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Previous research on communicative outcomes in children treated for nonsyndromic craniosynostosis (NSC) has yielded inconsistent findings, with reported prevalence rates of communicative difficulties varying widely. These discrepancies are attributable to small samples, heterogeneous age groups, and reliance on indirect or non-domain-specific outcome measures. There remains a need for systematic, age-specific screening using validated tools to clarify the nature and prevalence of communicative vulnerabilities in this population. The primary aim was to assess guardian-reported communicative abilities in a consecutive cohort of 5-year-old children treated for NSC and compare outcomes with normative data. Secondary aims were to examine whether reported difficulties were predominantly speech-language based or pragmatic, and to explore differences related to NSC subtype and timing of surgery. This cross-sectional study included 157 children treated for NSC at a national craniofacial centre in Sweden. Guardians completed the Children's Communication Checklist-2 (CCC-2) as part of routine 5-year follow-up. General Communication Composite (GCC) scores and subscale profiles were analysed and compared with published normative data. Group differences across synostosis type and surgical timing were examined using parametric and non-parametric statistical methods. Eighty-five percent of children scored within the normative range on the GCC. Fifteen percent scored below the clinical cut-off, a proportion not significantly different from the normative sample. Group-level differences were primarily observed in the domains of speech and language, with significantly lower scores in speech and syntax, while pragmatic difficulties were uncommon. No significant differences were found between craniosynostosis subtypes. Earlier surgery was associated with higher GCC scores in children with metopic NSC only. Most children treated for NSC demonstrate age-appropriate communicative abilities at 5 years of age. However, subtle vulnerabilities in speech and syntax were present in a subset of children. These findings support the use of screening in routine follow-up to identify children who may benefit from further assessment, while suggesting that broad language disorder-like profiles are uncommon in this population. What is already known on this subject Previous studies report highly variable rates of speech and language difficulties in children treated for nonsyndromic craniosynostosis (NSC), ranging from low to markedly elevated prevalence. What this study adds to the existing knowledge In a large consecutive cohort of 5-year-old children treated for NSC, 85% showed age-appropriate communicative abilities as rated by their guardians and did not differ significantly from normative data. Group-level differences were confined to speech- and language domains (speech and syntax), while pragmatic difficulties were uncommon. Earlier surgery was associated with higher communication scores in children with metopic NSC only. What are the potential or actual clinical implications of this study? Routine screening at follow-up is supported to identify speech- and language vulnerabilities in a minority of children treated for NSC. Broad language disorder-like profiles appear uncommon, suggesting that monitoring of speech and syntax may be more clinically relevant than global language screening alone. Most 5‐year‐old children treated for nonsyndromic craniosynostosis had guardian‐reported communication abilities within the normative range, and the proportion scoring below the CCC‐2 clinical cut‐off did not differ significantly from normative data. Communication vulnerabilities were mainly observed in speech and syntax, whereas pragmatic difficulties and broad language disorder–like profiles were uncommon. Systematic communication screening can support routine craniofacial follow‐up by identifying children who require comprehensive speech and language assessment, without subjecting all children to extensive assessment solely on the basis of their craniosynostosis diagnosis.

There is a long-standing international research interest in how substance use and criminality are intertwined. Research on adolescents in substance use treatment has observed high rates of criminality, but little is known in the international literature about how different types of criminality are patterned among patients. The aim of this study was to identify different criminal profiles, in terms of convictions, among adolescents and young adults in Swedish substance use treatment. The sample included all patients aged 13 to 25 who were in contact with Sweden's largest specialized regional provider of substance use treatment for adolescents and young adults, Maria Ungdom (MU) Stockholm, between 2011 and 2021 (n = 29,960). Data on convictions were gathered from the Swedish National Conviction Register and linked to data from patient journals and other Swedish registers. Latent class analysis was used to identify different subgroups based on 12 different offenses. Differences between these sub-groups on socio-demographic and clinical characteristics were also explored. Over 40% of the patients had been convicted between 2011 and 2021, with drug offenses being the most common. The LCA identified six classes based on offenses included in the convictions, including classes defined by single offense types to a class characterized by multiple offenses. The largest class (47.8%) consisted of patients with primarily drug offenses and the smallest class consisted of patients primarily defined by shoplifting (6.47%). Comprising only about 5% of all patients, the class with multiple offenses accounted for 32.8% of all convictions. Classes differed across socio-demographic and clinical variables, where the class with multiple offenses was the most severe. Patients with no convictions scored more favorably on socio-demographic and clinical variables compared to those who had been convicted. A large share of adolescents and young adults in substance use treatment have been convicted for criminal offenses. However, there is profound heterogeneity in this group related to type of offenses as well as to socio-demographic and clinical characteristics. This heterogeneity should be considered in further research and in the provision of treatment.

