Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 30% of adults, with about 30% of cases progressing to metabolic dysfunction-associated steatohepatitis (MASH), which can lead to cirrhosis and hepatocellular carcinoma. Cardiovascular disease is the leading cause of death in patients with MASH, highlighting the need for integrated heart-liver co-management. MASLD and cardiovascular disease share common pathophysiological mechanisms, including insulin resistance, low-grade inflammation, atherogenic dyslipidaemia, and oxidative stress, creating a bidirectional interplay that drives disease progression. Effective management of MASLD requires addressing not only hepatic steatosis, inflammation, and fibrosis, but also managing cardiovascular risk. Current clinical practice and trials face several challenges, including the underdiagnosis of MASLD, poor collaboration between hepatologists and cardiologists, and a paucity of pharmacological options that safely target both the liver and heart. This Review covers three main pharmacological approaches: metabolic-targeted therapies, which improve the upstream metabolic milieu; liver-targeted therapies, which focus on MASH and fibrosis, but require further evaluation for cardiovascular safety; and cardiovascular therapies, which might provide hepatoprotective effects, but need further study. This Review discusses the benefits and limitations of these pharmacotherapies, emphasising the importance of an integrated heart-liver co-management approach to improve clinical outcomes for patients living with MASLD.

Selective enrichment of submicron pathogens (e.g., bacteria, viruses) from complex matrices containing larger interferents remains a fundamental challenge in rapid biosensing. Conventional thermophoresis-based methods suffer from inherent size-dependent limitations and require fluorescent labeling for specificity, compromising clinical utility. Here, we propose a new strategy by exploiting density-manipulated sedimentation to break this limitation, enabling the selective enrichment of 200 nm targets from 1.3 μm interferents within 15 min. Through aptamer-directed in-situ synthesis of plasmonic nanoparticles (AgNPs) on target pathogens, we increase the apparent density of the targets, while simultaneously covering them with surface-enhanced Raman substrates. When coupled with laser-induced convection, the approach enables label-free detection of target bacteria at clinically relevant concentrations in blood serum with coexisting bacteria, as well as in clinical samples. The synergy of density-enhanced sedimentation and convection competition establishes a new microfluidic principle for particle manipulation. This work not only overcomes a critical bottleneck in point-of-care diagnostics but also provides a versatile platform for the rapid biosensing of diverse pathogens.

Symptomatic non-acute internal carotid artery occlusion (NA-ICAO), particularly Hasan type A/B, is characterized by persistent cerebral hypoperfusion that may lead to neurological and cognitive impairment. Endovascular recanalization therapy (EVT) aims to restore cerebral blood flow and improve functional outcomes in patients with these conditions. A total of 66 patients with symptomatic NA-ICAO admitted between June 2022 and October 2023 were randomly assigned to an EVT group (n = 32) or a conservative medical therapy group (n = 34). Neurological and cognitive functions were evaluated before treatment and at 3 and 12 months after treatment using standardized scales, including the modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). Recanalization was successfully achieved in all 32 patients, with 9 cases reaching TICI grade 2b and 23 cases reaching TICI grade 3. Among 32 patients undergoing EVT, 12 (37.5%) experienced perioperative adverse events, including 2 (6.25%) serious events. At 3 months, the mRS score was significantly lower in the EVT group than in controls. At 12 months, the EVT group showed significantly greater improvements in MMSE, mRS, and MoCA scores, with the largest effect size observed for MoCA (Cohen's d = 0.82). Domain-specific analysis revealed significant improvement in language ability. EVT may offer potential clinical benefits for selected patients with chronic carotid occlusion; however, larger multicenter studies are warranted to confirm its long-term efficacy and safety.

Handgrip strength is a proxy for muscular fitness, an indicator for general health status, and is associated with cardiometabolic health. The mechanisms connecting handgrip strength to skeletal muscle function are incompletely understood. We applied integrated linkage-disequilibrium (LD)-adjusted colocalization analysis of genome-wide association study (GWAS) summary statistics for handgrip strength combined with expression and splicing quantitative trait loci from skeletal muscle and identified Glycogen branching enzyme 1 (GBE1) as a candidate gene for handgrip strength. CRISPRi knockdown of GBE1 in immortalized human skeletal muscle cells (HMCL-7304) demonstrated decreased glycogen content and accumulation of polyglucosan bodies. Knockdown of GBE1 led to increased oxygen consumption rate, oxidative stress, and changes in mitochondrial morphology. Transcriptomic profiling of GBE1 knockdown cells identified up-regulation of the human superoxide dismutase 2 (SOD2) and enrichment of pathways related to muscle contraction and oxidative stress responses. These functional genomic analyses prioritize GBE1 as a muscle-relevant candidate gene for handgrip strength and provide mechanistic insights to muscle fitness.

