Search Results (1,555)

Digital Twins (DTs) are virtual, patient-specific representations that integrate real-time data to model, predict, and optimize biological and clinical processes. In neonatology, DTs are gaining attention as powerful tools for managing the profound physiological complexity and variability of newborns, particularly preterm infants requiring intensive care. Emerging applications include cardiopulmonary modeling, prediction of sepsis and necrotizing enterocolitis (NEC), optimization of mechanical ventilation, individualized nutrition, and longitudinal monitoring of neuromotor development. This review synthesizes current research on neonatal digital twins, highlighting clinical use cases and ethical considerations. We discuss persistent challenges, including limited data availability, rapid developmental change, model validation, and regulatory oversight. Finally, we outline a roadmap for integrating DTs into neonatal intensive care units (NICUs) and identify future research priorities, including multi-organ integration, predictive closed-loop systems, and personalized life-course care trajectories. Full article

Background/Objectives: Neurological complications remain a critical source of morbidity and mortality following pediatric cardiac surgery for congenital heart disease (CHD). While advances in surgical and perioperative care have improved survival, the incidence of postoperative neurological events and their associations with perioperative characteristics remain incompletely characterized in heterogeneous pediatric populations. This study aimed to assess the incidence of postoperative neurological complications and to examine factors associated with adverse clinical outcomes in pediatric patients undergoing cardiovascular surgery. Methods: This retrospective, single-center study included 210 pediatric patients (<18 years) who underwent open-heart or major cardiovascular surgery with cardiopulmonary bypass at Medipol University Hospital between January 2021 and January 2022. Univariable logistic regression analyses were performed to explore associations between perioperative variables, postoperative neurological complications, and in-hospital mortality. Results: Of the study population, 119 patients (56.7%) were male and 91 (43.3%) were female; 117 patients (55.7%) were younger than 2 years of age. The most common procedures included ventricular septal defect repair (18.6%) and tetralogy of Fallot repair (13.3%). Postoperative neurological complications occurred in 20 patients (9.5%). Median postoperative intubation duration and intensive care unit (ICU) stay were significantly longer among patients with neurological complications (p < 0.001). In-hospital mortality occurred in 18 patients (8.6%). Postoperative neurological complications, reoperation, prolonged intubation, extended ICU stay, and longer cardiopulmonary bypass duration were significantly associated with in-hospital mortality. Conclusions: Postoperative neurological complications were associated with prolonged ICU stay and increased in-hospital mortality. These findings emphasize the clinical importance of close neurological monitoring and perioperative strategies aimed at preserving cerebral perfusion and minimizing cardiopulmonary bypass duration in pediatric cardiac surgery. Full article

Research on unaccompanied foreign minors remains limited due to the low scientific visibility of this population and the complexity of trauma-related neurodevelopment. This study presents a scientometric analysis of international literature (2007–2025) to identify trends, collaboration networks, thematic clusters, and research gaps on trauma and neuroeducation in this field. Using data from Scopus and Web of Science, methodological, contextual, and thematic variables were coded and analysed through bibliometric and network techniques. Results show a 91% growth in publications since 2008, following an exponential pattern (r² = 0.91), with 90 authors organised into 23 collaboration clusters and an average collaboration index of 0.80. Despite growing inter-institutional networks, research remains concentrated in France, the United States, and the United Kingdom–Africa axis. The study concludes that the field is entering a phase of consolidation, shifting from predominantly clinical perspectives toward preventive and integrative neuroeducational approaches that combine relational, cultural, and educational dimensions to mitigate the effects of migratory trauma. Full article

Chromatin organization during postnatal development is very important for establishing neuronal function and may be disrupted in neurodevelopmental disorders that are associated with impaired brain function. Both the Methyl CpG-binding protein 2 (MeCP2) and the linker histone H1 are important chromatin regulators. Still, their developmental expression patterns and functional interactions across diverse genetic backgrounds are not well understood. This study examined changes in histone H1, histone H3, and MeCP2 levels in CD1 and C57BL/6 mice in two different strains, in the liver, cerebellum, and cerebral hemispheres obtained at two adolescent developmental stages [P21 (postnatal day 21) and P56]. We show that both strains have significant cerebral-specific increases in MeCP2 and H1, while H3 levels remain consistent. The CD1 strain exhibited hepatic H1 elevation between early (P21) and late (P56) adolescence, which was absent in the C57BL/6 strain. This highlights possible strain-dependent postnatal dynamic chromatin organization. Analysis of Mecp2^T158M (Mecp2^tm4.1Bird) mutant mice showed compensatory H1 elevation in the Purkinje layer of the cerebellum, indicating possible functional relation between these two chromatin-bound proteins. Despite having minimal MeCP2 protein levels, mutant mice had higher amounts of Mecp2 transcripts, suggesting post-transcriptional/post-translational regulations. Our results demonstrate that H1 and MeCP2 are subject to coordinated developmental control with possible interplay with the chromatin structure. Full article