Early childhood is a known period of rapid cognitive development and vulnerability for altered developmental trajectories leading to clinical diagnoses. This study explored a transdiagnostic approach to neuropsychological evaluations in early childhood to determine concordance between theoretically based quantitatively derived cognitive and standard diagnostic classification based on clinical judgment in a clinical sample of preschool-aged children in hopes of confirming the ability to identify diagnostic cognitive profiles in early childhood. Neuropsychological evaluation results from 467 children (M = 47.61 months, SD = 14.94 months) were categorized into theoretical quantitatively derived cognitive profiles based on a priori defined score parameters. Chi-square analyses were used to compare quantitively defined profiles with clinical diagnostic impressions. Multinomial logistic regression was used to examine the impact of sociodemographic and medical factors. Evaluation results from only 163 participants (34.9%) quantitatively mapped onto one of the a priori defined cognitive profiles. Quantitative cognitive profile results were consistent with clinical diagnostic impressions. Evaluation results from 304 children (65.1%) led to clinical diagnostic impressions but did not map onto a quantitative cognitive profile due to scores just outside of the a priori quantitative definition. No significant impact of sociodemographic or medical variables was observed. It is possible to evaluate and identify different cognitive profiles associated with clinical diagnoses in preschool-aged children. One-third of the sample demonstrated evaluation results consistent with strictly defined quantitative standardized score cognitive profiles. Rigid quantitatively defined profiles underestimate individual variability indicating that a transdiagnostic approach that combines quantitative analysis and clinical expertise is still necessary to support early recognition of clinical diagnoses and intervention needs. Future work is needed to better define flexible transdiagnostic cognitive models, as well as to examine shared mechanisms for intervention to promote neurodevelopment in young children.

IntroductionHomeless youth experience disproportionately high rates of mental disorders, suicidality, and overdose. Understanding their heterogeneous needs is essential for designing integrated care models. This study examined characteristics, help-seeking reasons, and service use among youth accessing ACCESS Open Minds (ACCESS-OM)-Réseau d'intervention de proximité auprès des jeunes de la rue (RIPAJ), a Montréal-based network serving homeless and at-risk youth.MethodsWe analyzed sociodemographic and clinical data, presenting concerns, and services received by youth referred to ACCESS-OM-RIPAJ (2016-2020). Latent class analysis (LCA) identified clusters based on (1) presenting concerns and (2) service use.ResultsA total of 681 referrals were made to ACCESS-OM-RIPAJ. LCA identified 4 distinct help-seeking clusters: (1) a group characterized by severe material deprivation, including homelessness and unmet basic needs, alongside notable social isolation and higher prevalence of psychotic symptoms, who were more often referred to specialized psychiatric services; (2) a group defined by substance misuse with homelessness and financial instability, with fewer co-occurring concerns, requiring coordination across services; (3) a cluster marked by trauma-related experiences, family difficulties, and suicidality, with less clearly defined service use patterns; and (4) a group characterized by emotional distress, occurring alongside financial precarity and risk of homelessness, who were primarily offered psychological interventions.ConclusionThese findings highlight the heterogeneity of needs among homeless and at-risk youth and the importance of integrated, multi-component mental health programs. Improving access to care across the continuum of needs and presentation severities is essential for preventing adverse outcomes and addressing the cyclical relationship between mental health and homelessness. Different needs, different supports: Understanding mental health service use among homeless and at-risk youthYoung people experiencing homelessness or unstable housing are more likely to face mental health challenges, substance use problems, trauma, and difficulties meeting basic needs such as food, income, and shelter. However, not all youth have the same experiences or require the same types of support. Understanding these differences can help services respond more effectively.This study examined 681 referrals to ACCESS Open Minds-RIPAJ, a network of community and healthcare organizations in Montréal that supports homeless and at-risk youth. We explored the reasons youth sought help and the types of services they received.We found four main groups of youth with different combinations of needs. One group experienced severe homelessness, social isolation, and serious mental health difficulties, including symptoms associated with psychosis. These youth often required specialized psychiatric care. A second group was mainly affected by substance use, homelessness, and financial instability and often needed support from several services working together. A third group was characterized by experiences of trauma, family conflict, and suicidal thoughts, and showed a more dispersed service use. A fourth group mainly experienced anxiety, depression, stress, and unstable housing and was most likely to receive psychological support.Overall, young people who faced the most severe social and housing difficulties also tended to have the most serious mental health problems and required more intensive services. The findings show that homeless and at-risk youth are not a single, uniform group. Their needs vary considerably and require flexible, coordinated responses.Programs that combine mental health care with housing, social, and community supports may be better able to meet the diverse needs of these youth and help prevent the long-term cycle between homelessness and poor mental health.

