor analysis (principal axis factoring) and confirmatory factor analysis (DWLS estimation) were conducted to assess construct validity. Internal consistency (Cronbach's α, McDonald's ω) and test-retest reliability (ICC) were evaluated. RESULTS: Cronbach's α coefficient for the scale was 0.844, while McDonald's ω coefficient was 0.847. The analysis yielded ICC (3,1) = 0.803, 95% CI [0.628, 0.901], indicating that the scale had good temporal stability. CFI and TLI values above 0.95 and an SRMR value below 0.06 suggest a good fit. RMSEA value was at the threshold (0.084). CONCLUSION: The final 10-item Turkish version of the SPQ (8-10) demonstrates adequate psychometric properties in terms of factorial structure, internal consistency, and temporal stability.

Laboratory research suggests that the attenuation of defensive responses during threat exposure relies on the inhibition of subcortical defense circuits orchestrated by the prefrontal cortex. This process may be reflected by increased vagal efferent activity on the autonomic nervous system. Here, we tested whether cardiac vagal efferent activity, indicated by vagally-mediated heart rate variability (vmHRV), is associated with reduced defensive responses during in-vivo threat exposure and whether it may serve as a physiological index of multi-level exposure responding. Thirty-three women with excessive fear of spiders underwent standardized exposure, where they first approached a living tarantula (approach phase) and subsequently progressed through stages of increasingly direct interactions with the spider (threat imminence task). Indices of cardiac vagal activity (vmHRV) and overall cardiac autonomic arousal (heart rate) were measured alongside self-reported fear and avoidance behavior (distance to spider, performance in threat imminence task). During approach, self-reported fear increased until it reached a stable ceiling. Concurrent vmHRV leveled accordingly, with greater activity being related to lower fear and reduced avoidance during the subsequent threat imminence task. From the very first minute, cardiac vagal activity was associated with the participants' ability to physically engage with the fear cue during threat imminence task, irrespective of covariations in self-reported fear. Our results suggest that cardiac vagal activity may represent inhibition of fear and avoidance during exposure to perceived threat. Cardiac vagal activity, indexed by vmHRV, could therefore represent an index of within-session multi-level responding to exposure and a promising target for adjuncts to promote fear reduction.

BACKGROUND AND AIM: The increasing incidence of cancer and the fact that the family is an important factor in cancer care; attention to the positive mental health of cancer patients should be sought to provide solutions to improve the mental health of these caregivers. The present study aimed to investigate the effect of web-based education on positive mental health of family caregivers of breast cancer patients undergoing chemotherapy in educational and treatment centers of Zahedan University of Medical Sciences. MATERIALS AND METHODS: This study is a semi-experimental study. The statistical population of the study included all family members of breast cancer patients undergoing chemotherapy who referred to Imam Ali Hospital in Zahedan in 1402. The samples included 70 people who were randomly assigned to two groups: the intervention group and the control group. Caregivers in the intervention group received the necessary training and education for 20 days through a website prepared by the researcher. Data collection was carried out using the demographic information formula and the 9-question positive mental health questionnaire of Lockett before the intervention and 30 days after the intervention. The data were analyzed using descriptive and analytical tests using SPSS 27 statistical software and independent t-tests, paired t-tests, and chi-square tests. RESULTS: Before the intervention, there was no significant difference between the two groups in terms of positive mental health (p = 0.43). However, after web-based training, the results of the analysis of covariance (ANCOVA) with adjustment for pre-test scores showed that the positive mental health score in the intervention group was 19.02 ± 3.05, compared to 15.94 ± 2.61 in the control group (p = 0.0001). CONCLUSION: The findings of this study suggest that web-based educational programs can enhance the positive mental health of family caregivers of breast cancer patients undergoing chemotherapy. Accordingly, such interventions may be considered an effective supportive approach for family caregivers in oncology care settings.

