Exercise is increasingly acknowledged as an effective intervention for depression, yet the biological mechanisms underlying its antidepressant effects remain incompletely defined. Conventional models have emphasized brain-centered pathways, including BDNF signaling, monoaminergic modulation, hypothalamic-pituitary-adrenal axis regulation, hippocampal neurogenesis, and synaptic plasticity. These mechanisms are important, but they may not fully explain depression phenotypes characterized by elevated inflammatory burden, fatigue, anhedonia, diminished motivation, psychomotor slowing, cognitive inefficiency, and altered peripheral immune activity. This review proposes that exercise-induced lactate should be considered not only as a metabolic substrate or byproduct, but also as a dynamic immunometabolic signal. Appropriately dosed exercise can generate a transient and recoverable lactate pulse that may be detected by immune, vascular, and brain-associated cells through hydroxycarboxylic acid receptor 1, also known as HCAR1 or GPR81. We propose that the lactate-HCAR1 axis could represent a candidate mechanism linking exercise metabolism to bone marrow myeloid regulation, peripheral inflammatory tone, brain vascular and border interfaces, glial responses, and inflammation-related depressive symptom dimensions. The framework integrates skeletal muscle metabolism, myelopoiesis, peripheral myeloid cells, blood-brain interfaces, microglia, astrocytes, and endothelial cells into a cross-organ model of exercise psychiatry. Importantly, the strength of evidence differs across this pathway: some components are supported by human exercise physiology or preclinical causal studies, whereas others remain inferential and require validation in patients with depression. We therefore frame lactate-informed exercise prescription as a testable translational hypothesis rather than a clinically established strategy. Future studies should examine lactate kinetics, inflammatory biomarkers, immune cell phenotypes, symptom dimensions, safety, recovery dynamics, and comparisons with conventional heart-rate-, VO2-, or perceived-exertion-based prescriptions. If validated, this framework may help identify which patients benefit from exercise, which biological responses are meaningful, and how exercise can be studied as a quantifiable immunometabolic intervention.
Most United States children with neurodevelopmental disorders have not received genetic testing aligned with current guidelines. Integration of genetic counselors into non-genetics departments is a potential strategy to improve uptake, but prevalence and details of integrated care models are unknown. To characterize availability, utilization, and perceived need for genetic counselors across non-genetics departments caring for patients with neurodevelopmental disorders. Cross-sectional observational department-level survey. Child neurology, adult neurology, developmental pediatrics, child psychiatry, and adult psychiatry departments at Intellectual and Developmental Disabilities Research Centers. The survey was distributed to 67 departments across 15 institutions. The departmental response rate was 52% (35/67), with at least one response from 87% (13/15) of institutions. Presence/absence of dedicated genetic counselor(s), where "dedicated" was defined as hired by the department. This was a descriptive study only, with no comparative statistical analyses due to the exploratory nature. One third of departments (34%; 12/35) reported having dedicated clinical genetic counselors. Prevalence was highest in child neurology (67%; 8/12), followed by adult neurology (40%; 2/5) and developmental pediatrics (22%; 2/9), with none in child psychiatry (0/7) or adult psychiatry (0/2). In almost all departments with genetic counselors (92%; 11/12), they directly billed for their services, which universally included pre-test counseling/consent and post-test counseling. In departments without genetic counselors, only 39% (9/23) reported providers ordered their own genetic testing. Among all departments, over half (57%) were interested in adding/increasing genetic counseling support, while 26% were unsure and 17% uninterested. Insufficient funding was the most cited barrier; only one department reported insufficient need. Though currently implemented in only one third of departments, our findings suggest those with dedicated genetic counselors directly pursue genetic testing (without referring to genetics) more than those without genetic counselors. Interest in increasing or adding genetic counseling support was high, and though funding was a reported barrier, feasible funding models were described. In the context of limited medical geneticists and expanding precision therapies, alternate delivery models for neurodevelopmental genetic testing including genetic counselor integration in non-genetics departments may help to scale and sustain uptake.
