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Premature closure underlies bias in medical diagnosis in students: A randomised controlled experiment.

OBJECTIVE: The purpose of the study reported in this article was to shed light on the cognitive mechanism mediating between biasing information and diagnostic error. The literature suggests at least two different hypotheses: premature closure leading biased participants to spend less time on diagnosis or increased competition between diagnostic hypotheses. The latter hypothesis predicts that biased participants would spend more time reaching a diagnosis. METHOD: Using the salient distracting findings (SDF) experimental paradigm, we biased 58 fourth-year medical students while diagnosing 12 clinical vignettes in a within-group incomplete block design under three conditions: cases presented without SDF, with SDF at the beginning and with SDF at the end. For each of these conditions, diagnostic accuracy, the number of SDF-related mistakes and time per word needed to process the case were recorded. The data were analysed using linear mixed modelling. Estimated marginal mean scores were reported. RESULTS: Participants confronted with salient distracting features (SDFs) at the beginning of a clinical case demonstrated significantly lower diagnostic accuracy (mean 0.11) compared with the No-SDF condition (0.27), representing a 61% reduction (F2,693&#x2009;=&#x2009;11.995, p&#x2009;<&#x2009;0.001), and made more SDF-related mistakes (F2, 693&#x2009;=&#x2009;16.395, p&#x2009;<&#x2009;0.001). When SDFs were presented at the end of the case, diagnostic accuracy was also reduced (mean 0.17; 36% reduction), but processing time did not differ from the No-SDF condition. Only early presentation of SDFs was associated with reduced processing time per word (F2,636&#x2009;=&#x2009;4.799, p&#x2009;<&#x2009;0.01), consistent with premature closure. CONCLUSION: These findings demonstrate that biasing information increases diagnostic error in medical students and that only early bias is associated with reduced information processing. The data do not support the competition hypothesis for early bias, as processing time did not increase under biasing conditions. Premature closure can therefore be directly observed rather than inferred, inviting further research.

Humans

Factors associated with successful integration of pharmacists into residential aged care teams: A qualitative study.

BACKGROUND: Australia's Aged Care Onsite Pharmacist program aims to support quality use of medicines in residential aged care homes. This is a novel role introduced into existing teams in a complex environment. Factors associated with successful integration since implementation are currently unknown. AIM: This study aims to explore the perspectives of pharmacists and other stakeholders within aged care homes regarding successful integration of the novel aged care pharmacist service into healthcare teams. METHODS: A qualitative approach, using interpretive descriptive methodology, was used to explore perspectives. Semi-structured focus groups and interviews with pharmacists, nursing and care staff, allied health professionals, general practitioners, residents, and family members were undertaken. Data were collected via Zoom&#x2122;, audio- and video-recorded, and transcribed verbatim. Two researchers undertook inductive thematic analysis to identify key themes. RESULTS: 30 participants across focus groups, focus-group interviews, interviews, and member-checking processes contributed. An overarching theme of proactivity and showing a genuine interest in others underpinned three key themes. Theme 1: Pharmacists needed to be seen, through physical presence and availability, as well as developing a distinct identity. Theme 2: Pharmacists needed to build trust, through collaboration in real time and demonstrating value. Theme 3: Pharmacists needed to develop an understanding of the aged care home environment, including social and contextual norms, as well as procedures, routines and roles. DISCUSSION: This research complements existing understandings of interprofessional collaboration and teamwork amongst healthcare professionals. Themes were interlinked; we used a sensitising framework, social cognitive theory, to present and explain the findings and interactions that can support pharmacist integration into existing teams. Aged care services should structure onboarding to prioritise early visibility, clarify roles and organisational needs, and foster in-person collaboration. Pharmacists should demonstrate proactivity and an authentic interest in all staff, residents and families.

Humans

Multicenter randomized effectiveness/implementation trial of a digital self-management support tool to improve the quality of life during adjuvant hormonal therapy for patients with early breast cancer: The HOPE trial.

BACKGROUND: For patients with hormone receptor (HR) positive early breast cancer (BC), adjuvant endocrine therapy (ET) represents the cornerstone of treatment. However, 75% of patients experience ET-related symptoms that negatively affect their quality of life (QOL). Despite their high prevalence, these symptoms are often underestimated and under-addressed during consultations. As a result, non-adherence to ET is common and remains a major barrier for optimal disease and survival outcomes. METHODS: National, prospective, randomized, open-label hybrid type 1 effectiveness/implementation trial conducted in France comparing a personalized digital health pathway plus standard of care (SoC) vs. SoC alone in patients with HR+ early BC reporting ET-related symptoms. 180 patients will be randomized 1:1 to receive either 12&#xa0;weeks of the digital health pathway or 12&#xa0;weeks of SoC. The intervention is anchored by the Resilience&#xa9; digital companion including remote symptom and needs assessment, an introductory nurse-navigator phone call, and access to personalized, symptom-specific online educational and self-management programs (physical activity, yoga, meditation or cognitive behavioral therapy). In both arms, patients will be invited to wear a wearable device to objectively monitor behavioral parameters. The primary endpoint is the ET symptoms scale of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-BR45 over 12-weeks. Secondary endpoints include other QOL domains, self-reported ET adherence, eHealth literacy, self-efficacy, and evaluation of the implementation process. DISCUSSION: This study should provide evidence on the effectiveness and real-world implementation of a personalized digital health pathway to improve QOL in patients experiencing ET-related symptoms. TRIAL REGISTRATION: ClinicalTrials.gov NCT06781996; Protocol version 3.0.