Objective To evaluate the characteristics of psychotropic medication use under pro re nata (PRN, or "as needed") orders for patients treated in a psychogeriatric hospital ward. Design A retrospective point-prevalence, cross-sectional study comparing PRN order parameters with standards published by the Australian Commission on Quality and Safety in Health Care. Setting An inpatient psychogeriatric unit in a South Australian public teaching hospital. Participants Data were collected from inpatient charts and case notes during a single, continuous 24-hour sampling period. All PRN medication orders were reviewed, including documentation of actual drug administrations, and these were matched with the associated clinical outcomes. Data were collected from 26 patients, for whom a total of 38 PRN psychotropic medication orders were analyzed. Result The majority of PRN orders (81%) met the criteria of the relevant Australian National Standards; however, of the 19 medication administration occasions, only 26% had adequate documentation that included both specific reasons for administration and the outcomes associated with the PRN treatment. Overall, it was noteworthy that a relatively high proportion of these PRN orders (61%) were actioned during the 24-hour snapshot period. Conclusion The use of PRN psychotropic medications remains an important component in the treatment of older patients with mental illness. Continued efforts to improve and optimize the documentation associated with PRN psychotropic drug administration warrant ongoing attention.

The self and its disorders in schizophrenia have been studied extensively over recent decades. Much of this literature is grounded in a bipartite understanding of the self, distinguishing the pre-reflective, minimal self from the reflective, narrative self. However, few studies have systematically examined the links between disturbances at these two levels of self. This integrative review addresses this gap by analyzing both theoretical and empirical contributions. Three theoretical models are described. The Structural model posits that minimal self-disorders hierarchically give rise to narrative self-disturbances and the schizophrenia phenotype, with a primarily pathogenic focus. The Dialectical model emphasizes reciprocal interactions between minimal and narrative self-disturbances, generating the schizophrenia phenotype with both pathogenic and salutogenic implications. The Contextual model highlights social, territorial, and biological dimensions of the self and its disorders in context. Empirical studies specifically addressing the mechanistic links between minimal and narrative self-disturbances remain scarce and preliminary. Overall, the literature appears preliminary and occasionally speculative, yet it suggests several promising avenues for future research and clinically relevant applications. This article is categorized under: Philosophy > Consciousness Psychology > Theory and Methods.

Agentic artificial intelligence (AI) represents a pivotal shift in clinical decision support, moving beyond static tools by reasoning, adapting, and acting alongside clinicians. Psychiatry, grounded in subjective experience, trust, and longitudinal care, offers both an opportunity and a high-stakes testbed. Agentic systems may enhance documentation, personalize care, support continuous monitoring, and extend access, while raising risks around bias, explainability, privacy, and therapeutic alliance. In this Perspective, we (i) define psychiatry-specific agentic AI distinct from decision-support and fully autonomous systems; (ii) synthesize current evidence across studies; (iii) propose assistive, collaborative, and semi-autonomous roles; and (iv) outline a roadmap for responsible implementation.

Migrants assuming caregiving roles for other migrants require care themselves. We report on how migrants in South Africa navigate the dual responsibilities of caregiving and self-care. 15 semistructured interviews were conducted with migrant caregivers between January and June 2023. Data were thematically analysed and interpreted through a narrative lens. Findings highlight the critical role migrant caregivers play in offering support to their communities. Despite systemic challenges, including language barriers, exclusion and personal trauma, they foster community cohesion and emotional well-being. At the heart of acts of care exists an ambivalence between identity management and the experience of trauma and exclusion.

The FR-IC index demonstrated good concurrent validity for baseline disability and significant predictive validity for 1-year deterioration in disability among older outpatients. This tool may enable effective risk stratification and seamless monitoring of physical and mental capacities across the aging trajectory in clinical settings.