Personality disorders (PDs) are increasingly recognized and highly prevalent, yet remarkably poorly understood, diagnosed and treated mental conditions. Common PDs include antisocial, avoidant, borderline, dependent, histrionic, narcissistic, obsessive-compulsive, and paranoid disorders. Experimental (animal) models are a valuable tool to study various brain disorders, including PDs. However, characterized by complex and frequently overlapping aberrant behaviors, PDs pose major challenges for their preclinical modeling. Here, we discuss the potential utility of zebrafish (Danio rerio) as complementary translational models relevant to studying PDs. Paralleling clinical symptoms and traits of PDs to specific behavioral phenotypes, biomarkers and paradigms in these fish, we critically evaluate the existing challenges and limitations of such models, and provide a conceptual framework for further research in this field. Despite these conceptual and practical challenges, we argue that zebrafish models not only provide a powerful platform for elucidating neurobiological mechanisms of a wide range of key PD traits (e.g., impulsivity, aggression, emotional dysregulation), but may markedly accelerate both translational modeling of these disorders and therapeutic discovery.
Protein S-palmitoylation is a dynamic and reversible post-translational modification (PTM) that governs diverse cellular processes, yet its study remains constrained by the indirect and ensemble-averaging nature of classical biochemical assays. Here, we report a nanopore-based platform, PALM-Scan (palmitoylation analysis via label-free monitoring and signature capture on nanopore) that directly transduces physicochemical signatures of S-palmitoylated peptides into digital electrical signals. Using an engineered Mycobacterium smegmatis porin A (M2-MspA) nanopore, PALM-Scan enables sequence-independent identification of S-palmitoylation and simultaneously differentiates S-palmitoylation from other cysteine-directed PTMs, including S-nitrosylation and S-glutathionylation, without probes or enrichment. We further demonstrate its translational potential by successfully detecting and distinguishing S-palmitoylated subpopulations of disease-relevant biomarkers, including mouse beclin-1 (BECN1)- and glial fibrillary acidic protein (GFAP)-derived peptides, in complex mixtures with minimal sample input. In summary, by integrating label-free operation, single-molecule resolution, and multiplex discrimination, PALM-Scan provides a transformative tool for interrogating S-palmitoylation dynamics in both basic research and biomedical applications.
The insular cortex has become an increasingly important focus of neuroscientific research because of its broad involvement in psychological and behavioral processes and its dysfunction in neuropsychiatric, developmental, degenerative and metabolic disorders. The insula is easily imaged in the human brain and is also a key target for both fundamental and translational studies in nonhuman animals. However, owing to a dearth of truly comparative studies on the insula, the extent to which this region shares structural and functional homologies between humans, monkeys and rodents remains incompletely understood. Here, we systematically evaluate current knowledge regarding homologies in the insula among model species and humans. We examine the strengths and limitations of various laboratory species for investigating the insula, and discuss how these factors influence the interpretation of findings and their application to the human insula. Finally, we propose research directions aimed at strengthening translational insula research and enhancing our understanding of cross-species similarities and differences.
Non-invasive brain stimulation (NIBS) techniques are increasingly used to modulate brain activity in basic and translational research. Kilohertz transcranial magnetic perturbation (kTMP) is a recently developed NIBS approach that uses magnetic induction to generate subthreshold electric fields in the brain. kTMP has been shown to modulate cortical excitability while producing no perceptible sensation at the stimulation site. However, its safety and tolerability have not yet been systematically evaluated-a gap this study aims to address.
Approach: We conducted sham-controlled experiments, within-subject comparisons, and patient feasibility studies with kTMP, entailing 433 sessions across 143 individuals. Participants rated annoyance, muscle activation, and pain on a 0-10 scale after each session. With primary motor cortex (M1) as the target, we compared active stimulation (~8 V/m cortical field) to sham (0 V/m) in healthy adults and chronic stroke patients. In healthy adults, we compared active vs. sham stimulation applied to dorsolateral prefrontal cortex, superior temporal gyrus, and cerebellum. Additional datasets examined tolerability across active kTMP parameters and multi-session feasibility in stroke patients. Safety monitoring included continuous observation for abnormal motor activity and EMG recording in initial experiments.
Main results: No adverse events occurred across 433 sessions. EMG monitoring revealed no artifacts, and no participants exhibited involuntary muscle contractions or signs of abnormal cortical excitation. kTMP was well tolerated, with mean ratings for active and sham stimulation remaining below 1.5 (where "2" indicates just-noticeable sensation). Permutation tests showed no significant active-sham differences and bootstrapped 95% confidence intervals consistently fell within the ±1 equivalence margin. When auditory masking was used, participants could not distinguish active from sham stimulation.
Significance: kTMP achieves cortical E-fields an order of magnitude higher than conventional subthreshold tES while maintaining robust safety margins and tolerability indistinguishable from sham, supporting its use for rigorous double-blind studies and translational settings.


