BioCruces Health research Institute

Ocular syphilis in the Iberian Peninsula shows a wide clinical spectrum and frequent posterior segment involvement. Most patients achieved favourable serological and visual outcomes. These findings support the effectiveness of standard therapies and highlight the need for early diagnosis, especially in high-risk populations.

The demand for children and adolescent mental health crisis services has risen dramatically in recent years, yet evidence on real-world implementation models remains limited. Rapids is a community-based crisis intervention service developed within Lambeth Children and Adolescent Mental Health Services (CAMHS) at South London and Maudsley NHS Foundation Trust. The primary aim of this study was to examine how clinical presentations, risk profiles, and service outcomes changed over time among children and adolescents accessing Rapids over a 6-year period. We also aimed to describe the characteristics of individuals accessing Rapids. This service evaluation used routinely collected clinical data from all children and adolescents up to 18 years who accessed Rapids between January 1, 2019, and December 31, 2024. Sociodemographic, diagnostic, pharmacological, and risk-related variables were evaluated. Diagnoses were coded using International Classification of Diseases, 10th Revision (ICD-10) criteria. Descriptive and inferential analyses were conducted to assess changes in clinical presentations and service outcomes. In total, 325 children and adolescents were included (mean age = 15.5 years, 61.8% females, 64.6% non-White). Anxiety disorders (29.5%), depressive disorders (42.2%), and autism spectrum disorder (33.5%) were the most common diagnoses. Inpatient admissions increased (1.5%-5.8%, p = 0.043), and high risk to self also rose notably (19.5%-31.7%, p < 0.001). Referrals accepted to adult services decreased significantly over time (38.5%-16.8%, p < 0.001). Diagnostically, eating disorders increased (3.7%-10.0%, p = 0.032), whereas emotionally unstable personality disorder traits decreased (14.1%-7.4%, p = 0.049). Rapids has evolved into an established model of crisis care within CAMHS, addressing acute needs through timely community-based interventions. We observed meaningful temporal changes in the clinical acuity, diagnostic profile, and service use outcomes of young people presenting to our community-based CAMHS crisis service. Our findings support the feasibility and scalability of intensive community-based crisis care and highlight the need for sustained investment in culturally responsive, multidisciplinary service models.

Parkinson’s disease (PD) is characterised by progressive dopaminergic neurodegeneration, alpha-synuclein (α-syn) aggregation, and neuroinflammation. Clinical and experimental studies suggest that sex influences disease onset, progression, and treatment response, yet its impact on α-syn-mediated pathology remains incompletely understood. In this study, we investigated sex-dependent progression of behavioural and neuropathological alterations in a mouse model overexpressing A53T α-syn. Male and female C57BL/6J mice received bilateral intranigral injections of adeno-associated viral vectors encoding mutant A53T α-syn or empty vectors. Motor performance was assessed at 60 and 120 days post-surgery using open field, wire hang, pole, and balance beam tasks complemented by automated behavioural analysis (DeepLabCut, SimBA). Brains were processed for immunohistochemical evaluation of α-syn accumulation, tyrosine hydroxylase (TH) expression, axonal integrity, and glial activation. A53T α-syn overexpression induced early subtle motor deficits primarily in males, accompanied by increased immobility on the balance beam despite preserved substantia nigra compacta neuron counts. By 120 days, striatal TH immunoreactivity was markedly reduced in α-syn mice. An integrated axonal degeneration index, combining TH optical density and swelling counts, revealed a faster progression of striatal axonopathy in males. Both sexes showed enhanced striatal astrogliosis, indicating α-syn-driven neuroinflammation independent of sex. These findings identify early axonal degeneration and reactive astrogliosis as key pathological events preceding neuronal loss in A53T α-syn mice. Importantly, the pronounced male vulnerability highlights sex as a critical biological variable in modelling PD progression and in developing precision-based neuroprotective strategies.

There is a lack of high-quality data to inform risk-stratified long-term thrombosis prevention strategies in patients with persistently positive antiphospholipid antibodies (aPL). We aimed to determine independent clinical and biologic predictors of thrombosis among persistently aPL-positive patients. Patients positive for aPL according to the Revised Sapporo Classification Criteria are eligible for inclusion in the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Registry. Registrants with at least 1 year of follow-up were included in this study. We fit Cox proportional hazards models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for independent predictors of thrombosis. In unadjusted analyses, based on 1067 patients with a mean follow-up of 4.43 years (4,727 person-years), history of thrombosis, hematologic disease (autoimmune haemolytic anaemia and/or thrombocytopenia), microvascular disease, obesity, renal disease, sedentary lifestyle, baseline anticoagulant use, and family history of early cardiovascular disease occurred more frequently (P < .05) among patients with new thrombosis (n = 93) than among those without new thrombosis (n = 974). After adjustment, independent predictors of new thrombosis were history of thrombosis (HR 2.34, 95% CI 1.14 to 4.81, P = .02) and hematologic disease (HR 1.95, 95% CI 1.19 to 3.18, P = .01); there was a trend for history of microvascular disease (P = .06) and obesity (P = .08). In this prospective analysis, history of thrombosis and hematologic disease each conferred an approximately twofold increased risk of new thrombosis in persistently aPL-positive patients. These findings can guide future clinical trial designs and inform patient management decisions.

