As virtual care becomes embedded in healthcare delivery, understanding the capabilities patients need to engage with these services is critical to safe, equitable access. This study aimed to identify patient capabilities for virtual care engagement described in existing guidance and support resources. Document analysis was used to examine patient-focused documents from Australia and New Zealand. A comprehensive search was conducted across the websites of 83 government departments, healthcare agencies, private healthcare organisations, and consumer organisations. Thematic framework analysis was applied to synthesise the findings. Three overarching capability themes with nine sub themes were identified: (1) Technology and Infrastructure (2) Literacy and Advocacy and (3) Service Engagement capabilities. Most documents prioritised technology and task-based engagement with limited attention to equity, advocacy, safety, privacy and support for priority groups. Findings highlight essential patient capabilities for virtual care and reveal important gaps. However, this study was limited to publicly available documents from two countries and may not fully capture informal or practice-based support available for virtual care use. Future research should examine how these capabilities are enacted in real-world settings and explore patient perspectives across diverse populations to inform more inclusive and equitable virtual care design.

Levetiracetam (LEV) is a widely used antiepileptic but associated with psychiatric side effects. While mild reactions are common, manic and psychotic episodes are less frequent, though clinically significant. This review critically assesses published cases of (hypo)manic and psychotic episodes related to LEV. A systematic review was conducted using MEDLINE (PubMed), Cochrane Library, and Web of Science (up to 1 June 2025), restricted to studies with primary clinical data on (hypo)manic or psychotic episodes associated with LEV. The quality of each case was assessed using a critical appraisal checklist, and the Naranjo Adverse Drug Reaction Probability Scale was applied to evaluate causality. A total of 50 cases met the inclusion criteria: Eight (hypo)manic and 42 psychotic episodes. The most frequent psychiatric manifestations were delusions (48%), aggressiveness (44%), and manic symptoms (38%). Temporal lobe epilepsy was present in 26% of patients, and 66% had uncontrolled seizures. Although case reports describe an association between LEV and (hypo)manic and psychotic episodes, causality assessment based on the methodological approach applied indicated a low probability that LEV alone was responsible. Alternative explanations, including epilepsy-related factors and comorbid medical conditions, were frequently cited. In some cases, an alternative diagnosis might be manic episode with psychotic features.

Extended duration of under-treated psychosis (DUP) is among the strongest predictors of poor outcome, yet diagnostic heterogeneity impedes treatment matching, with approximately 50% of patients failing to respond to first-line antipsychotics. Negative symptoms and cognitive impairment are particularly refractory, lacking effective pharmacological treatments. Identifying neurotransmitter systems associated with specific symptom dimensions could accelerate targeted therapeutic development and reduce DUP. We applied Partial Least Squares correlation (PLSc) to derive whole-brain resting-state functional connectivity (RSFC) and anatomical (cortical thickness and subcortical volume) signatures associated with five psychopathology dimensions (positive symptoms, negative symptoms, general psychopathology, mania, and cognition) in a transdiagnostic sample from the Human Connectome Project-Early Psychosis (HCP-EP; n=124). We tested associations with potential confounds including antipsychotic medication dosage and substance use. Signatures were spatially correlated with 21 Positron Emission Tomography (PET)-derived receptor and transporter maps across 9 neurotransmitter systems using the neuromaps toolbox. Significant RSFC signatures emerged for positive symptoms, negative symptoms, general psychopathology, and cognition, but not mania. The negative symptom RSFC signature correlated with norepinephrine transporter (NET; ρ=.40, q=.030) and vesicular acetylcholine transporter (VAChT; ρ=.38, q=.048) distributions. The cognition signature similarly correlated with VAChT (ρ=.48, q=.025). Anatomical signatures were associated with positive symptoms, general psychopathology, and cognition, but were more susceptible to confounding by medication and substance use. No significant receptor associations were detected for anatomical signatures. These findings implicate cholinergic and noradrenergic systems as molecular targets for negative symptoms and cognitive impairment, supporting prioritization of these systems in pharmacotherapy development in early psychosis.

This research aimed to examine the clinical relevance and biological function of the tight junction protein claudin-2 (CLDN2) in gastric cancer, along with its regulatory interactions with lymphoid enhancer-binding factor 1 (LEF1) and the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Analysis of CLDN2 expression and its prognostic implications in gastric cancer was conducted using data from the Cancer Genome Atlas (TCGA) database. The effects of CLDN2 or LEF1 on gastric cancer (GC) cells were detected by RT-qPCR, Western blot, cell-counting kit-8 (CCK-8), transwell assay, flow cytometry, CO-IP and immunofluorescence assays. The interactions between CLDN2 and LEF1 was predicted and validated using Gene MANIA and GEPIA. The functional association between CLDN2 and LEF1 was analyzed by rescue experiments. In GC tissues, CLDN2 was significantly upregulated and correlated with tumor stage, lymph node metastasis, and poor prognosis, showing elevated levels in young patients (21-40 years old) and individuals infected with Helicobater pylori (H. pylori). CLDN2 silencing inhibited GC cell proliferation, migration and invasion, induced G1-phase cycle block and apoptosis, and decreased cyclin D1 expression. CLDN2 and LEF1 were positively correlated and directly interacted, and suppressing LEF1 hindered the progression of GC. CLDN2 reduced KEAP1 expression and promoted NRF2 protein stability through post-transcriptional regulation. Silencing CLDN2 or LEF1 activated the KEAP1/NRF2 pathway and inhibited downstream p65, IkappaB kinase (IKK) and IκB protein expression. Reducing LEF1 levels counteracted the effects of CLDN2 on GC cell growth and KEAP1/NRF2 pathway. Increased levels of CLDN2, which modulate the LEF1 and KEAP1/NRF2 pathways, are correlated with GC progression and may be used as a marker for poor prognosis.