Humans

Pregnancy diet based on ancestral patterns increases growth in subcortical fetal brain regions.

Evidence on the biological basis for maternal nutrition effects on fetal and newborn neurodevelopment remains limited. This randomized controlled trial in Ecuador tested a maternal dietary pattern-derived from empirical studies of nutrition in human evolution and adapted locally-on offspring growth and brain development. Pregnant women (n = 215) in their first trimester were randomized to: 1) control (n = 104); or 2) Mikhuna ("nourish" in Kichwa) intervention (n = 111). The intervention, from 12 wk gestation to birth, consisted of a weekly food delivery (8 eggs, 500 g fish, and a variety of sustainably sourced fruits and vegetables) and a behavior change communication strategy encouraging diet diversity and limiting highly processed foods. Longitudinal data collection occurred at 12 wk, 21 wk, 35 wk gestation, and 2 wk postpartum, and included ultrasound imaging of fetal bone and brain parameters, maternal dietary intakes, anthropometry, socioeconomic and demographic variables, and other biomarkers. At close of intervention, a significantly higher percentage of women met the minimum dietary diversity threshold in Mikhuna (74.5%) vs. control groups (55.8%) (P = 0.004). Generalized linear regression models showed significant differences in Mikhuna compared to control for: corpus callosum length 0.19 cm (95% CI [0.02, 0.35]), gangliothalamic ovoid height 0.15 cm (95% CI [0.03 to 0.26]), and femur length -0.10 cm (95% CI [-0.19, -0.02]) from 21 wk to 35 wk; and corpus callosum Z 0.56 (95% CI [0.03, 1.09]) and femur length Z -0.21 (95% CI [-0.42, 0.00]) at 35 wk. The Mikhuna intervention increased the growth of subcortical fetal brain structures, which have established roles in motor control, cognition, and signal transmission.

Female

Use of Wearable Sensors in Angelman Syndrome: A Systematic Review.

BACKGROUND: Wearable sensors are a promising method for collecting clinical trial outcome data for people with Angelman syndrome (AS). However, there has yet to be a systematic probe into the ways in which wearable sensors have been successfully used in AS. The current study aims to provide a quantitative summary of wearable sensors used in AS, including contexts of use and psychometric properties, and to present key narrative highlights. METHOD: Literature searches were performed in three electronic databases: APA PsycInfo, PubMed and Web of Science Core Collection. Data items were categorized into four categories: sample characteristics, study methodological details, wearable sensor characteristics and psychometric properties assessed. Sample characteristics included sample size, age, biological sex, race/ethnicity and cognitive/developmental functioning. Study methodological details were subdivided into study design and setting. Wearable sensor characteristics included sensor type, placement site, means of attachment, assessed construct and sensor-related data loss. Psychometric properties assessed included reliability and validity of sensor-derived data. RESULTS: We identified 16 articles through our systematic review. Wearable sensors were used to study sleep (n&#x2009;=&#x2009;10, 62.5%), language (n&#x2009;=&#x2009;2, 12.5%), gait (n&#x2009;=&#x2009;2, 12.5%), caregiver proximity (n&#x2009;=&#x2009;1, 6.3%), EEG power (n = 1, 6.3%),&#xa0;and arousal (n&#x2009;=&#x2009;1, 6.3%) in AS through actigraphs, vocalization recorders, inertial sensors, radio-frequency identification watches, wireless EEG caps,&#xa0;and functional near-infrared spectroscopy caps, respectively. Findings from these studies broadly indicate that wearable sensors are feasible, reliable and valid for assessing a range of behaviours relevant to AS. CONCLUSIONS: Wearable sensors are a promising solution to enhance assessments in AS. However, with the small extant literature characterized by small sample sizes and restricted focus on a few relevant features in AS, there remains ample opportunities to explore the use of wearable sensors in people with AS. Additional studies will better inform clinical decision-making and ultimately improve the lives of people with AS and their families.

Humans

Systematic Review of Symptoms of Catatonia in Autism Spectrum Disorder.