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. A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. Eligible studies involved adults (≥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. 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. 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. 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).

Background Grand rounds remain an important educational forum within academic medical centres and a longstanding component of postgraduate medical education. At the study centre, the weekly neurology grand round represented the principal recurring organised teaching session available to neurology trainees. Its educational value has not previously been formally explored from the perspective of trainees. Educational commentaries have raised concerns regarding increasing reliance on didactic teaching formats and the impact of public questioning on psychological safety and learning. This study therefore aimed to explore neurology trainees' perceptions of the educational value of the grand round, identify factors influencing its educational value, and examine whether these perceptions varied according to trainee seniority. Methods A qualitative study using semi-structured focus groups was conducted at a tertiary neuroscience centre in North West England. All eligible neurology trainees within the regional training programme were invited to participate using a purposive sampling strategy. Eight trainees participated across two focus groups. Discussions were audio-recorded, transcribed verbatim, and analysed using an inductive conventional content analysis approach. Two reviewers independently coded the transcripts before reaching consensus on higher-order categories and subcategories, which are presented as themes and subthemes. Results Eight neurology trainees participated across two focus groups. Five themes were identified: educational role of consultants, questioning style, learning format, learning environment and trainee anxiety, and the role of time and experience. Participants valued the case-based format of grand rounds, particularly its ability to contextualise theoretical knowledge and provide insight into consultant-level clinical reasoning and management decisions. Consultant involvement was perceived as an important educational aspect of the grand round. However, participants also identified barriers to learning, including anxiety associated with the learning environment, broad open-ended questioning, and repeated targeting of individual trainees during public questioning. Perceptions varied according to trainee seniority, with junior trainees reporting greater anxiety and reduced engagement, whereas senior trainees increasingly valued grand rounds as preparation for independent consultant practice. Conclusion Neurology trainees viewed the grand round as a valued educational activity, particularly for contextualising theoretical knowledge and observing consultant-level clinical reasoning and management decision-making. However, trainees perceived the educational value of grand rounds to be influenced by questioning style, psychological safety, and trainee seniority. Greater consideration of these factors may help optimise the perceived educational value of grand rounds. Further evaluation in other neuroscience centres would help determine the transferability of these findings.

In this article, the authors explore the topics of grief and loss through individual vignettes, sharing stories of grief ranging from the loss of identity, the loss of a parent or loved one, and the cultural divides that make nuanced care decisions more challenging, to working in systems that may fail us and our patients. They explore the idea of nested spheres of grief that span from the individual to societal and cultural realms. Each vignette reflects the depth and complexity of their personal experiences and emotions. These moments of grief may result in moral distress, but also present opportunities to rethink and reinvent flawed systems. The authors' individual experiences of grief have brought them together to form a community of like-minded practitioners across multiple disciplines. They seek to honor their losses and harness the power of grief to improve the care they provide patients and each other. The nested model of interconnecting spheres of grief they propose may prove useful as a framing device to help all of us name our often nuanced, challenging, and complex experiences with grief. The paper concludes with a call to action, which is voiced as a priority moving forward.