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Current rodent models for anxiety and depression assessment face methodological challenges compromising both scientific rigor and animal welfare. This study introduced a novel approach using the Lévy flight (LF) statistical method to analyze spontaneous movement in open spaces. We employed three models: Chronic unpredictable mild stress (CUMS), Electric shock stress (ES), and Chronic Restraint Stress (CRS)-utilizing a total of 540 mice for LF fitting. A support vector machine algorithm was applied to distinguish each model group based on the two-dimensional distribution of the variables γ and μ in the LF. Statistical analysis was performed using a two-dimensional Kolmogorov-Smirnov test before and after drug administration. We found that the ES model primarily exhibited anxiety-like behaviors, the CRS model predominantly exhibited depression-like behaviors, and the CUMS model displayed both depression-like and anxiety-like behaviors. All three stress models were suitable for LF fitting, with the distribution of CUMS in the γ-μ plane lying between the ES and CRS groups. To assess the therapeutic effect of fluoxetine (FXT) on CUMS, we excluded the CUMS-resistant mice and performed LF analysis. Following FXT treatment, the mice gradually shifted toward the normal area in the γ-μ plane, with a more pronounced shift toward the depression area observed as the modeling time increased. This study identifies a previously unrecognized statistical locomotor pattern in mice with anxiety and depression. By integrating scientific rigor with ethical considerations, this approach also presents a humane paradigm shift in preclinical assessment, accelerating translational breakthroughs in neuroscience research.
Older adults experience high rates of chronic disease that reduce quality of life and independence. In South Texas, these challenges are compounded by limited access to culturally aligned care and a high burden of chronic conditions. Addressing these disparities requires infrastructure that bridges research and practice to support the translation of evidence into real-world care. This manuscript describes the establishment of the Supporting Older Adults through Research Network (SOARNet), a population-specific practice-based research network (PBRN) and reports early lessons from its development and recruitment strategies. SOARNet employs a multi-level leadership structure and an Advisory Board to guide research priorities, review member-initiated proposals, and facilitate collaboration among clinical, research, and community stakeholders. Recruitment strategies included informational materials, clinic visits, and targeted email outreach. Since inception, SOARNet has enrolled 61 members representing healthcare clinicians (55.7%), researchers (18.0%), community members (32.8%), and organizations (8.2%), with targeted email outreach proving most effective (n = 56). SOARNet has supported a collaborative research study, facilitated member consultations, and contributed to dissemination activities. These findings demonstrate the value of population-specific PBRNs in advancing community-engaged translational research to improve care for older adults. Future priorities focus on expanding partnerships and strengthening culturally responsive, bidirectional research.
Mucin-type O-glycosylation (O-GalNAcylation) is a structurally diverse post-translational modification (PTM) that serves as a critical molecular interface at the cell surface. Unlike well-characterized PTMs such as phosphorylation or N-glycosylation, the specific roles of O-GalNAcylation in the mammalian brain have long remained poorly understood. Recent studies have begun to reposition this modification as an important regulator of brain architecture and homeostasis. Emerging evidence suggests that it contributes to neuronal organization, neurovascular integrity, synaptic function, and stress-related behavioral phenotypes, and that its dysregulation may be associated with neurological and psychiatric phenotypes. This perspective synthesizes recent advances to highlight the potential importance of a "brain O-glycan code" in brain health and disease. We discuss how remodeling of this glycan landscape may intersect with aging, neuroinflammation, and synaptic plasticity, and propose that glyco-neurobiology provides an additional conceptual layer for understanding brain vulnerability and resilience. Finally, we consider how targeting O-glycosylation pathways may open new avenues for diagnostic and therapeutic strategies in neurodegenerative and psychiatric disease.