Catatonia is a complex neuropsychiatric syndrome characterized by disturbances in mood, motor function, behavior and speech. It is increasingly recognized in individuals with autism spectrum disorder (ASD), although its identification remains challenging due to the overlapping clinical features of the two conditions. Shared characteristics, such as echophenomena, mannerisms, social indifference and repetitive behaviors can obscure accurate diagnosis. Although reports suggest a significant prevalence of catatonia among individuals with ASD, the condition remains poorly understood and frequently under recognized, leading to substantial diagnostic and treatment challenges. A systematic review was conducted to characterize the symptoms of catatonia in individuals with ASD. The literature search included peer-reviewed journal articles published in English from 1980 onward, focusing on studies examining co-occurring catatonia and ASD. A qualitative framework analysis was implemented to evaluate 45 peer-reviewed studies, with findings interpreted in relation to, and extending beyond, the diagnostic criteria for catatonia outlined in the International Classification of Diseases, 11th revision (ICD-11). The objective was to identify symptom patterns extending beyond current diagnostic frameworks and to support improved clinical recognition and diagnostic precision in ASD populations. The review identified six primary symptom clusters associated with catatonia in individuals with ASD: (1) psychomotor activity, (2) speech disturbances, (3) changes in behavior/skills/functions, (4) mental health symptoms, (5) physiological symptoms, and (6) symptoms related to arousal and awareness. Notably, several symptoms observed within these clusters are not currently included in the ICD-11 diagnostic criteria for catatonia. These additional symptoms include tics, motor compliance, incoherent speech, self-injury, impaired cognition, and appetite changes, suggesting a broader clinical presentation of catatonia in ASD populations than is presently captured in existing diagnostic frameworks. The findings of this review highlight the significance of enhancing clinicians' awareness and understanding of how catatonia manifests in individuals with ASD. Most notably, six symptom clusters, psychomotor changes, speech disturbances, behavioral and functional regression, affective and psychiatric symptoms, physiological symptoms, and arousal/awareness disturbances, were observed. Several symptoms identified in this review are not included in the current diagnostic criteria, and their recognition may facilitate in earlier identification and timely intervention, potentially preventing the severe consequences of untreated catatonia in this population.

Humans

From prediction to mechanism: Explainable AI uncovers plasma and CSF proteomic signatures of Alzheimer's disease.

Alzheimer's disease (AD) plasma and cerebrospinal fluid (CSF) proteomics can distinguish AD from cognitively normal controls, but the generalizability of machine learning performance and the recurrence of biological signals across datasets require cautious interpretation. We developed an explainable artificial intelligence framework spanning two fluids and four ADNI proteomic datasets, covering 2082 modality specific samples, all analysed internally within ADNI. Phase 1 analysed plasma using a 119 analyte NULISA and targeted UPENN panel (n&#xa0;=&#xa0;727; 216&#xa0;CE, 511 controls). Phase 2 extended the analysis to CSF using SOMAscan7k, TMT-MS and targeted SET2, with Elecsys A&#x3b2;42, A&#x3b2;40, total tau and p-tau181 as anchor biomarkers. Only SOMAscan was subject-independent relative to Phase 1 plasma; TMT-MS and SET2 overlapped with Phase 1 for 96.0% and 97.7% of subjects and therefore are not independent replication cohorts. Under subject-level splits with fold internal preprocessing, we compared Elastic Net, Explainable Boosting Machines and gradient boosted trees with SHAP-based explanations. Among the candidate pipelines, we selected the pipeline with the highest held-out test ROC AUC for each platform; the selected values were 0.927 in plasma and 0.954-0.973 across the three CSF datasets. Because the same held out test performance was used for pipeline selection and headline reporting, these are optimistically selected single-holdout estimates, not unbiased estimates of generalizable or clinical performance. Explanations identified five recurring biological axes within ADNI: cholinergic (ACHE), tau/14-3-3 (YWHAG, YWHAZ, YWHAB, YWHAE), neuro-axonal (NEFL, NEFH), microglial/complement (CHIT1, SMOC1, CHI3L1, C7, CFH) and synaptic (NPTXR, NPTX2, DLG4, SYT5, VSNL1, ELAVL2). CSF analyses showed synaptic vesicle-cycle enrichment (q&#xa0;=&#xa0;2&#xa0;&#xd7;&#xa0;10-6), and CSF YWHAG correlated strongly with total tau (&#x3c1;&#xa0;=&#xa0;0.87). Cross-fluid directional concordance was modest overall (54-57%) but increased to 73-80% among mapped analyte/protein rows reaching q&#xa0;<&#xa0;0.05 in CSF. These findings provide hypothesis-generating, internally supported evidence within ADNI. Independent external cohorts with locked pipelines are required to evaluate generalizable performance and biological reproducibility; the overlapping TMT-MS and SET2 analyses should not be interpreted as independent replication.

Alzheimer Disease

Context-dependent functional diversity of dorsomedial posterior parietal neurons revealed by single-unit fMRI mapping during naturalistic viewing.