Major depressive disorder (MDD) remains a critical global health burden, and a substantial proportion of patients exhibit insufficient responses to conventional monoaminergic antidepressants. Selective inhibition of the two-pore domain potassium channel TREK1 has emerged as a promising antidepressant strategy; however, the regulatory mechanisms controlling TREK1 trafficking-particularly its functional coupling with G protein-coupled receptors (GPCRs)-remain poorly understood. Here, we established a cell-based screening platform using a biomolecular luminescence complementation (BiLC) assay to monitor agonist-induced changes in membrane-associated TREK1. Using this platform, we identified a TREK1-5-hydroxytryptamine receptor 4 (HTR4) complex in vitro and in native hippocampal tissues using biomolecular fluorescence complementation (BiFC), co-immunoprecipitation (Co-IP), and proximity ligation assays (PLA). Live-cell imaging demonstrated that treatment with the HTR4 agonist mosapride induces redistribution/internalization of a plasma membrane-associated TREK1-HTR4 pool into intracellular compartments. Electrophysiological recordings further confirmed that mosapride reduces TREK1 channel activity in an HTR4-dependent manner. In vivo, oral administration of mosapride for five days ameliorated lipopolysaccharide (LPS)-induced depressive-like behaviors in mice and preserved markers associated with hippocampal neurogenesis. Notably, viral expression of the TREK1 C-terminal interaction domain (C1), which competitively disrupts the TREK1-HTR4 complex, attenuated the neurogenic and behavioral effects of mosapride, supporting a causal role of TREK1 regulation in mediating these antidepressant-like actions. Collectively, our findings reveal a previously unrecognized mechanism in which HTR4 dynamically regulates TREK1 trafficking and function, and they highlight GPCR-based modulation of TREK1 as a potential therapeutic strategy for depressive disorders.

UNLABELLED: Obesity is a chronic relapsing disease leading to weight-related health risks for disorders such as cardiovascular diseases, type 2 diabetes, osteoarthritis, and depression. Many studies focus on these weight-related health risks. However, research on current self-reported social impacts and health complaints is limited. This study aims to investigate self-reported social impact and health complaints, received care aiming at lifestyle change, and perceived effectiveness of this care, by children with obesity and their parents. Secondarily, differences concerning sex, age, obesity-severity and frequency of received care were studied. Questionnaires were collected from children and adolescents aged 0-18 years visiting Obesity Center CGG. Data were analyzed regarding their social impacts, health complaints, received care, and perceived care effectiveness (0-10 scale). Children were categorized into sex, age, BMI, and care categories. Descriptive statistics were performed using chi-square tests and post hoc analyses to examine differences between categories. 86.8% of the patients self-reported experiencing social impact and 92.3% reported health complaints. Most frequently reported social impacts were difficulty to find fitting clothes (70.1%), problems in mobility and sports (63.7%), and bullying (41.6%); most reported health complaints were abdominal pain (38.8%), headache (34.8%), and musculoskeletal pain (34.1%). The dietician (64.1%) was most frequently reported as received care, and effectiveness scores ranged between 0 and 4 out of 10. CONCLUSIONS:  A substantial percentage of patients experience social impacts and health complaints affecting their well-being and quality of life. Low perceived effectiveness of interventions calls for a more innovative and comprehensive care framework incorporating these children's needs. WHAT IS KNOWN: • Children with overweight and obesity face a wide range of adverse health consequences and social challenges. • However, the number and types of health issues experienced by children themselves and studying per range of age, BMI-stage or care trajectory have not been systematically investigated. WHAT IS NEW: • A high percentage of children experience social impacts (87%) and health complaints (70%) aff ecting their well-being and quality of life, and perceived eff ectiveness of lifestyle interventions is low. The main reported healthcomplaints abdominal pain, headache, musculoskeletal pain and snoring loudly were mostly observed in girls withobesity aged 12-18 years, who received three or more care types. • The study demonstrated that perceived treatment effectiveness by children and parents declined with increasingobesity severity.

BACKGROUND: Arthrofibrosis is a complication of total knee arthroplasty (TKA) and a common cause of aseptic revision TKA (rTKA). Since keloidosis and arthrofibrosis are both fibroproliferative disorders, we hypothesized that a history of keloids may predispose patients to developing arthrofibrosis post-TKA. The purpose of this study was to evaluate the impact of prior keloid formation on arthrofibrosis and rTKA incidence within one and two years post-TKA. METHODS: Patients who underwent TKA and had a history of keloids were identified using a national electronic health records database and propensity matched on a 1:1 basis by age, sex, race, ethnicity, Charlson Comorbidity Index (CCI), nicotine dependence, obesity, anxiety, and depression status. Exclusion criteria were post-traumatic osteoarthritis, lower-limb neoplasms, prior arthroscopies, osteotomies, or fractures. Primary outcomes were arthrofibrosis and rTKA occurring within one and two years post-TKA. A total of 1,205 patients were identified in each cohort after matching. RESULTS: Patients who had a history of keloids demonstrated a statistically significant increase in risk of arthrofibrosis at both one year (4.7 versus 2.2%; relative risk (RR) 2.11, 95% confidence interval (CI): 1.34 to 3.31) and two years (4.7 versus 2.4%; RR 1.97, 95% CI: 1.27 to 3.05) following TKA. Rates of revision TKA did not differ significantly two years after TKA (1.6 versus 1.1%; RR 1.45, 95% CI: 0.73 to 2.96). CONCLUSION: In this study utilizing a large national database, history of keloid formation was associated with significantly higher arthrofibrosis rates one and two years post-TKA compared to matched controls. This data is consistent with the sparse literature showing associations between keloidosis and other fibroproliferative disorders with arthrofibrosis. This information may help guide clinicians in their preoperative counseling and postoperative stiffness management.

