Cardiac hypertrophy is a major pathological response to cardiovascular stress and a critical contributor to heart failure (HF). Gentiopicroside (GPS), a naturally occurring iridoid glycoside derived from Gentiana scabra, exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties. However, its role and molecular mechanisms in cardiac hypertrophy and HF remain unclear. A pressure overload-induced cardiac remodeling model was established in C57BL/6 mice by transverse aortic constriction (TAC), followed by GPS treatment with or without the EGFR tyrosine kinase inhibitor Canertinib. Cardiac function and remodeling were evaluated by echocardiography, hemodynamic analysis, and histological staining. In vitro, neonatal rat ventricular myocytes (NRVMs) and cardiac fibroblasts (NRCFs) were used to investigate the cellular effects of GPS. EGFR knockdown, conditioned medium transfer, cellular thermal shift assay (CETSA), and lysosomal/proteasomal inhibition experiments were performed to elucidate the mechanism underlying GPS-mediated EGFR regulation. GPS markedly alleviated TAC-induced cardiac hypertrophy and fibrosis in vivo and suppressed Ang II-induced cardiomyocyte hypertrophy. GPS also reduced cardiomyocyte apoptosis and oxidative stress. Mechanistically, GPS acted as an EGFR degrader rather than a conventional kinase inhibitor, reducing total EGFR abundance without inhibiting the kinase activity of remaining receptors, thereby attenuating excessive AKT/ERK1/2 signaling. CETSA and molecular docking indicated direct GPS-EGFR interaction. GPS-induced EGFR reduction was mediated primarily through lysosomal degradation, as demonstrated by chloroquine rescue experiments, whereas proteasome inhibition had limited effects. Co-administration of Canertinib with GPS conferred no additional benefit. EGFR depletion abolished the protective effect of GPS in cardiomyocytes, indicating a cardiomyocyte-autonomous mechanism. This study identifies GPS as a regulator of EGFR stability during pathological cardiac remodeling. By promoting lysosome-dependent EGFR degradation and suppressing excessive AKT/ERK1/2 signaling, GPS attenuates cardiac hypertrophy and remodeling while preserving basal EGFR function, highlighting its potential therapeutic value for HF.

Increasing life expectancy has led to a growing prevalence of age-related disorders, including dementia, cardiovascular disease, frailty, osteoporosis, sarcopenia, and cancer. Heme oxygenase-1 (HO-1), a stress-inducible enzyme that degrades heme into carbon monoxide (CO), biliverdin which is then reduced to bilirubin by the biliverdin reductase enzyme, and iron, has emerged as a key regulator of several hallmarks of aging, including oxidative stress, inflammation, autophagy, mitochondrial dysfunction, and cellular senescence. This review evaluates age-associated changes in HO-1 expression across major organs and examines the roles of HO-1 and its metabolites in age-related diseases, with particular emphasis on dementia and cardiovascular disorders. Current evidence suggests that the biological effects of HO-1 depend not only on expression level but also on temporal regulation, tissue specificity, and the balance between protective and deleterious downstream pathways. Future research should focus on defining physiological and therapeutic ranges of HO-1 activity in different tissues, sexes, and stages of aging, while clarifying the distinct contributions of CO, bilirubin, and iron metabolism. Such studies may enable precision-medicine approaches that harness HO-1 modulation to promote healthy aging and prevent age-related diseases.

This study analyzes changes in distance travelled by Illinois youth ages 5-17 between 2016 and 2024 for mental health hospitalizations at Illinois hospitals.

We obtained records for admissions with a mental health principal diagnosis in each year. Patient and hospital zip codes were used to estimate distance. We present bivariate and multivariable analyses of change in distance between years by patient and hospital characteristics.