Prior work demonstrates that earlier trauma exposure increases the risk of posttraumatic stress disorder (PTSD) after a subsequent trauma, and cross-sectional work has also identified sexual violence (SV) as the form of traumatic stressor with the greatest conditional risk for PTSD. However, little work explores these findings longitudinally with a comparison group with no history of SV. To examine the differences in PTSD symptoms after a new incident of trauma exposure in survivors with and without an earlier history of SV. In this case-control study, data from a longitudinal cohort sample of patients enrolled in the Advancing Understanding of Recovery After Trauma (AURORA) study were examined. Participants were admitted to emergency departments due to a traumatic injury (primarily motor vehicle crash), and they were followed up for 1 year after emergency department (ED) admission. They were recruited within 72 hours of ED admission and then assessed at 5 time points (2 weeks, 8 weeks, 3 months, 6 months, 12 months) after their injury. Participants were a diverse and heterogeneous sample of individuals admitted to EDs across the US. Study data were evaluated from January 2025 to March 2026. Earlier history of SV as assessed at ED admission using the Childhood Trauma Questionnaire and the Life Events Checklist. Symptoms of PTSD as assessed by the PTSD Checklist for DSM-5. The study sample included 2423 individuals (mean [SD] age, 36 [13] years; 1566 female [64.6%]), 1270 whom (52%) reported an earlier history of SV. At every time point, participants with a history of SV demonstrated significantly elevated symptoms of PTSD (&#x3b2;&#x2009;=&#x2009;4.62; 95% CI,&#x2009;3.09-6.21; P&#x2009;<&#x2009;.001) compared with those without a history of SV, even after controlling for earlier nonsexual trauma exposure. Within the group with prior SV, the PTSD symptoms that remained the highest across time points were hypervigilance symptoms (criterion E), although negative alterations in cognition and mood (criterion D) were the symptom cluster that recovered most slowly. Results of this case-control study indicate that having a history of SV was associated with elevated symptoms of PTSD and slower symptom recovery after a subsequent nonsexual trauma. These results raise important considerations for clinicians, regardless of whether or not they self-identify as working specifically with survivors of SV.

Rodent health-monitoring programmes are essential for maintaining colony health, supporting health-related aspects of animal welfare and personnel biosafety, and providing relevant contextual information for the interpretation of experimental data. Subclinical infections may remain unnoticed while influencing animal physiology, experimental variability, and colony-management decisions. However, long-term retrospective descriptions of pathogen trends and programme-level changes in conventional animal facilities remain limited. This retrospective study aimed to describe long-term trends in microbiological findings in a conventional rodent facility, identify recurrent or emerging pathogens, and explore how observed changes over time coincided with programmatic modifications in housing, husbandry, hygiene, personnel training, and diagnostic procedures. We performed a retrospective analysis of 20 years of health monitoring (March 2006-December 2025) in a conventional neuroscience facility housing mice and rats. The dataset comprised 135, 558 diagnostic assays (pathogen-specific test records). Positivity to pathogens was defined as positives/(positives+negatives), with 95% Wilson confidence intervals. Temporal trends were tested using binomial logistic regression on yearly aggregated counts (odds ratio per year), with pathogen-level p-values controlled by Benjamini-Hochberg FDR. Genotype comparisons were restricted to binary batches (Genetically Modified vs Non-Genetically Modified), and seasonality to predefined surveillance months. Overall positivity for the presence of pathogens showed a significant decrease over years in both species (p<0.001). Genotype effects were significant in mice (p<0.001) but not in rats (p=0.144). Seasonality was significant in mice (p<0.001) but not in rats (p=0.24). Continuous health monitoring highlighted species and subgroup-specific patterns relevant to risk assessment and colony management. Over two decades, progressive and structured improvements in health-surveillance practices, together with adaptive management procedures and qualified staff training, coincided with a sustained decrease in pathogen positivity. These improvements support a welfare-oriented and progressive refinement- informed approach embedded in an institutional commitment to animal health, personnel well-being, biosafety, transparent communication, and responsible colony management.