The dorsomedial posterior parietal cortex (dmPPC) plays an important role in episodic processing by integrating sensory, cognitive, and motor information across distributed brain systems. However, how individual dmPPC neurons participate in large-scale functional organization during naturalistic experience remains poorly understood. To address this question, we combined single-unit electrophysiology and awake fMRI in five rhesus macaques of both sexes viewing identical naturalistic video stimuli. Using single-unit fMRI mapping, we generated whole-brain neuron-BOLD functional maps by correlating individual neuronal activity with voxel-wise fMRI signals across the brain. We found that neuron-BOLD functional maps exhibited strong context-dependent organization, with neurons recorded during the same video context showing substantially greater similarity than neurons recorded during different video conditions. Compared with neuronal spiking activity or critical fMRI frames alone, neuron-BOLD functional maps more robustly captured contextual structure. Despite this shared large-scale organization, a substantial subset of neighboring neurons recorded simultaneously from the same electrode displayed markedly distinct whole-brain association patterns, revealing substantial local functional heterogeneity within the dmPPC. This local heterogeneity was not readily explained by waveform-based putative cell class or by opposing neuronal firing dynamics. In addition, distributed cortical and medial temporal regions exhibited highly context-dependent neuron-BOLD association patterns during naturalistic viewing. Together, these findings demonstrate that dmPPC neurons participate in dynamic and heterogeneous large-scale functional organization during naturalistic episodic processing. More broadly, this study establishes single-unit fMRI mapping as a framework for linking single-neuron activity to distributed whole-brain dynamics across contextual conditions.Significance Statement Using single-unit fMRI mapping, this study examined how individual dorsomedial posterior parietal cortex (dmPPC) neurons relate to large-scale brain activity during naturalistic video viewing in macaque monkeys. We found that neuron-BOLD functional maps exhibit strong context-dependent organization and capture contextual structure more robustly than neuronal spiking activity or fMRI frames alone. Despite this shared organization, a substantial subset of neighboring dmPPC neurons displayed markedly distinct whole-brain association patterns, revealing local functional heterogeneity that was not readily explained by waveform-based putative cell class or opposing firing dynamics. These findings provide insight into how local neuronal populations participate in distributed brain-wide functional organization during naturalistic episodic processing.

Journal Article

Multi-centre randomised controlled feasibility trial with embedded process evaluation of a samba percussion intervention for people living with Parkinson's disease: a protocol for the Sparky Samba trial.

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder, its principal symptom being deterioration of motor function. Current treatment options are limited to symptom management but there is evidence that physical activity can provide motor benefits. More recently there is evidence to suggest that rhythmic auditory stimulation may improve gait and balance in PD. Sparky Samba is a community initiative in South Wales, UK, founded by a person living with PD. Sessions incorporate the following samba rhythms from a trained facilitator and are held weekly in a community setting. METHODS: The Sparky Samba trial is a multi-site, non-blinded, randomised controlled feasibility trial of Sparky Samba compared with activity as usual. A total of 60 people with PD will be randomised 1:1 to take part in a local Sparky Samba group for 12 weeks or continue their normal activities for the same length of time. The primary outcome is feasibility defined by recruitment, retention, data completeness and intervention adherence. Secondary outcomes relating to motor function, cognition, well-being and self-efficacy will also be assessed at baseline and at 12 weeks. Additionally, we will conduct a process evaluation to understand contextual mechanisms surrounding Sparky Samba. This will be achieved through qualitative interviews and structured participant questionnaires following individual trial completion and through structured questionnaires with intervention delivery staff, supplemented with qualitative interviews. ANALYSIS: Feasibility outcomes will be assessed according to pre-defined criteria. For secondary outcomes, means and standard deviations (or medians and IQRs) will be calculated by arm, alongside 95% CIs for change from baseline to 12-week follow-up. Qualitative data will be subject to thematic analysis using NVivo software. ETHICS AND DISSEMINATION: This study received a favourable ethical opinion from the North of Scotland Research Ethics Committee in April 2025 (REC reference 25/NS/0037). Study results will be disseminated through the peer-review literature, the ISRCTN registry and directly to participants, which will be facilitated by the study's public and patient involvement steering group. TRIAL REGISTRATION NUMBER: ISRCTN11861663.

Humans

Epilepsy Is Part of the CNS Phenotype in Classic Infantile Pompe Disease.

BACKGROUND AND OBJECTIVES: Enzyme replacement therapy has not only significantly improved motor outcome and survival in patients with classic infantile Pompe disease, but also revealed previously unrecognized central nervous system (CNS) involvement. In this international study, involving patients from the Netherlands, Italy, Argentina, Germany, the United Kingdom, and Taiwan, we investigated whether epilepsy should be considered part of the CNS phenotype. METHODS: We included patients with classic infantile Pompe disease, defined by the presence of hypertrophic cardiomyopathy, symptom onset < 6 months of age, complete acid &#x3b1;-glucosidase (GAA) deficiency, and/or 2 severe variants in the GAA gene, who developed epilepsy. Data on epilepsy characteristics, electroencephalogram (EEG), cognitive testing, serum neurofilament light chain (NfL), and brain magnetic resonance imaging (MRI) were retrospectively collected. RESULTS: Seventeen patients from 10 centers were identified. The median follow-up duration was 13.7 years (range 3.3-19). Seven patients had deceased at the time of analysis. The median age at first seizure was 11.5 years (range 2.5-17.5). Seizure semiology was variable: six patients experienced generalized tonic-clonic seizures and 3 focal seizures with impaired consciousness only; 6 had multiple seizure types, and 7 experienced seizures during fever or infection. Seizure frequency varied considerably (in 9 occasionally, 5 monthly, 2 weekly, 1 daily). The most common EEG findings were a slowed background activity and focal epileptiform discharges, not substantially activated by sleep. Levetiracetam was most frequently used as antiseizure medication. Overall, 70% of patients became seizure-free. Serum NfL was elevated in all 6 patients in whom it was measured, and 8 of 10 patients had an intelligence quotient &#x2264;66 at onset of epilepsy. Although brain MRI was not always performed at the age of first seizure, 14 of 15 patients showed white matter abnormalities, which were extensive in 11 of 14 (score &#x2265;7/12). Brain atrophy was present in 9 cases and calcifications in 4. DISCUSSION: Our findings suggest a potential increased frequency of seizures in classic infantile Pompe disease in comparison with unaffected children, occurring predominantly after the age of 7, and that epilepsy is part of the CNS phenotype. The risk of seizures should be evaluated during follow-up in long-term survivors with classic infantile Pompe disease.