Peritoneal dialysis is a widely used treatment for kidney failure; however, peritoneal dialysis-related infections (exit-site, tunnel infection, peritonitis) occur frequently. The effect of standardised nurse and patient training on peritoneal dialysis infections is uncertain. The aim of this study was to determine whether implementing an international guideline-based standardised training curriculum for nurse trainers and new peritoneal dialysis patients reduces the risk of peritoneal dialysis-related infections compared with existing local training practices. Targeted Education ApproaCH to improve Peritoneal Dialysis (TEACH-PD) was a pragmatic, investigator-initiated, cluster-randomised controlled trial conducted in Australia and New Zealand. Adult patients 18 years of age or older with kidney failure who required training for incident peritoneal dialysis treatment and who were able to provide written informed consent were eligible. Clusters were randomised 1:1 to either the standardised training curriculum or usual care. Participant data and infection outcomes were routinely collected in national patient registries. The primary outcome was time to first peritoneal dialysis-related infection (exit site infection, tunnel infection, or peritonitis). Secondary outcomes were the first of each individual infection type in the primary composite outcome, catheter removal, haemodialysis transfer, all-cause death and quality of life. This trial was registered with ClinicalTrials.gov, number NCT03816111. Between 22 July 2019 and 29 September 2023, 42 clusters were randomised: 21 to the standardised training group and 21 to the usual care group. Overall, 1462 incident peritoneal dialysis patients were included; 667 were assigned to the standardised training group and 795 to the usual care group. A peritoneal dialysis-related infection occurred in 296 of 667 patients in the standardised training group and 297 of 795 patients in the usual care group (sub-hazard ratio 1.230, 95% confidence interval [CI] 1.004-1.507, p = 0.0457). Secondary outcomes were similar in the two groups. Among patients commencing peritoneal dialysis, the use of a standardised training curriculum for nurses and patients based on the International Society for Peritoneal Dialysis guidelines increased peritoneal dialysis-related infection. Implementation-focused research is needed to identify which elements of training require standardisation and where individualisation is most beneficial to support safe, sustainable and patient-centred peritoneal dialysis care. The TEACH-PD trial is funded by MRFF Clinical Trials Activity: Rare Cancers, Rare Diseases and Unmet Need Grant Opportunity; National Health & Medical Research Council BEAT-CKD Program Grant; Health Research Council of New Zealand grant; Metro South Health Research Support Scheme Research Fund-Health System and Health Economics Project Grant; Queensland Health; South Western Sydney Research Small Grant Scheme; International Society for Peritoneal Dialysis; Translational Research Institute Australia; Amgen and Baxter Healthcare (Vantive).
Alcohol use disorder (AUD) is frequently complicated by co-occurring major depressive disorder (MDD), a comorbidity associated with greater clinical severity, elevated relapse risk, and poorer treatment outcomes than either condition alone. Despite the prevalence and burden of this dual diagnosis, interventions that simultaneously address alcohol use and depressive symptoms show limited effectiveness. Converging evidence from neuroimaging and translational research indicates that AUD and MDD share disruptions across large-scale brain networks involved in salience processing, attentional control, and affect regulation. In this Mini Review, we synthesize the literature on transcranial magnetic stimulation (TMS) in AUD, highlighting dominant region-centric paradigms (including those adapted from major depressive disorder), methodological heterogeneity, and ongoing uncertainties regarding optimal targets and mechanisms of action. We then outline a network-based framework centered on the ventral attention network (VAN) as an alternative neuromodulation approach for AUD with co-occurring MDD. Drawing on attention neuroscience and systems-level models of addiction, we emphasize the temporoparietal junction as a theoretically grounded and neuromodulation-accessible entry point for probing VAN responsivity and plasticity. By reframing TMS as a mechanistic probe of network dynamics rather than solely as a therapeutic intervention, this perspective provides a foundation for developing more precise, biologically grounded approaches to addressing heterogeneity and relapse vulnerability in this clinically complex population.
Schizophrenia spectrum disorders (SSDs) are clinically and biologically heterogeneous and lack reliable biomarkers for stratification, treatment response and course prediction. Evidence from postmortem, fluid biomarker, and neuroimaging studies suggests that changes in the blood-brain barrier (BBB) may contribute to pathophysiology in a biologically defined subgroup. However, findings in this context are inconsistent and often based on cross-sectional or indirect measures. This study is a longitudinal, multimodal investigation designed to quantify BBB permeability across disease phases using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and to integrate these measures with deep clinical phenotyping. We recruit inpatients with SSDs and healthy controls (HC). Participants undergo multimodal MRI including DCE-MRI at three time points: acute psychosis (baseline; V1), early treatment (4-6 weeks; V2), and long-term follow-up (2.5 years; V3). Clinical characterization includes standardized measures of psychopathology, functioning and cognition. Blood samples are collected at each visit, while CSF is obtained at V1. DCE-MRI-derived voxel-wise permeability metrics are then analyzed. Primary objectives are to compare BBB leakage cross-sectionally between SSD and HC. Secondary objectives include (i) characterizing spatial and temporal leakage profiles across illness phases, (ii) analyzing associations with psychopathology and biological (e.g., inflammatory) signatures, as well as exploratory identification of subgroups. By providing a longitudinal, BBB-specific neuroimaging framework embedded in a deep phenotyping infrastructure, the IMPACT study aims to elucidate BBB alterations in SSDs and to support stratification approaches in precision psychiatry.