There were 22,516 youth mental health admissions in 2016 to 101 hospitals and 18,316 in 2024 to only 56 hospitals. Hospitalizations of youth who travelled ≥50 miles increased from 15.7% in 2016 to 21.9% in 2024 (p<0.001). Youth who were younger, non-Hispanic White, covered by Medicaid and those from 'downstate' Illinois counties had the longest travel distances. Travel distance ≥50 miles for youth hospitalized for depression increased from 15.4% in 2016 to 23.8% in 2024. As compared to 2016, the adjusted odds of youth having to travel more than 50 or 100 miles in 2024 were 1.76 (95% CI=1.36-2.28) and 2.05 (95%CI=1.30-3.24) respectively.

By 2024, more than one in five children traveled ≥50 miles and one in ten traveled ≥100 miles to access mental health hospital care. The odds of travel ≥100 miles more than doubled between 2016 and 2024. The increase in travel distance appears to be related to a large reduction in admissions to community hospitals with a small number of 2016 admissions, with a corresponding trend towards hospitalizations at a small number of specialty behavioral health hospitals.

Objective: To explore college student-athletes' preferences and perceived needs for online mental health interventions. Participants: 772 collegiate athletes based in the United States. Methods: Mixed-methods, comprising a cross-sectional survey and focus groups. The survey assessed athletes' current and lifetime mental health diagnoses, mental health literacy, help-seeking intentions, and program preferences, with a focus on gender differences. Focus groups provided insights into participants' experiences and expectations for interventions Results: Athletes expressed a strong preference for mental health programs that emphasize practical skills, are self-paced, and digital-first interventions with interactive components. Intentions were highest for seeking help from peers and family members. Stigma and confidentiality concerns emerged as major barriers to engagement. Men reported lower interest in almost all mental health topics, and higher intentions to not seek help from anybody for mental health problems. Conclusion: These findings highlight the need for athlete-centered, gender-sensitive mental health programs that are accessible and engaging.

Brain-computer interface (BCI) systems combined with motor imagery (MI) have emerged as promising tools in neurorehabilitation. Real-time neurofeedback may further enhance motor recovery by promoting use-dependent neuroplasticity; however, evidence in chronic stroke remains limited, particularly from controlled pilot studies.

This case series explored the feasibility and preliminary effects of EEG-based BCI neurofeedback combined with MI and physiotherapy on upper-limb motor function and brain activation patterns in individuals with chronic stroke.

In a double-blind, controlled protocol, seven individuals with chronic stroke were allocated to either an experimental group receiving MI with real-time EEG-based BCI neurofeedback or a control group receiving MI with sham feedback. All participants completed a standardized four-week physiotherapy program. Motor outcomes were assessed with the Action Research Arm Test, Fugl-Meyer Assessment, Motor Assessment Scale, and grip strength, with functional changes interpreted against minimal clinically important difference (MCID) thresholds. Neuroplastic changes were explored using EEG-derived symmetry measures and task-related functional MRI.

Participants receiving real neurofeedback exhibited consistent improvements exceeding MCID thresholds in at least one functional outcome, most notably grip strength. This group also demonstrated more symmetrical EEG activity and more consistent sensorimotor and cerebellar activation patterns on fMRI. In contrast, responses in the sham group were more variable and appeared influenced by a single high responder.

These findings support the feasibility of integrating EEG-based BCI neurofeedback with MI and physiotherapy in chronic stroke rehabilitation. The observed functional gains and associated neurophysiological changes suggest a preliminary, exploratory role for this intervention in promoting upper-limb recovery in this small sample.