Reactive gliosis serves as a characteristic feature of the pathophysiology of Alzheimer's disease (AD). Nevertheless, the influence of anesthetics on the morphological dynamics of astrocytes remains ambiguous. Employing ex vivo hippocampal slices, in this study, we explored the impacts of sevoflurane and Amyloid-&#x3b2; peptide 1-42 (A&#x3b2;1-42) oligomers on astrocytic morphology. The primary outcomes encompassed the fluorescence intensity of glial fibrillary acidic protein (GFAP), the levels of a 38-kDa GFAP breakdown product (a marker of astroglial injury), and quantitative morphometric analyses (cell volume, surface area, branch complexity, and Sholl intersections). Co-exposure to sevoflurane and A&#x3b2;1-42 led to an elevation of the 38-kDa GFAP breakdown product and a significant reduction in the mean fluorescence intensity of GFAP. Moreover, it resulted in a decrease in astrocytic volume, surface area, branch complexity, and Sholl intersections. These synergistic alterations were not observed when either treatment was administered alone. These findings imply that sevoflurane aggravates A&#x3b2;1-42-induced astrocytic dysfunction, which has implications for perioperative management in patients with AD or those at risk of developing AD.

This study qualitatively explored psychological change processes as described by participants and therapists within a phase 2a clinical trial evaluating the safety, tolerability, and preliminary efficacy of a single dose of intranasal 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; BPL-003) administered alongside psychological support and manualised cognitive behavioural therapy (CBT) for relapse prevention in alcohol use disorder (AUD). Embedded qualitative sub-study within an open-label, phase 2a, single-dose (Day 0) clinical trial with 12-week follow-up (Day 84 endpoint). Semi-structured interviews were conducted remotely with participants at Day 1 post-dose and end-of-study (Day 84). Therapists were interviewed once to triangulate participant accounts and explore perceived change processes in the context of psychological support and CBT. One drug and alcohol service and one research facility in London, UK (29 March 2023-2 July 2024). Ten participants (8 men, 2 women) with moderate to severe AUD and six therapists who worked on the study. Interviews with participants followed a topic guide covering alcohol use history and motivations; expectations, intentions and preparation; acute dosing-day experiences; perceived psychological and behavioural changes; and the perceived role of support and relapse-prevention CBT. Therapists were interviewed to provide a complementary professional viewpoint on the changes and role of support. All interviews were audio-recorded, transcribed verbatim, and analysed using an interpretative phenomenological perspective supported by iterative categorisation. Immediately after dosing, participants commonly described the experience using metaphors of a "reset", "cleansing", or "rebirth", often accompanied by emotional catharsis and rapid shifts in self-perception. They reported increased clarity regarding their relationship with alcohol, enhanced emotional openness, and improved self-compassion and interpersonal connectedness. At the 12-week follow-up, participants who maintained abstinence (n&#x2009;=&#x2009;5) described the psychedelic experience as a pivotal turning point, facilitating sustained reappraisals of identity, values, and patterns of alcohol use. They also reported greater mindfulness, cognitive flexibility, and emotional acceptance, coupled with enhanced relationship quality, better sleep, increased energy, and overall well-being. Participants who resumed moderated drinking (n&#x2009;=&#x2009;2) reported similarly increased self-awareness, reduced compulsivity, and greater emotional regulation. Therapist accounts closely corroborated these participant narratives, highlighting observed shifts in psychological flexibility, emotional openness, and adaptive behavioural responses. Therapists also noted that the psychedelic experience enabled rapid relaxation and revision of maladaptive core beliefs and promoted resilience and acceptance, even in participants with initially challenging experiences. Participant and therapist accounts indicate that a single dose of 5-methoxy-N,N-dimethyltryptamine, when embedded in a relapse-prevention cognitive behavioural therapy programme, can support meaningful shifts in self-appraisal, emotional regulation, and behavioural patterns associated with alcohol consumption.