Schizophrenia is a chronic and disabling neuropsychiatric disorder traditionally defined by psychotic and cognitive symptoms. Increasing evidence suggests that neuroinflammatory mechanisms contribute to its pathophysiology and may also underlie common but underrecognized somatic manifestations. These include altered pain perception, characterized by both diminished sensitivity and chronic pain, with important implications for functional outcomes and rehabilitation. This narrative review examines clinical, preclinical, and translational studies addressing the role of neuroinflammation in schizophrenia, with a specific focus on microglial and astrocytic activation, cytokine signaling, oxidative stress pathways, and their interactions with central pain processing circuits. The review was informed by targeted searches of PubMed, Scopus, Web of Science, and Google Scholar, covering articles published from database inception to January 2026, with emphasis on studies relevant to pain modulation, symptom expression, and neurobiological heterogeneity in schizophrenia. Neuroinflammation represents a biologically plausible link between core schizophrenia pathology and altered pain perception. Recognition of pain as an integrated component of disease biology, rather than a secondary complaint, may improve clinical assessment and treatment planning. Investigating and targeting neuroinflammatory pathways holds promise for personalized interventions that address neuropsychiatric symptoms and pain, potentially enhancing rehabilitation outcomes and quality of life. Schizophrenia is a long-term mental health condition that is usually known for symptoms such as changes in thinking, perception, emotions, and memory. However, people with schizophrenia may also experience physical problems that receive less attention, including unusual pain responses. Some may seem less sensitive to pain, while others may live with ongoing pain that affects daily functioning and recovery.This review explores whether inflammation in the brain and body may help explain this pattern. Inflammation is part of the body’s defense system, but when it becomes persistent or unbalanced, it may affect how the brain works. Studies suggest that in schizophrenia, inflammatory changes may influence brain cells, chemical signals, stress pathways, and the systems involved in sensing and responding to pain. We reviewed findings from human and animal research on schizophrenia, inflammation, and pain-related processes. The evidence suggests that inflammation may be one of the biological mechanisms linking schizophrenia with altered pain experience. Understanding pain as part of the illness, rather than as a separate or secondary problem, may help clinicians provide better care. It may also support more personalized treatment and rehabilitation strategies. In the future, treatments that target inflammatory pathways may improve both mental health symptoms and pain-related outcomes, leading to better quality of life for people living with schizophrenia.
Fear extinction and its persistence depend on epigenetic modifications, which can be potentiated by histone deacetylase inhibitors (HDACis). Butyrate (NaBu), a short-chain fatty acid and endogenous HDACi, promotes persistent fear extinction in rodent models by increasing histone acetylation in promoter regions of plasticity- and memory-related genes, thereby enhancing their transcription. To test translational relevance in humans, we conducted a six-arm randomized, triple-blind, placebo-controlled intervention study in 180 healthy participants who underwent a 3-day Pavlovian fear conditioning paradigm. Participants ingested a single dose of NaBu or placebo either before or after extinction learning, the duration of which was additionally manipulated by varying the number of learning trials. NaBu facilitated later retrieval of extinction memory after seven days, both when administered before or after extinction learning, but it did not prevent return of fear during a subsequent reinstatement test. Interestingly, NaBu's effects were contingent on robust extinction learning, emerging only when participants had been exposed to a high number of trials. As no side effects were observed with acute administration of the current dose, these findings support investigating NaBu as a potential adjunct for enhancing extinction-based interventions, such as prolonged exposure therapy, in anxiety disorders.