Background: Neurodevelopmental disorders (NDDs) are a heterogeneous group of conditions characterized by cognitive, behavioral, and developmental impairments, frequently linked to structural genomic alterations. Copy number variants (CNVs) involving chromosome 16, particularly the short arm 16p, are recognized contributors to neurodevelopmental variability. Despite increasing international evidence, data from Italian clinical cohorts are still limited. Methods: We investigated 1200 patients referred for genetic evaluation due to suspected NDDs, including autism spectrum disorder (ASD), intellectual disability (ID), global developmental delay, and language impairment. All individuals underwent array comparative genomic hybridization (a-CGH) analysis, and identified variants were correlated with detailed clinical, cognitive, and behavioral assessments. The analysis focused on recurrent CNVs at 16p11.2, 16p13.3, and 16p13.11, regions containing dosage-sensitive genes relevant to neurodevelopment. Results: CNVs involving the 16p region were identified in 96 patients (8% of the cohort), encompassing both deletions and duplications. Deletions were mainly associated with developmental delay, language deficits, and ASD-related features, whereas duplications were more frequently linked to behavioral dysregulation, attentional deficits, and variable cognitive impairment. Marked phenotypic variability was observed among individuals carrying similar CNVs, suggesting the contribution of modifying genetic or environmental factors. In a subset of patients, additional CNVs were identified, potentially exacerbating clinical severity, consistent with the two-hit model. Conclusions: This study confirms a strong association between recurrent 16p CNVs and a wide spectrum of neurodevelopmental phenotypes in an Italian clinical cohort. The findings emphasize the diagnostic utility of systematic genomic screening and the importance of an integrated genotype–phenotype approach to improve clinical interpretation, management, and genetic counseling in NDDs. Full article

ALS is a multistep disease, in which (epi)genetic, environmental, and age-related processes, including senescence, converge over decades to reduce resilience resulting in self-sustaining symptomatic disease. The multistep model visualizes five to six impactful events in sporadic ALS, but fewer in those carrying high-penetrance mutations, such as SOD1, FUS, or C9orf72 expansions. The timing, duration, and cumulative effects of specific steps are presumed to have individual variability but, the steps themselves are inferred since they have not been observed and remain agnostic as to biological identity. Nevertheless, the model gives an opportunity to integrate genetics, aging, environmental exposures, and systems-level vulnerability into a single framework. Acting as step modifiers, environmental exposures including trauma lower the threshold for step acquisition, accelerate the accumulation of steps, influence the anatomical site of disease onset, and unmask preclinical disease. Because ALS emerges from the gradual collapse of multiple layers of biological robustness, tackling a single pathway will be insufficient and the multistep model forces a reconsideration of therapeutic timing and strategies. Protection against early-life insults, anti-aging, and anti-senescent therapies may curtail step accumulation preventing ALS from exceeding threshold and disease manifestation. Full article

Introduction: Exercise has proven to be an excellent tool for improving health in individuals with hypertension. A particularly interesting environment for performing exercise is the aquatic medium, whose unique properties have shown effectiveness in reducing blood pressure values. Objective: Our objective was to provide an update on the available scientific evidence regarding the effects of aquatic exercise on individuals with hypertension. Methods: A systematic search was conducted in the databases PubMed, Web of Science, CINAHL, Sport Discus, Medline, Scopus, and PEDro. Methodological quality was assessed using the PEDro scale, and the risk of bias was evaluated using the RoB 2 tool. Results: Eleven studies were included, with a total of 402 participants, obtaining a mean score of 5.7 on the PEDro scale. Five studies presented a high risk of bias, four showed a low risk, and in two, the risk was unclear. The most used therapeutic exercises in the analyzed interventions were water walking, aquatic mobility and strength exercises, aquatic high-intensity interval training, and aquatic calisthenics. Notably, none of the interventions included swimming. Conclusions: Aquatic exercise appears to be associated with reductions in blood pressure in individuals with hypertension; however, these findings should be interpreted cautiously due to the methodological limitations and heterogeneity of the included studies. Full article