Biofluid proteins are promising transdiagnostic markers for delineating disease heterogeneity in psychosis. This study examined proteomic profiles in a transdiagnostic early psychosis sample to test the hypothesis that psychosis is associated with proteomic signatures of premature aging. We analyzed proteomic data from 85 individuals with early psychosis and 35 healthy controls from the Human Connectome Project for Early Psychosis (HCP-EP), using the Olink platform across four validated panels (Cardiometabolic, Inflammation, Cardiovascular II, and III). Our dual analytic strategy included: (1) calculating an index based on senescence-associated secretory phenotype (SASP) proteins to assess cellular aging, and (2) analyzing all 374 proteins using Gene Set Enrichment Analysis to identify whether predefined biological pathways are collectively enriched. We compared the SASP index and enriched pathways between groups and examined associations with sociodemographic, physical health, cognitive, psychological well-being, psychosocial functioning, symptom, and medication data. The SASP index was significantly elevated in the psychosis group. Pathway analyses revealed enrichment of two inflammation-related pathways in psychosis after multiple comparison correction: Cellular Response to Tumor Necrosis Factor and Monocyte Chemotaxis. The higher SASP index and the enriched inflammatory pathways were associated with increased body mass index (BMI) and reduced psychological well-being. Our findings are consistent with prior research linking psychosis to premature aging and an increased inflammation response. They also underscore the value of examining multiple biomarkers and biological pathways simultaneously and highlight the importance of conceptualizing psychosis as a whole-body condition. However, given the sample size, results should be considered preliminary. Larger, longitudinal studies are needed to track proteomic changes over time and assess the predictive value of these biomarkers for identifying vulnerable individuals and clinical outcomes.

First-episode psychosis (FEP) may result from a variety of secondary etiologies, making lumbar puncture (LP) for cerebrospinal fluid (CSF) investigations an important diagnostic consideration in this context. However, the lack of high-quality evidence on the prevalence of clinically-relevant CSF abnormalities hampers clinical consensus on when to pursue LP in FEP.

Determine a meta-analytic estimate of the prevalence of clinically-available CSF abnormalities in FEP.

Electronic databases Ovid MEDLINE, Embase, PsycINFO, and Web of Science were searched from inception to October 2024. References of included articles were also screened.

We included studies that performed LP on a cohort of FEP and reported results of clinically-available CSF analysis, enabling prevalence-estimates of abnormalities.

Data was extracted following PRISMA and MOOSE guidelines. Pooled prevalences were calculated by random-effects models. Moderators were tested using meta-regression analysis, and heterogeneity assessed by I² index.

Prevalence of clinically-available CSF abnormalities, focusing on clinically-relevant markers and number needed to assess (NNA).

Thirty-seven papers comprising 3,330 FEP patients who underwent LP were included, allowing calculation of prevalence estimates for 14 clinically-available CSF abnormalities. Of clinically-relevant abnormalities, the prevalence of CSF-restricted oligoclonal bands (OCB2) was 7.1% (95% CI 3.3-12.0, NNA 14), pleocytosis was 3.2% (95% CI 2.1-4.4, NNA 31) and anti-NMDAR antibodies was 2.3% (95% CI 0.1-6.4, NNA 43). Subgroup analysis showed that anti-NMDAR antibodies were mainly detected in studies that selected patients with high suspicion of secondary causes and were low in studies which excluded patients with a high index of suspicion of a secondary cause, based on clinical and ancillary testing. OCB2 was detected at appreciable prevalence in both the high-suspicion and low-suspicion subgroups; a high-suspicion subgroup estimate could not be derived for pleocytosis.

The most common clinically-relevant CSF abnormality, CSF-restricted oligoclonal bands, had a pooled prevalence of 7.1%, similar to the reported prevalence of a clinically-relevant abnormality on brain MRI. The probability of detecting an abnormality was higher among patients with a high index of suspicion for a secondary cause, and this was most marked for anti-NMDAR antibodies. However, few included studies reported healthy controls, and none explicitly tested whether presence of these abnormalities alter treatment response or outcomes, so the specificity and treatment implications of these findings for psychosis will benefit from future research.

Impulsivity is frequently examined in relation to adolescent non-suicidal self-injury (NSSI), yet the strength of this association remains unclear because findings vary across studies. This study quantified the association and examined potential sources of heterogeneity.

A three-level random-effects meta-analysis of 37 studies (N = 69,572) accounted for hierarchical dependencies among effect sizes. Potential moderators included assessment modality (self-report scale, semi-structured interview, or neurocognitive task), specific measurement instrument, impulsivity domain, sample source, and psychiatric comorbidity.

