Accurate diagnosis of dementia with Lewy bodies (DLB) remains challenging, with misdiagnosis potentially leading to harmful treatment decisions. DOPA decarboxylase (DDC) shows promise as a cerebrospinal fluid (CSF) biomarker for DLB and Parkinson's disease (PD), but quantitative assays are needed for its clinical implementation. Here we report on the development of two DDC immunoassays and the extensive clinical validation of DDC across three clinical cohorts (n = 740), one biologically defined cohort (n = 253), one cohort with detailed dopamine transporter imaging information (n = 102) and one autopsy-confirmed cohort (n = 78). CSF DDC levels were significantly higher in DLB and PD (up to 2.5-fold versus controls; 1.9-fold versus AD), showing area under the curve values > 0.9 for differential diagnosis. Elevated CSF DDC was linked to the presence, but not severity, of motor impairment. In autopsy-confirmed DLB, higher CSF DDC correlated with progressing α-synuclein pathology and immunohistochemistry in DLB and PD brain tissue revealed colocalization of DDC and α-synuclein in the substantia nigra. These findings underscore DDC's value to support DLB and PD diagnosis, paving the way for its clinical implementation using the here-presented developed immunoassays.

The objective of this study was to investigate the effects of rituximab (RTX) intrathecal injection on antibody levels in serum and cerebrospinal fluid (CSF), hippocampal tissue and neuronal injury and the behaviour of central neuropsychological lupus erythematosus (cNPSLE) model mice and to further explore the effects of RTX on microglia (MG) polarisation and related signalling pathways.

Female MRL/lpr mice received intrathecal RTX, with C57BL/6 and MRL/mpj mice as controls. Behavioural performance was evaluated using the open field test, novel object recognition and Porsolt swim task. Autoantibody levels in serum and CSF were measured by ELISA. Hippocampal pathology was assessed by H&E and Nissl staining. M1-type MG activation (Iba-1⁺/CD32⁺), CD20⁺ B-cell infiltration and immunoglobulin G (IgG) deposition were examined via immunohistochemistry and immunofluorescence. Immune transcriptome sequencing and in vitro polarisation assays were used to identify regulatory pathways.

Intrathecal injection of RTX reduced the levels of antibodies in the serum and CSF of MRL/lpr mice and alleviated brain tissue injury and neuronal injury. Moreover, hippocampal MG M1 polarisation was inhibited, and the number of CD20⁺ B cells and expression of IgG were reduced. Transcriptome sequencing revealed that the cAMP-dependent protein kinase A (cAMP/PKA) pathway may be involved in the activation of M1-type MG in the hippocampus. In vitro cell experiments demonstrated that RTX could reduce the expression of kinase cAMP-activated catalytic subunit alpha and phosphorylated-cAMP response element-binding protein/cAMP response element-binding protein through the suppression of the cAMP/PKA pathway, thus inhibiting M1-type MG activation.

The data in this study revealed that the intrathecal injection of RTX can attenuate M1-type MG activation-mediated inflammatory neuronal injury in cNPSLE model mice.

Preeclampsia is a pregnancy-specific multisystem disorder. With a global incidence of 2%-8%, preeclampsia is a major contributor to maternal and neonatal morbidity and mortality. The pathogenesis of preeclampsia is commonly described by a two-stage model. The first stage involves defective placentation in early pregnancy, marked by insufficient extravillous trophoblast invasion, impaired spiral artery remodeling, dysregulated sphingolipid metabolism, and an imbalance in immune tolerance; these anomalies lead to placental ischemia and hypoxia. The second stage consists of systemic maternal responses in the mid-to-late gestation period, including angiogenic imbalance, systemic inflammation, and endothelial dysfunction, which manifest as the clinical symptoms. Recent advances in multi-omics technologies and liquid biopsy have accelerated the discovery of novel biomarkers enabling non-invasive early prediction. Emerging therapeutic strategies target key pathological pathways: low-molecular-weight heparin to restore angiogenic balance and reduce inflammation, complement system inhibitors to counter aberrant activation, and epigenetic modulators to ameliorate endothelial dysfunction. Despite this progress, significant challenges remain, including the heterogeneity of preeclampsia, limited clinical validation of biomarkers and therapeutic targets, and the management of long-term cardiovascular sequelae. Future research should prioritize developing precision prediction models, conducting large-scale clinical trials for targeted therapies, and establishing comprehensive postpartum follow-up systems to improve the prevention, diagnosis, and treatment of preeclampsia.

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.