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are widely used in psychiatry for mood and anxiety disorders but remain underexplored in chronic gastrointestinal conditions such as inflammatory bowel disease (IBD) and disorders of gut-brain interaction (DGBI). This review synthesizes emerging evidence on their potential therapeutic role, focusing on shared neurobiological and immunometabolic mechanisms within the bidirectional microbiota-gut-brain axis. We reviewed preclinical and clinical studies investigating SSRIs and SNRIs in IBD and DGBI, emphasizing neuroimmune, enteric, and microbial pathways relevant to disease modulation. SSRIs and SNRIs inhibit serotonin (SERT) and norepinephrine (NET) transporters, increasing central 5-HT and NE signaling across corticolimbic and autonomic networks. These effects enhance neuroplasticity and BDNF activity, reduce microglial activation and proinflammatory cytokines, and partially normalize hypothalamic-pituitary-adrenal (HPA) axis reactivity. Peripherally, epithelial, and enteric SERT blockade elevates luminal 5-HT, activating 5-HT<inf>3</inf> and 5-HT<inf>4</inf> receptors that promote motility, secretion, and sensory modulation. Both classes also enhance vagal antiinflammatory tone and tighten epithelial barrier integrity by suppressing nuclear factor kappa (NF-κB) signaling and increasing interleukin 10 (IL-10). Through integrated central, enteric, and immune actions, SSRIs and SNRIs can influence mood, pain perception, gut motility, and mucosal inflammation, key determinants of symptom burden in IBD and DGBI. SSRIs and SNRIs hold promise as multimodal modulators of the microbiota-gut-brain axis, bridging psychiatric and gastroenterological care. However, mechanistic preclinical studies and rigorously designed, adequately powered randomized trials are needed to define causal pathways, optimal dosing, and patient stratification strategies.
Memory impairment is a common comorbidity in temporal lobe epilepsy (TLE) and is thought to arise from hippocampal dysfunction and disrupted interactions within a distributed memory network involving medial temporal, frontal, and parietal cortical regions. However, the network-level mechanisms underlying memory impairment in TLE remain poorly understood. Leveraging complementary intracranial electroencephalography (iEEG) and resting-state functional magnetic resonance imaging (rsfMRI), this study aimed to investigate hippocampal network alterations associated with memory dysfunction in TLE and characterize hippocampal-cortical connectivity patterns linked to individual differences in memory performance. This retrospective study included 29 patients with TLE who underwent structural MRI and rsfMRI, 13 of whom also underwent interictal iEEG. For each participant, 94 subject-specific regions of interest (ROIs) were generated, including 92 cortical ROIs from individualized rsfMRI parcellation and bilateral hippocampal ROIs defined using FreeSurfer subcortical segmentation. iEEG signals were projected onto these ROIs for cross-modal alignment. Hippocampal-cortical connectivity was estimated using rsfMRI functional connectivity and iEEG imaginary coherence, with hemispheres standardized relative to the epileptogenic side. Memory-related connectivity within the hippocampal network was then identified through behavioral-connectivity correlation analysis followed by Elastic Net regularization. Increased ipsilesional hippocampal-cortical alpha-band (8-12 Hz) connectivity derived from interictal iEEG was significantly correlated with worse Logical Memory performance. Consistently, rsfMRI analyses revealed a significant epileptogenic side (ipsilesional vs. contralesional) and connection type (within- vs. between-hemisphere) interaction, with stronger within-hemispheric hippocampal-cortical connectivity in the ipsilesional hemisphere. Behavioral-connectivity analyses indicate that immediate and delayed recall shared a core episodic memory architecture, but delayed recall relied more on large-scale network coordination supporting retrieval after a delay. Our multimodal findings suggest that increased hippocampal connectivity in the epileptogenic hemisphere may reflect pathological hypersynchronization that disrupts efficient memory network coordination in TLE and highlight hippocampal connectivity as a promising candidate biomarker for characterizing individual memory outcomes.
The FDA has the authority to regulate tobacco products, including the implementation of graphic health warnings on cigarette packaging. This study examines the short-term effects of these front-of-package health warnings on smokers' attention, package preferences, and intentions to quit. A total of 951 smokers were recruited via Amazon Mechanical Turk. Participants completed an online survey that included demographic questions, measures of attention to warnings, package choice, and quit intention. Participants were randomly assigned to view cigarette packs with or without warnings. First, exposure to warnings increased attention to the warning area (OR = 1.747, p = 0.0109), and increased the likelihood of choosing packages without warnings as prices increased (OR = 18.244, p<0.001). Additionally, focusing on the warning content also made smokers more likely to choose packages without warnings as price increased (OR = 5.025, p<0.001). However, warnings had no significant effect on quit intentions. Warnings effectively capture attention and influence cigarette package preferences, but their impact on quit intentions was not detectable after single exposure. These findings suggest that while warnings may affect short-term purchasing behavior, they are insufficient for driving cessation. Future research should investigate the long-term impact of warnings and consider other factors influencing quitting behavior.