Impulsivity was significantly associated with NSSI severity (d = 0.46) and was higher among adolescents with NSSI than controls (d = 0.37). Effect sizes varied significantly across specific impulsivity measurement instruments after FDR correction. In contrast, the omnibus test of broader assessment modalities was nonsignificant. Separately, self-report scales yielded a significant pooled estimate (d = 0.48), whereas neurocognitive tasks yielded a small and nonsignificant estimate (d = 0.11); these subgroup estimates do not establish modality differences. Neither sample source nor psychiatric comorbidity significantly moderated the association. Trait and symptom-level impulsivity yielded significant pooled estimates (d = 0.48 and 0.40, respectively). Negative urgency showed a relatively large pooled estimate (d = 0.60) based on only four effect sizes.

Several moderator estimates were based on few effect sizes, limiting their precision.

Impulsivity is an important but nonspecific correlate of adolescent NSSI. Heterogeneity was more consistently associated with specific measurement instruments, highlighting measurement specificity when interpreting the impulsivity-NSSI literature. Self-report and neurocognitive measures may capture partly different aspects of impulsivity, warranting further multimethod research.

Transcranial alternating current stimulation (tACS) provides promising evidence as a technology to modulate brain oscillations. Individualized brain oscillation measures from magnetoencephalography (MEG) or electroencephalography (EEG) (M/EEG) can optimize frequency, location (montage), and timing of tACS. This systematic review aims to comprehensively characterize the parameter space and outcomes of M/EEG-informed personalized tACS interventions.

We conducted a systematic review of the literature up to January 2024, per PRISMA guidelines. The pre-registered search strategy combined terms related to M/EEG and tACS. Any study that utilized M/EEG-informed individualized tACS intervention was included, and relevant variables were extracted.

Seventy-eight publications comprising 143 distinct experiments were identified, including 128 EEG-informed and 15 MEG-informed studies. Frequency-based individualization was predominant (93%), followed by timing-based (4.2%; stimulation onset or phase) and montage-based (2.8%) methods. The most frequently individualized frequency band was alpha (69.2%), followed by theta (15.4%), gamma (5.6%), beta (4.9%), delta (2.1%), and dual-frequency protocols (2.8%). Outcome measures most commonly assessed physiological changes (28.7%) and cognitive functions, particularly perception (18.9%) and memory and learning (17.5%). 77.9% of sham-controlled experiments reported significant positive outcomes, compared to 56.2% of those with active control.

Over the past decade, personalized M/EEG informed tACS trials provide growing evidence for effectiveness of this technology in engaging brain oscillations. This systematic review highlights key methodological parameter space in this technology and its outcomes. It also provides a roadmap for future trials with rigorous active control arms to optimize engaging brain oscillations and impacting cognitive functions and clinical outcomes.

Work-related stress is a growing concern among healthcare professionals, with potential adverse effects on psychological well-being and quality of care. Midwifery practice, characterised by high emotional demands and frequent exposure to critical events, may increase vulnerability to occupational stress and psychological distress. This study aimed to evaluate perceived stress and psychological well-being among italian midwives and to compare hospital-based and community-based settings. We conducted a cross-sectional multicentric observational study on 175 midwives (140 hospital-based; 35 community-based). Perceived stress was assessed using the 10-item Perceived Stress Scale (PSS-10), and psychological well-being was evaluated with the Psychological General Well-Being Index (PGWBI). Hospital-based midwives reported significantly higher perceived stress than community-based midwives. A significant negative correlation between perceived stress and psychological well-being was found in both groups, with a stronger association observed in the hospital setting. The work setting significantly influences midwives' mental health, with hospital practice associated with higher stress and lower psychological well-being. These findings emphasize the urgent need for tailored organizational support, structural interventions, and policy initiatives to safeguard midwives' psychological health and enhance workforce retention.