Journal Article

Toward personalized interventions for preventing depression in primary care: Qualitative and quantitative findings from the e-predictD pilot study.

BACKGROUND: The predictD intervention, delivered by family physicians (FPs), has demonstrated effectiveness and cost-efficiency in preventing depression and anxiety. The e-predictD study aims to design, develop, and evaluate a novel personalized intervention for depression prevention by integrating information and communication technologies (ICTs), risk prediction algorithms, and decision support systems (DSS) for both patients and FPs. OBJECTIVE: To evaluate the satisfaction, usability, and acceptability, of a beta version of the e-predictD intervention in primary care settings. METHODS: The e-predictD intervention follows a biopsychosocial approach, including an initial patient-FP interview, specific FP training, and an app. A &#x3b2;-version was tested in a pilot study without a control group over three months. The app integrates a validated depression risk prediction algorithm, decision algorithms, and a monitoring system supporting the DSS. The DSS generates a personalized prevention plan (PPP) from eight intervention modules: physical exercise, social relationships, problem-solving, communication skills, decision-making, assertiveness, sleep improvement, and cognitive restructuring. Patients and FPs discussed the PPP in a 15-minute baseline interview, selecting modules for implementation over three months. Semi-structured interviews gathered feedback. Assessments included depression (PHQ-9), anxiety (GAD-7), quality of life (SF-12), and major depression risk (predictD algorithm). RESULTS: Six FPs from six Spanish cities enrolled 56 non-depressed patients at moderate-to-high risk of depression; 47 (84%) completed follow-up. The app was used for a median of six days (interquartile range: 1-30). Both FPs and patients expressed satisfaction, leading to incorporated improvements. After three months, significant reductions in major depression risk and anxiety symptoms were observed, alongside improved mental quality of life. However, no significant changes were found in depressive symptoms or physical quality of life. CONCLUSION: This pilot study supports the feasibility and acceptability of the e-predictD &#x3b2;-version, despite lower-than-expected app usability. Health improvements were observed, warranting confirmation in a randomized controlled trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03990792.

Adult

Efficacy and safety of add-on topiramate vs. metformin on cardiometabolic profile in patients of schizophrenia on atypical antipsychotics with metabolic syndrome: an active-controlled, rater-blinded, parallel-design randomized controlled trial.

BACKGROUND: Metabolic syndrome is common among patients with schizophrenia, but current treatment options are limited, with metformin being the most studied. While placebo-controlled studies suggest potential benefits of topiramate, comparative efficacy and safety data are lacking. This study aimed to compare the efficacy and safety of topiramate versus metformin for treating metabolic syndrome and reducing cardiovascular risks among patients with schizophrenia. METHODS: A randomised, open-label, parallel-group clinical trial was conducted on 60 patients of schizophrenia with metabolic syndrome, randomised equally to receive either topiramate (50&#xa0;mg/day) or metformin (1000&#xa0;mg/day) for eight weeks. Primary outcome was cardiovascular risk score (QRISK3), and secondary outcomes were LDL&#x2236;HDL ratio, insulin resistance (HOMA-IR), positive and negative syndrome scale (PANSS), Montreal Cognitive Assessment (MoCA) and clinical global impression-Schizophrenia scale (CGI-SCH) scores. RESULTS: Over the study period, QRISK3 scores improved significantly in both groups [topiramate: MD&#x2009;=&#x2009;0.61 (0.02 to 1.21), p&#x2009;=&#x2009;0.04; metformin: MD&#x2009;=&#x2009;0.45 (0.07 to 0.83), p&#x2009;=&#x2009;0.02], with no significant between-group difference in unadjusted analysis (p&#x2009;=&#x2009;0.648). However, ANCOVA adjusting for baseline QRISK3 revealed a significantly greater improvement in the topiramate group (&#x3b2; = -0.324, p&#x2009;=&#x2009;0.043). Metformin showed significant within-group improvements in LDL: HDL ratio and HOMA-IR; however, ANCOVA adjusting for baseline HOMA-IR showed the between-group difference remained non-significant (&#x3b2; = -1.209, p&#x2009;=&#x2009;0.078). Both groups showed significant improvements in PANSS and CGI-SCH scores, with no significant between-group differences in MoCA scores. A moderate correlation between the QRISK3 change, the PANSS change, and the CGI-SCH-I scores was observed in the topiramate group and the total population. Regression analysis identified PANSS change as a predictor of QRISK3 improvement. CONCLUSION: Topiramate demonstrated comparable, and on adjusted analysis superior, cardiovascular risk reduction compared to metformin, supporting its use as a viable alternative in the management of metabolic syndrome in patients with schizophrenia on atypical antipsychotics, particularly where metformin is contraindicated.