Lewy body diseases (LBD) collectively share α-synuclein Lewy pathology, yet present wide clinical heterogeneity, with overlapping motor and non-motor features and progression patterns that challenge traditional diagnostic boundaries. To resolve this spatiotemporal heterogeneity at the biological level, we applied a data-driven atrophy progression framework to MRI data from 833 individuals across Parkinson's disease, dementia with Lewy bodies, and prodromal isolated REM sleep behaviour disorder using the Subtype and Stage Inference algorithm. Four transdiagnostic subtypes (A: Early cortico-limbic/late basal ganglia, B: Early basal ganglia/late limbic, C: Early temporo-limbic/late basal ganglia, and D: Early basal ganglia-cingulate/late cortex) emerged, each defined by a distinct spatiotemporal progression of atrophy that explained cognitive, motor, and psychiatric variability. An early cortico-limbic/late basal ganglia subtype represented a dementia-prone subtype across clinical diagnoses, with limbic involvement associating with the emergence of visual hallucinations. These biologically relevant spatiotemporal atrophy subtypes provide an interpretable stratification of patients with LBD, with the potential to refine prognosis, improve clinical trial stratification, and guide precision therapeutic approaches. This work was made possible by an Ignition grant from the University of Sydney and University College London (Global Engagement Fund).
The assessment of activity in adult-onset Still's disease (AOSD) remains difficult because of no validated score for this disease. A task force commissioned by the European Alliance of Associations for Rheumatology (EULAR) undertook a 3-round consensus-building study to elicit items to be included in the criteria for the assessment of disease activity for AOSD. Candidate items were initially extracted from a systematic literature review, and additional items were collected from expert physicians' answers to open-ended questions during the first Delphi round via a web-based application. In the second round, the expert physicians scored items for relevance. Subsequently, the expert physicians were presented the results of the group ratings and asked to score again in the third and final Delphi round. The cutoff for including an item in the criteria for the assessment of disease activity was set at ≥75% for the top 2 ratings ('absolutely required' and 'important'). In total, 25 expert physicians from 7 countries participated in all 3 Delphi rounds. A total of 28 candidate items were initially identified. In the final expert rating, the 14 following items were above the cutoff: fever, cutaneous rash, arthralgia, arthritis, splenomegaly, lymphadenopathies, pleuritis, pericarditis, white blood cell count ≥10,000/mm3, polymorphonuclear cells ≥80% of white blood cell count, increased erythrocyte sedimentation rate, increased serum C-reactive protein level, increased serum ferritin level, and elevated liver enzyme levels. The study is the first part of the development and validation of the criteria for the assessment of disease activity in AOSD.
Optical coherence tomography (OCT) quantifies retinal neuroaxonal loss related to neurodegeneration in people with multiple sclerosis (pwMS) and is associated with physical and cognitive disability. However, no data exist on the relationship between OCT metrics and cognitive progression independent of relapse activity (cognitive PIRA). To assess if OCT can prognosticate cognitive PIRA events in pwMS. Prospective study with baseline OCT (peripapillary retinal nerve fiber- (pRNFL), macular ganglion cell-inner plexiform- (mGCIPL) and inner nuclear layers (mINL)) and brief international cognitive assessment for MS (BICAMS) at yearly visits. Cognitive PIRA in each test was defined as more than 10% decrease compared to previous visit (reference) and confirmed 12 months later (confirmation visit), without relapses 90 days before or 30 days after the event and confirmation visits. We employed Cox regression models adjusting for age, baseline cognitive test, education, and treatment. 98 pwMS followed for a median of 5 years (63% female, 81% relapsing-remitting, age: 50.5 ± 11.6 years, median EDSS: 3.0). Each 1 µm increase in pRNFL thickness was associated with a 6% lower risk of Symbol Digit Modalities Test (SDMT) PIRA events (Hazard ratio (HR) = 0.94, p = 0.027). Each 1 µm increase in mGCIPL thickness was associated with a 6% lower risk of Verbal Learning and Memory Test (VLMT) PIRA (HR = 0.94, p = 0.040). Each 1 μm increase in mINL thickness was associated with 20% lower risk of VLMT-PIRA (HR = 0.80, p = 0.030) and 50% higher risk of SDMT-PIRA events (HR = 1.50, p = 0.049). Retinal layers can be sensitive, patient-friendly prognostic markers of cognitive PIRA in pwMS.