Normal explicit/declarative memory requires a system of anatomically related structures in the medial temporal lobe that includes the hippocampus and the entorhinal, perirhinal, and parahippocampal cortex. Although extensive medial temporal lobe damage in primates causes robust anterograde amnesia, defining the contribution of the hippocampus proper has proved challenging. We revisited that enduring puzzle here, directly addressing a number of factors suspected to contribute to conflicting results across earlier studies. Among them, we explored the effects of selective hippocampus lesions produced by two common excitotoxin methods, ibotenic acid and N-methyl-D-aspartic acid. Sample sizes were substantial, and all behavioral testing was conducted postoperatively. Performance was assessed on several standard procedures designed for monkeys, including multiple variants of the delayed nonmatching-to-sample test of visual object recognition, a series of rapidly acquired two-choice object discriminations, and a delayed response test of spatiotemporal memory. We used task-specific parametric manipulations (e.g., increasing retention intervals and reduced stimulus set size) to systematically vary demands on memory and test/retest analyses to enhance sensitivity for detecting impairment. Although both lesion groups sustained substantial hippocampal damage, their performance failed to differ from that of intact controls on any task, under any key test condition, regardless of data analytic strategy. The findings constrain plausible accounts of extant discrepancies in the literature and, moreover, highlight the need for fresh perspectives on the core operating characteristics of memory mediated by the primate hippocampus. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Oxidative phosphorylation (OXPHOS) is a central function and a key indicator of mitochondrial fitness, yet studies in human tissue remain limited. Inclusion body myositis (IBM) is a progressive myopathy that lies at the intersection of aging, inflammation and mitochondrial dysfunction. We aimed to perform a comprehensive profiling of mitochondrial respiration in muscle tissue from patients with IBM. A wide battery of complementary approaches from RNA level to high-resolution respirometry on permeabilized muscle fibers was employed. The relationship between mitochondrial respiration, mitochondrial content, mitochondrial DNA (mtDNA) abnormalities and mitophagy was examined, along with the correlation with various clinical parameters to determine their clinical relevance. The study included a total of 67 patients with IBM and 45 controls. On high resolution respirometry of permeabilized muscle fibers, IBM samples exhibited reduced maximal mitochondrial respiration per tissue weight in State 3 (high substrates, high ADP) and uncoupled state with decreased coupling efficiency and higher leak control ratios. When adjusting for citrate synthase reflecting mitochondrial content, male patients had decreased State 3 intrinsic respiration, whereas female patients had greater intrinsic respiration under leak states. Complex I activity was decreased mainly in female patients, in whom complex II control ratio positively correlated with disease duration and severity. IBM was further associated with decreased RNA levels of all complexes, and lower protein expression of complex I, III, IV and V, likely related to the lower mtDNA content seen in IBM samples. Regarding the production of reactive oxygen species, IBM samples exhibited lower maximal H2O2 emission, accompanied by a higher total antioxidant capacity that positively correlated with disease duration in female patients. Lastly, correlation analyses suggested that impaired mitochondrial respiration, altered mitophagy, and reduced mtDNA content are interconnected in IBM and maybe of clinical significance. IBM is characterized by multifaceted, clinically relevant impairments in mitochondrial respiration. Future studies should further explore underlying pathomechanisms and the variation of mitochondrial respiration by disease stage.