Humans

Gene-environment interaction between perinatal oxytocin exposure and Pten mutation shapes epigenetic reprogramming of oxytocin signaling and behavior in mice.

Synthetic oxytocin (Pitocin) is the most commonly used pharmacologic agent for induction and augmentation of labor. Beyond its uterotonic effects, oxytocin plays a critical role in neurodevelopment and social behavior. Dysregulated oxytocin signaling has been implicated in autism spectrum disorder (ASD), raising concern that perinatal exposure to exogenous oxytocin may have lasting neurodevelopmental consequences. This study aimed to determine whether offspring harboring a genetic predisposition for ASD are differentially impacted by perinatal oxytocin exposures, with a focus on long-term oxytocin signaling and autism-like behavior. Pregnant mice carrying offspring with heterozygous mutations in phosphatase and tensin homolog deleted on chromosome ten (Pten), a well-established monogenic risk factor for ASD, received continuous oxytocin versus phosphate-buffered saline (PBS) control via micro-osmotic pumps during late gestation. Wild-type (WT) offspring exposed to each treatment served as a secondary control. Adult offspring were assessed for oxytocin receptor (Oxtr) methylation in the frontal cortex and hippocampus, oxytocin expression in the hypothalamus, serum oxytocin levels, and were subject to a battery of social and anxiety-related behavior tests. Perinatal oxytocin exposure produced genotype-dependent effects in offspring. Epigenetic analyses revealed bidirectional remodeling of Oxtr methylation in the frontal cortex and hippocampus, with increased exon 1 methylation in WT mice and decreased methylation in Pten-mutant mice, resulting in significant genotype-treatment interactions. Hypothalamic oxytocin expression increased following treatment regardless of genotype, though baseline levels were higher in Pten-mutant mice. Neither oxytocin treatment nor genotype impacted long-term serum oxytocin levels. Behavioral outcomes were modest but context-specific: repetitive behaviors and cognition performance were unchanged, but oxytocin-treated Pten-mutant mice exhibited increased anxiety-like behavior alongside improved social memory. In contrast, oxytocin-treated WT mice showed reduced social novelty preference. Exploratory analyses suggested potential sex-dependent trends. Our findings support a model in which genetic susceptibility shapes the epigenetic encoding of early-life hormonal signals, thereby recalibrating oxytocin system function and downstream behavioral outcomes. Together, these data highlight the context-dependent effects of perinatal oxytocin exposure and argue against uniformly beneficial or detrimental effects, emphasizing the importance of gene-environment interactions in neurodevelopmental trajectories.

Animals

Clinical efficacy and brain mechanism characteristics of guide chi and regulate spirit tuina therapy in the treatment of post-stroke walking dysfunction: A randomized controlled trial based on fNIRS.

BACKGROUND: This study aims to preliminarily evaluate the role of Guide Chi and Regulate Spirit(GCRS) Tuina in enhancing walking function in post-stroke patients with walking dysfunction; secondly, by using functional near-infrared spectroscopy (fNIRS), it investigates the effect of GCRS Tuina on the restoration of brain function in this patient population. METHODS: Participants in the control group received 4-week rehabilitation treatment, while those in the Combined Tuina Group (CTG) additionally received GCRS Tuina therapy for another 4 weeks on this basis. Functional Ambulation Category (FAC), Fugl - Meyer Assessment Scale for Lower Extremity Motor Function (FMA - LE), and Modified Barthel Index (MBI) were evaluated at the baseline and after 4 treatment weeks. A gait and motion analysis system was used to measure step length, stride, walking speed, and step frequency. FNIRS was used to measure the resting-state functional connectivity(FC) strength, as well as the &#x3b2; - value and HbO2 concentration mean during the walking task. RESULTS: A total of 60 participants completed the randomized, and 53 completed the trial and entered the statistical analysis. Compared with the Single Rehabilitation Group(SRG), the CTG group had higher FAC, FMA-LE, and MBI scores after 4 weeks. After the treatment course, the standardized step length, stride, walking speed, and step frequency of the CTG were higher than SRG. At the Region of Interest(ROI) level, the CTG exhibited 13 inter-ROI FC strengths that were higher than SRG, and the differences could survive the FDR correction (PFDR<0.05). Under the walking task, the CTG group had higher &#x3b2; values in 18 channels and higher Oxyhemoglobin(HbO2) concentrations in 19 channels than the SRG (PFDR <0.05). CONCLUSION: GCRS Tuina therapy can significantly improve patients' walking function, enhance lower limb motor ability and daily living ability. It can improve walking efficiency. Tuina can significantly increase the FC and enhance the activation levels and HbO2 concentrations. The stimulation of Tuina may help reconstruct the brain's motor control network, restore impaired motor function, promote the occurrence of neural plasticity, strengthen the neural circuits in the cognitive-motor-sensory cortex to improve walking function. TRIAL REGISTRATION: This study has been registered with the International Traditional Medicine Clinical Trial Registry (ITMCTR2024000654).