Hybrid Microdiscs In their Research Article (10.1002/adfm.202525146), Maite Insausti, Idoia Castellanos-Rubio, and co-workers present a modular microfabrication strategy for developing multifunctional magnetic microdiscs. The tunable size and composition of these inorganic–polymer microdiscs govern their biological fate: larger discs remain at the cell surface as micro-implants, whereas smaller ones are internalized to deliver cargo intracellularly, all while enabling magnetic guidance and controllable magnetothermal activation. Artwork created in collaboration with Norarte Visual Science S.L.

Abstract Brain tumours invade neural tissue, disrupting the functional organisation of neural networks. This disruption can trigger compensatory neuroplastic mechanisms that help preserve cognitive function despite pathological burden. Resting-state functional connectivity (rs-FC) provides a valuable approach for examining these alterations, yet the scope and trajectory of network-level changes remain unclear. In this study, we used rs-FC to characterise compensatory responses induced by left-hemisphere brain tumours affecting the integrity of the language network. The comparison of connectivity patterns at diagnosis and after surgery allowed us to track the temporal progression of these patterns. Relative to healthy participants, patients showed significant deviations in pre-surgical rs-FC, with widespread changes involving the dorsal attention, sensorimotor, frontoparietal, default mode, and cerebellar networks. These differences persisted post-surgically, with no significant longitudinal modifications. Network-level alterations also influenced topological properties: patients showed increased segregation while preserving global integration relative to controls. These properties changed significantly from pre- to postoperative period, with a postoperative increase in segregation and integration towards a pattern more closely resembling that of healthy controls. Furthermore, preoperative network segregation was identified as a predictor of postoperative cognitive recovery. These findings suggest that brain tumours induce network remapping, affecting functional connectivity far beyond the regions strictly related to the affected region. The observed changes in network topological organisation likely reflect the adaptive role of domain-general networks in facilitating homeostatic processes. Surgical strategies aimed at preserving these changes seem to promote sustained cognitive function, regardless of malignancy grade or lesion extent. Key points Presurgical patients show widespread inter- and intrahemispheric rs-FC alterations, reflecting tumour-driven network remapping. Network integration and segregation show longitudinal recovery, approaching neurotypical topology four months post-surgery. Preoperative network segregation predicts postoperative cognitive recovery. Importance of the Study Brain tumours disrupt large-scale brain networks, yet the extent, temporal dynamics, and cognitive relevance of these alterations remain poorly understood. Using resting-state functional connectivity, this study provides a longitudinal, network-level characterisation of tumour-induced neuroplasticity in patients with left-hemisphere lesions affecting language-related regions. Compared with prior work focused on local effects or single networks, our results demonstrate widespread inter- and intrahemispheric connectivity changes involving multiple domain-general resting-state networks, highlighting extensive network remapping beyond lesion boundaries. Importantly, we show that postoperative recovery is accompanied by a rebalancing of network integration and segregation toward a neurotypical configuration. Critically, preoperative network segregation emerges as a predictor of postoperative cognitive recovery, identifying a potential biomarker of resilience. These findings have direct translational relevance, suggesting that preserving and supporting large-scale network organisation during surgical planning may promote cognitive outcomes independently of tumour grade or lesion extent.

N6-methyladenosine (m6A) RNA modifications and reovirus infections have recently been implicated in the development of celiac disease. While viral infections are known to alter the RNA modification machinery of the host, their interplay in autoimmune tissue damage remains unexplored. In this study we employed an in vitro model combining a viral mimic with gliadin peptides to simulate celiac disease conditions, alongside the analysis of serum and intestinal biopsies from controls and patients to investigate the link between m6A methylation and viral infections in inducing autoimmune inflammation. We found elevated anti-reovirus reactivity in patients, increased antiviral gene expression and enhanced m6A levels. Notably, the expression of IRF7 was synergistically induced by the combined exposure to the viral mimic and gliadin peptides, and this is mediated through m6A methylation in its coding region and interaction with the reader protein YTHDC2. Furthermore, the reduction of m6A through METTL3 silencing or simvastatin treatment reduced IRF7 mRNA methylation and downstream proinflammatory gene expression both in vitro and ex vivo. These findings highlight m6A methylation as a modulator of antiviral responses and a potential therapeutic target in autoimmune disorders.

Bioresorbable nanopatterned scaffolds functionalized with polydopamine (PDA) and graphene oxide (GO) have been shown to promote the differentiation of murine neural stem cells (mNSCs) toward neural and glial lineages. Herein, we aim to evaluate the compatibility of these scaffolds for the culture and differentiation of both human embryonic (hESCs) and induced pluripotent (hiPSCs) stem cells. Our results indicate that PDA and GO scaffolds support the topographic alignment of hESCs and hiPSCs cultures, while preserving their pluripotency characteristics. Upon differentiation, PDA and GO scaffolds guide cell specification toward the neuroectoderm germ layer and the neural crest. This promotes enhanced differentiation into both neural and supportive glial cells of the central nervous system (CNS), as well as Schwann cells of the peripheral nervous system (PNS). Moreover, nanopatterned scaffolds also support the differentiation of hESCs and hiPSCs toward endothelial precursors. These findings establish a novel culture platform that enables combined differentiation pathways, potentially relevant for applications in personalized medicine and regenerative cell therapy.