The aim of this study was to evaluate the budget impact of introducing the subcutaneous (SC) form of ocrelizumab for patients with relapsing forms of multiple sclerosis (RMS) with high disease activity (HA) despite previous treatment or with rapidly evolving severe (RES) disease in Italy from the hospital perspective. A 3-year dynamic budget impact model with a Markov structure was developed de novo to simulate patient transitions across Expanded Disability Status Scale-defined health states. The current scenario (without ocrelizumab SC) was compared with an alternative scenario reflecting expected ocrelizumab SC uptake. Number of eligible patients reflected Italian population and projected market shares. Efficacy inputs were obtained from published literature, with adherence and persistence sourced from Italian real-world data. Unit costs-including drug administration, monitoring, adverse events, disease management, and relapse-were collected from Italian sources. Drug acquisition costs were considered in a scenario analysis. Parameter uncertainty was explored through deterministic sensitivity and scenario analyses. Over 3&#xa0;years, 22,128 patients were eligible, of whom 5389 were assumed to receive ocrelizumab SC. Ocrelizumab SC introduction would generate cumulative savings of about &#x20ac;2.0 million, mainly from reduced administration and monitoring costs, with additional savings from relapse and disease management expenditures. When drug acquisition costs were included, total savings rose to roughly &#x20ac;7.1 million. Sensitivity analyses confirmed the robustness of these findings. Ocrelizumab SC may be a cost-saving and resource-efficient option for HA/RES RMS management in Italy. By reducing administration time while maintaining the established clinical profile of the intravenous (IV) formulation of ocrelizumab, its adoption can enhance hospital efficiency and deliver meaningful budgetary savings.

Cancer neuroscience has emerged as a field that explores the bidirectional interactions between tumors and the nervous system. From this perspective, we review the pharmacological and neurobiological effects of kinase inhibitors, which are widely used as anticancer therapeutics. Certain kinase inhibitors not only exert potent antitumor activity but also modulate neural function as a consequence of kinase inhibition. Representative examples include small molecules and therapeutic antibodies targeting the tropomyosin receptor kinase (Trk), rearranged during transfection (RET), vascular endothelial growth factor/ vascular endothelial growth factor receptor (VEGF/VEGFR), epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) signaling pathways. These agents influence the nervous system through molecular mechanisms, examples of which include TrkA-mediated pain perception and growth differentiation factor 15/RET signaling-dependent appetite regulation. Elucidating these mechanistic intersections between oncogenic and neural signaling can broaden our understanding of tumor-nerve crosstalk.

The pathophysiology of epilepsy remains poorly understood. One of the less explored areas is the role of the lung-brain axis, a sophisticated and intricate bidirectional connection between these two vital organs. Inhaled air pollutants can disrupt lung microbiome homeostasis. This disruption, analogous to gut dysbiosis implicated in neurological conditions, may contribute to epilepsy pathogenesis. Here, we review the existing evidence and theoretical foundations supporting the hypothesis that dysbiosis within the lung microbiota may play a role in the pathophysiology of epilepsy. This includes the links between environmental factors (particularly air pollution) and epilepsy susceptibility; the associations between lung-intrinsic microbiota dysregulation and neurological dysfunction; and the underlying molecular, immunological, and neural mechanisms that enable the lung-brain axis to modulate epileptogenesis. Furthermore, we outline the possible potential pathogenic mechanisms of epilepsy from the perspective of the microbiota-lung-brain axis, offer fresh perspectives on the pathophysiology of epilepsy, and explore potential new research directions related to the lung-brain axis and epilepsy. We propose that a deeper understanding of the function of the lung-brain axis will provide new insights into the etiology, diagnosis, prognosis, and treatment of epilepsy.

Phantom Limb Pain (PLP) frequently occurs after limb amputation and often negatively influences daily functioning. Phantom Motor Imagery (PMI) treatment intends to decrease PLP by imagining phantom movements guided by extended reality techniques. The aim of this study was to investigate the experiences of individuals with PLP after limb amputation who underwent PMI treatment, and to explore the consequences of PMI treatment on daily functioning. A qualitative study was performed, consisting of semi-structured interviews one month after PMI treatment among eight Dutch participants with chronic PLP after a lower-limb amputation (mean age 63&#x2009;years, 50% female). Data analysis followed the Framework Method. Most participants experienced better control of the phantom limb after PMI treatment. The treatment was considered mentally demanding. PLP decreased in most participants, enhancing mood, sleep and daily participation. Some experienced recurrence of PLP post-treatment and reported limited knowledge about PLP. PMI treatment has the potential to reduce PLP, and consequently improve quality of life. Intermittent PMI sessions after completing the initial treatment would be advised for lasting effect. Regularly imagining moving their phantom limb could be beneficial for patients. Clinicians should educate patients about PLP. Participants described phantom motor imagery treatment as mentally demanding but still viewed it as a worthwhile option when they experienced noticeable improvements.In a research setting, individuals receiving phantom motor imagery treatment have described experiencing less phantom limb pain, resulting in better mood, sleep, and quality of life.Visual feedback in an augmented reality and virtual reality environment appears to be helpful for imagining movements of the phantom limb.Long-term, albeit intermittent, treatment aimed at controlling movements of the phantom limb should be considered for lasting effect.Understanding about phantom limb pain is limited among individuals with an amputation and clinicians should educate patients.