Humans

Associations of Illness Perception, Resignation Coping, and Social Support With Self-Regulatory Fatigue in Patients With Type 2 Diabetes: A Cross-Sectional Study.

AIMS: To examine the associations among illness perception, resignation coping, social support, and self-regulatory fatigue (SRF) in patients with Type 2 diabetes mellitus. The study specifically explores whether resignation coping and social support exhibit indirect associations with SRF in the context of illness perception. DESIGN: A cross-sectional study. METHODS: From November 2024 to October 2025, a convenience sample of 302 adult patients with T2DM was recruited from a tertiary general hospital in China. Participants completed validated instruments with established psychometric properties, namely the Brief Illness Perception Questionnaire, the Medical Coping Modes Questionnaire, the Perceived Social Support Scale, and the Self-Regulatory Fatigue Scale. Statistical analyses included Spearman correlation and serial mediation analysis using the PROCESS Macro (Model 6) with bias-corrected bootstrapping. RESULTS: SRF was positively correlated with negative illness perception (r&#x2009;=&#x2009;0.579, p&#x2009;<&#x2009;0.01) and resignation coping (r&#x2009;=&#x2009;0.612, p&#x2009;<&#x2009;0.01), and negatively correlated with social support (r&#x2009;=&#x2009;-0.598, p&#x2009;<&#x2009;0.01). Serial mediation analysis revealed that illness perception was associated with SRF through indirect pathways involving resignation coping and social support. Resignation coping and social support mediated the association between illness perception and self-regulatory fatigue, both individually and sequentially. CONCLUSIONS: Negative illness perception correlates with higher SRF. This observed correlation is additionally linked to indirect pathways involving resignation coping and lower social support. Collectively, these findings highlight a pattern of interrelated cognitive (illness perception), behavioural (resignation coping), and resource (social support) factors that are associated with self-regulatory fatigue in this cross-sectional study. IMPLICATIONS FOR THE PROFESSION: The findings offer a clear, evidence-based framework for nursing practice. They highlight the potential value of integrated assessment and intervention that simultaneously addresses patients' illness beliefs, maladaptive coping strategies, and social support systems, which are associated with lower SRF and better diabetes self-management. REPORTING METHOD: This study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: Patients participated solely as research participants by providing survey data. They were not involved in the study design, implementation, data analysis, interpretation, or manuscript preparation. All patients provided written informed consent prior to questionnaire completion.

Humans

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I.&#xa0;=&#xa0;50-66%) and Alzheimer's dementias(28.0%&#xa0;=&#xa0;95%C.I.&#xa0;=&#xa0;17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I.&#xa0;=&#xa0;17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I.&#xa0;=&#xa0;36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I.&#xa0;=&#xa0;38.3-45.6%), anxiety(32.0%;95%C.I.&#xa0;=&#xa0;26.5-37.6%), MDD&#xa0;+&#xa0;anxiety(24.7%;95%C.I.&#xa0;=&#xa0;17.9-34.3%), and dementia(19.8%;95%C.I.&#xa0;=&#xa0;12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I.&#xa0;=&#xa0;21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I.&#xa0;=&#xa0;12.0-46.0%), MDD in PVI patients (20.0%;95%C.I.&#xa0;=&#xa0;13.0-29.0%); in coronary artery disease: MDD&#xa0;+&#xa0;anxiety(19.8%;95%C.I.&#xa0;=&#xa0;16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I.&#xa0;=&#xa0;0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I.&#xa0;=&#xa0;0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I.&#xa0;=&#xa0;0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans

Nurse-led attribution remodeling training based on the Neuman systems model to enhance resilience, adaptive coping, and attributional style in women newly diagnosed with breast cancer: A randomized controlled trial.