The immune system plays a crucial role in defending the body against harmful invaders, with immunoglobulins being key players in pathogen recognition and neutralization. Immunoglobulin dysregulation is linked to various diseases, including autoimmune disorders, immunodeficiencies, and allergies. Previous studies suggest that depression can alter immune function by modifying immunoglobulin production, which may contribute to increased vulnerability to infections and autoimmune diseases. In this study, we examined the association between the immunoglobulin (Ig) subclasses IgA, IgG, IgM, and IgE and different types of depression, alongside epidemiological and environmental factors, using two independent samples from the population-based SHIP (Study of Health in Pomerania) project (TREND-0 N = 3750, START-2 N = 1958). Multiple linear regression analyses revealed that the environmental factors showed distinct associations with immunoglobulin levels. In TREND-0, lifetime depressive disorder was associated with decreased total IgA (p = 0.019) and increased total IgM (p = 0.026), indicating a shift toward impaired local immunity and heightened global immunity. Current depressive symptoms correlated with reduced IgG (p = 0.039) levels, reflecting impaired long-term immunity and immunological memory. These associations were specifically observed in depression, with no significant effects from broader psychiatric conditions. Results on current depression were replicated in START-2, a measurement of lifetime depression was not available here. Additionally, a history of childhood trauma was linked to elevated total IgE (p = 0.028), suggesting an increased susceptibility to allergic responses. These findings highlight the complex relationship between depression and immune function, emphasizing the need for further exploration of these associations in immune-related pathologies.

While cognitive and behavioral manifestations of obsessive-compulsive disorder (OCD) are well known, the neuronal dynamics underlying these symptoms remain poorly understood. Theoretical work suggests that changes in the attractor dynamics of neuronal networks towards increased stability and decreased flexibility might cause behavioral and cognitive symptoms of OCD. We used chronic treatment with the D2 and D3 dopamine receptor agonist quinpirole as a rat model of the disease. In this model, we examined changes in behavioral dynamics and, in a parallel experiment, changes in organization of neuronal activity in the hippocampus and anterior cingulate cortex (ACC). At the behavioral level, we observed increased locomotion and repetitive stereotypical trajectories in quinpirole-treated rats, with frequency of repetitions increasing over the course of the session. At the level of neuronal activity, a gradual increase in the firing rate of ACC neurons within a session paralleled the dynamics of behavioral stereotypy after quinpirole treatment. In quinpirole-treated rats, we observed increased stability in the temporal organization of hippocampal neuronal firing, but no increase in the stability of the spatial organization of discharge. The increased stability of hippocampal firing was observed at both the level of single neurons and coordinated activity of neuronal pairs, and was connected to modulation of activity by theta rhythm. Studying neuronal activity changes underlying behavioral and cognitive manifestations of brain disorders is crucial for understanding and treating brain pathologies.