The main goal of any arteriovenous malformation (AVM) intervention is to eliminate the risk of haemorrhage, which can be achieved by complete extirpation, endoluminal occlusion, or obliteration of the AVM. Radiosurgery is a minimally invasive intervention that can be performed alone or in combination with other treatments. This study aimed to determine the rate of AVM obliteration in our study population and to explore the effect of AVM characteristics, treatment mode, and treatment parameters on the obliteration rate. Three centres participating in this study obtained approval from the institutional review board and ethics committee. A total of 104 patients from among 146 were identified according to the inclusion and exclusion criteria. Data retrieved from each centre includes demographic review, AVM characteristics such as size, volume, location, eloquence, venous drainage, aneurysm association, treatment mode, and parameters. Univariate and multivariate logistic regression analyses were performed to determine the potential predictors of clinical outcome, AVM obliteration, and early obliteration. Of the 104 patients who underwent radiosurgery, 45 (43.3%) were obliterated, and 88.9% were obliterated within three years. The independent predictors of AVM obliteration were low Spetzler-Martin grading (P = 0.005), dose > 22 Gy (P = 0.001), low radiosurgery-based AVM grading scale score (P = 0.037), low Virginia radiosurgery AVM scale score (P = 0.045), fraction (P = 0.002), and treatment mode (P = 0.025). Volume was the independent predictor of early obliteration (P = 0.013). The presence of a neurological deficit was the independent predictor of the clinical outcome (P = 0.018). Identifying predictors of good outcomes for patients who are suitable for radiosurgery is important to ensure optimal AVM treatment.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with an active trial landscape that relies on the sensitivity of selected clinical trial endpoints. Traditional clinical outcome assessments perform well in trials but lack strong psychometric properties and may not detect small but clinically meaningful disease progression. Digital health technologies offer a promising alternative for tracking ALS disease progression. This study assessed the feasibility of remote digital monitoring in ALS using a comprehensive battery of prescribed home-based assessments via a smartphone, a wearable device, and a computer-based mouse-clicking task. Participants completed weekly remote assessments, including motor and speech tasks via a smartphone app and a computer mouse-clicking task for 24 weeks. They also participated in 3 remote telephone visits in weeks 1, 13, and 25. Reliability, minimal detectable change, and correlations with self-reported ALS Functional Rating Scale-Revised subdomain scores were calculated for 8 features across the speech, fine motor, and gross motor smartphone app tasks and for all 32 features from the computer mouse-clicking task. Sensitivity to longitudinal change was assessed for the 8 smartphone-derived features and for a representative subset of 8 computer mouse-clicking features. Forty-two participants (19 with ALS and 23 controls) completed 10,237 smartphone assessments and 459 computer mouse-clicking sessions. Baseline discriminative models differentiated ALS from controls with AUC values of 0.75-0.92. Digital measures correlated strongly with self-reported ALS Functional Rating Scale-Revised subdomain scores. Both participants with ALS and controls demonstrated improvement in fine motor and speech measures, with the exception of nondominant-hand pegboard performance, which declined in the ALS group. Improvements were smaller in participants with ALS, leading to increasing group differences over time, although only one feature showed a statistically significant separation over the 24 weeks. Gait and balance performance declined in both groups, with greater but nonsignificant separation observed for balance measures. These findings support the feasibility of digital remote assessments in ALS, demonstrate the ability to discriminate between ALS and controls based on certain features collected from speech, fine, and gross motor tasks, and in some cases, quantify functional decline over time. Further research is necessary to explore the natural history of these features longitudinally in larger cohorts of participants with ALS over extended periods to enable their potential integration into clinical trials.