BACKGROUND: Psychological interventions for patients with breast cancer often overlook the critical role of maladaptive attributional style in shaping their adjustment. Therefore, the need for theory-driven, scalable interventions that target cognitive restructuring, particularly during the vulnerable post-diagnosis period, is clear. OBJECTIVE: To evaluate the effectiveness of a nurse-led attribution remodeling training intervention grounded in the Neuman systems model for improving resilience, adaptive coping, and attributional style among women newly diagnosed with breast cancer. DESIGN: A randomized controlled trial. SETTING: A tertiary general hospital. PARTICIPANTS: A total of 130 eligible women newly diagnosed with breast cancer were recruited between March and November 2024. METHODS: A two-arm parallel-group randomized controlled trial was conducted. Participants were randomly assigned to receive either attribution remodeling training plus routine nursing (n&#xa0;=&#xa0;65) or routine nursing only (n&#xa0;=&#xa0;65). The nurse-led attribution remodeling training intervention, delivered via a blended model of in-person sessions and continued support through the WeChat mobile platform, was designed to systematically reshape maladaptive attributions into more adaptive ones. Resilience (primary indicator), coping strategy (i.e., confrontation, avoidance, resignation), and attributional style (secondary indicators) were assessed at baseline and at 1, 3, and 6&#xa0;months post-baseline. A linear mixed model was used to analyze the effects of group, time, and group-by-time interactions. Effect sizes (Cohen's D) were calculated based on the means and standard deviations. RESULTS: At the 6-month follow-up, the intervention group had better outcomes than the control group in terms of resilience (mean difference: 1.49, 95% confidence interval: 0.37, 2.61), confrontation coping (3.35 [2.33, 4.37]), and adaptive attributional style (4.16 [3.87, 4.45]). Avoidance coping showed a small increase (0.82 [0.22, 1.42]), whereas resignation coping decreased (-1.66 [-2.49, -0.83]). Group effects and group-by-time interactions were statistically significant for all outcomes. Effect sizes at 6&#xa0;months ranged from small for resilience (D&#xa0;=&#xa0;0.28) and avoidance coping (D&#xa0;=&#xa0;0.26) to moderate for confrontation coping (D&#xa0;=&#xa0;0.60) and resignation coping reduction (D&#xa0;=&#xa0;-0.51), and large for attributional style (D&#xa0;=&#xa0;0.94). CONCLUSIONS: Attribution remodeling training is a promising and effective theory-based intervention that can enhance psychological adaptation in women newly diagnosed with breast cancer. By strengthening key defense mechanisms, as conceptualized by the Neuman systems model, the program is effective, scalable, and nurse-deliverable for psycho-oncology care, bridging a critical gap in supportive cancer care and empowering nurses as primary psychological support providers. REGISTRATION: ChiCTR2000031827, registered prospectively on April 11, 2020, www.Chictr.or.cn.

Humans

A narrative systematic review of definitions and diagnostic criteria for disordered eating and eating disorders in type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes and disordered eating (T1DE) affects 8-37.1% of adults and is associated with high rates of morbidity and mortality. The absence of a standardised case definition of T1DE and its severity hinders effective screening, diagnosis and treatment. This systematic review aimed to (1) synthesise existing case definitions and diagnostic criteria for T1DE in adults and (2) identify key characteristics to inform consensus for future diagnostic criteria. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies involved adults (&#x2265;18 years) with type 1 diabetes assessing disordered eating; paediatric studies, mixed samples without disaggregated data, non-empirical designs and non-English publications were excluded. PubMed, MEDLINE, EMBASE, CINAHL and PsycINFO were searched up to November 2025 for peer-reviewed studies involving adults with T1DE. Qualitative and quantitative data on definitions, diagnostic criteria and assessment tools were extracted. Study quality was appraised using a modified Graphical Appraisal Tool for Epidemiological studies (GATE) checklist. Due to heterogeneity of data, a narrative synthesis of findings was performed to describe current definitions of T1DE. RESULTS: Sixty-one studies met the inclusion criteria, with a pooled sample of 111,208 participants (76% women) from over 22 countries. T1DE was defined using a heterogeneous array of terms, diagnostic frameworks and assessment tools (29 distinct methods). The Diabetes Eating Problem Survey-Revised (DEPS-R) was the most used questionnaire, but many studies relied on criteria adapted from general eating disorder classifications or generic questionnaires. Approximately three-quarters of the studies assessed insulin omission behaviours, but the operationalisation of the cognitions for insulin omission varied widely. Beyond physiological markers such as HbA1c and BMI, studies explored various diabetes-related and psychological constructs, although often considering diabetes and disordered eating separately rather than as an integrated condition. CONCLUSIONS/INTERPRETATION: This systematic review highlights the lack of a unified, evidence-based definition of T1DE, resulting in inconsistent screening, diagnostic and reporting practices. Establishing clear, consistent, evidence-based diagnostic criteria and screening questionnaires for T1DE is critical to improving early detection and developing targeted interventions. These findings provide a foundation for refining T1DE definitions as a stepping stone to an international consensus definition. STUDY REGISTRATION: PROSPERO registration no. CRD420250223622 FUNDING: King's College London and King's College Hospital through the KMRT KCH Joint Research Committee studentship. This work was also conducted as part of the National Institute for Health Research (NIHR; CS-2017-17-023)-funded STEADY project (Safe management of people with Type 1 diabetes and EAting Disorders studY). NZ's salary was part-funded by the NIHR via the NIHR Clinician Scientist award to MS; JT and KI are part-funded by the NIHR Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. MS was funded through her NIHR Clinician Scientist Fellowship (CS-2017-17-023).

Humans