We review clinical observations and experimental data to examine the pathophysiological mechanisms by which apnea of prematurity and intermittent hypoxemia destabilizes respiratory control and might lead to neurodevelopmental disorders. Clinically, both apnea and hypoxemia are characterized by marked heterogeneity in definitions, monitoring approaches, and temporal patterns, complicating comparisons across studies. Clinical evidence suggests that cumulative hypoxemic burden, rather than apnea duration alone, is a key determinant of respiratory and neurodevelopmental morbidity in preterm neonates. Repeated hypoxemia-reoxygenation cycles enhance peripheral chemoreceptor sensitivity, narrow the CO₂ reserve, and promote respiratory instability during a critical developmental window. Animal models of intermittent hypoxia demonstrate that this sensitization is mediated by reactive oxygen species (ROS) signaling and a metabolic response involving neuronal adenosine release, activation of xanthine oxidase and NADPH oxidase ultimately converging to inhibition of mitochondrial complex I and metabolic depression during the hypoxic phase. This response is clinically evidenced by a reduction of EEG amplitude occurring during apnea. We further propose that subtle changes in biochemical equilibrium within the Krebs cycle favor succinate accumulation during the hypoxic phase, which is then rapidly oxidized during the reoxygenation phase, leading to enhanced ROS production, as demonstrated in models of ischemia-reperfusion injury and neonatal severe hypoxia. We finally provide preliminary data showing that the succinate dehydrogenase inhibitor dimethyl malonate reduces oxidative phosphorylation in brain sample of mice pups, therefore establishing an experimental framework to directly address the hypothesis that succinate accumulation contributes to ROS synthesis in a rodent model of apnea of prematurity.

OBJECTIVE: 24h movement behavior, including physical activity (PA), sedentary behavior (SB), and sleep(SLP), is independently associated with health after stroke. Few studies have explored the trajectory of 24h movement behavior and its effect on functional recovery in stroke survivors. DESIGN: We conducted a prospective longitudinal study from November 2023 to June 2025. SETTING: This study was conducted in five hospitals in Henan province. PARTICIPANTS: The ActiGraph GT3X+ accelerometer was used to collect 24h movement behavior of 353 stroke survivors at acute phase(T0), 3-month recovery phase (T1), and 6-month sequelae phase (T2) after stroke onset, and functional recovery was evaluated at 12 months (T3) post-stroke. INTERVENTIONS: Patients' demographic information, disease-related data, psychological-related indicators and environment-related indicators were collected. MAIN OUTCOME MEASURES: The modified Rankin Scale (mRS) was used to assess their functional recovery 12 months after the onset of the disease. Through a prospective longitudinal study, Parallel-Process Latent Class Growth Model(PP-LCGM) was applied to determine the trajectories of 24h movement behavior, logistic regression was used to explore the effects of different trajectories on functional recovery. RESULTS: 298 stroke survivors completed three follow-up visits. Four potential categories of the 24h movement behavior change trajectory were finally identified. Multivariate logistic regression analysis showed that, after adjusting for age, gender, BMI, NRS grade, NIHSS score, BI index, social support, exercise self-efficacy, anxiety, and depression, there was an increased risk of poor prognosis in the 24h movement behavior imbalance group(OR:5.237,95%CI:1.848-14.835) or long-SLP increased-SB decreased-PA group(OR:4.160,95%CI:1.589-10.891) compared with the 24h movement behavior balance group. CONCLUSIONS: The results showed that stroke survivors had different 24h movement behavior trajectories after acute stroke, and there was an increased risk of poor prognosis in the 24h movement behavior imbalance group or long-SLP increased-SB decreased-PA group. 24h movement behavior interventions can be developed accordingly.

BACKGROUND: Toll-like receptors (TLRs) are key pattern-recognition receptors initiating inflammatory signaling, and their peripheral mRNA levels may reflect disorder-specific innate immune activation. Dysregulation of innate immunity has been implicated across schizophrenia spectrum disorders (SSD) and mood disorders, yet no quantitative synthesis of TLR expression has been available. METHODS: The review protocol was registered in PROSPERO (CRD420251146982). MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science were searched from the inception date to September 2025 for studies quantifying peripheral blood TLR1-TLR10 mRNA in SSD or mood disorders relative to healthy controls. Random-effects meta-analyses were performed using Hedges' g, along with sensitivity analyses and meta-regressions. RESULTS: Twenty-six studies met the inclusion criteria, comprising 678 individuals with SSD, 523 with mood disorders, and 1182 healthy controls. In SSD, TLR4, TLR8, and TLR10 showed significantly elevated expression (g = 0.26 - 0.31, p < 0.05). In mood disorders, TLR2, TLR5, and TLR6 were significantly upregulated (g = 0.23 - 0.32, p < 0.05). CONCLUSIONS: SSD and mood disorders are each associated with distinct patterns of elevated peripheral blood TLR expression relative to healthy controls. These disorder-specific patterns - a broader, multimicrobial profile in SSD versus a more restricted, predominantly antibacterial one in mood disorders - suggest partly distinct innate immunopathological pathways. The findings support the relevance of TLR-based immunophenotyping across diagnostic groups. Longitudinal, experimental, and multi-omics studies are needed to provide further mechanistic insights.