Neuroplacentology is an emerging field of research supporting that the placenta actively contributes to the fetal brain development through the release of bioactive molecules. Recent angiogenesis-focused data showed that prenatal alcohol exposure (PAE) disrupts inter-organ gene expression between the placenta and fetal cortex. The present study aimed to perform the first comprehensive and untargeted analysis of a murine placenta–cortex transcriptomic database of PAE. Gene lists from a recently NCBI-deposited PAE Placenta–Cortex transcriptomic database were analyzed using g:Profiler for unbiased functional profiling querying Gene Ontology, KEGG, and Reactome databases. Genes intersecting with cell–cell communication terms were submitted to STRING and ShinyGO analyses to identify enriched protein–protein interactions and pathways. Several ligand or receptor candidates were then validated by Western blot. g:Profiler revealed 21 enriched GO functional maps, seven KEGG pathways, and six Reactome pathways, of which 11 were related to cell-to-cell communication. STRING analysis exhibited substantial protein–protein interaction enrichments supporting that proteins belonging to the functional maps and pathways are biologically connected. Notably, 38 ligands or receptors from endocrine families including angiotensinogen, leptin, somatostatin, or PACAP were identified. Western blot analysis of protein candidates showed different validation patterns. In particular, the PACAP receptor family confirmed transcriptomic findings and revealed sex-dependent PAE-impacted expression profiles. The present study indicates that PAE is associated with alterations in the transcriptomic placenta–cortex expression profile, including changes in the expression ratios of several ligands and/or receptors implicated in key physiological pathways such as energy balance, vascular development, and neurogenesis. These transcriptomic associations suggest that altered placenta–fetal brain signaling at the gene expression level may be involved in alcohol-induced neurodevelopmental disorders, highlighting the need for future functional validation studies. Full article

Background: Listeria monocytogenes infection during pregnancy remains an underrecognized cause of severe neonatal disease, frequently leading to central nervous system (CNS) involvement with high mortality and long-term neurological sequelae. Case presentation: We report a case series of four neonates with confirmed neonatal listeriosis and neurological complications, managed in a tertiary neonatal intensive care unit (NICU). Clinical features, microbiological findings, neuroimaging, treatments, and outcomes were analyzed. Our cases presented with early-onset disease and severe clinical courses, including sepsis, meningitis, ventriculitis, hydrocephalus, and seizures. Neuroimaging revealed extensive CNS injury, ranging from intraventricular hemorrhage to multiloculated hydrocephalus. Outcomes varied from near-normal neurodevelopment to profound neurological impairment, despite appropriate antimicrobial therapy. A narrative review of previous cases of neonatal listeriosis was also performed to contextualize our findings. Conclusions: Neonatal listeriosis remains associated with severe neurological morbidity. Early recognition, advanced neuroimaging, multidisciplinary management, and preventive maternal strategies are essential to improve outcomes. Full article

The complement system is a central component of innate immunity with established roles in host defense and emerging functions in neurodevelopment, synaptic remodeling, and neuroimmune communication within the central nervous system (CNS). In parallel, advances in nanotechnology have not only enabled targeted strategies for CNS drug delivery but have also revealed that many nanomaterials interact with and activate complement, influencing biodistribution, safety, and inflammatory responses. Opioid use disorder (OUD) is increasingly recognized as a condition associated with chronic neuroimmune dysregulation involving glial activation, altered cytokine signaling, and blood–brain barrier (BBB) disruption. However, direct experimental or clinical measurements of complement activation in OUD remain limited. Current evidence linking complement pathways to opioid exposure is derived largely from indirect observations, including transcriptomic alterations, glial phenotypes, and inflammatory signatures in preclinical and translational models, which collectively suggest, but do not yet definitively establish, complement involvement in opioid-induced neuroimmune signaling. This review synthesizes current knowledge at the intersection of complement biology, nanomedicine, and opioid-associated neuroimmune changes. It distinguishes well-established mechanisms of complement activation by nanomaterials from emerging and inferential evidence linking complement signaling to opioid exposure. This hypothesis-generating framework integrates complement signaling with opioid receptor and TLR4 pathways in glial and endothelial compartments, examining their potential protective and pathological CNS roles while outlining the translational promise and current evidence gaps of complement-aware nanotechnologies for addiction neuroscience. Full article

Excessive right heart load imposes an acute or chronic injury on the right ventricle (RV), predisposing critically ill neonates and cardiac surgical patients to RV failure, low cardiac output syndrome, and death. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that improves ventilation–perfusion matching and unloads the RV without systemic hypotension; nonetheless, its application beyond established neonatal indications remains contentious. Our review synthesizes current mechanistic, translational, and clinical evidence regarding iNO use in three major settings characterized by excessive RV load: (1) neonatal pulmonary hypertension, particularly PPHN; (2) acute and chronic RV overload in older children and adults, including secondary pulmonary hypertension, acute respiratory distress syndrome (ARDS), and acute pulmonary embolism; and (3) perioperative and post-cardiopulmonary bypass (CPB) management in congenital and adult cardiac surgery. In term and near-term infants with hypoxic respiratory failure, pivotal randomized trials show that iNO consistently improves oxygenation and reduces extracorporeal membrane oxygenation (ECMO) use, but this has little effect on survival and long-term neurodevelopment. In ARDS and other adult critical-care indications, iNO provides transient improvements in gas exchange and RV performance without reducing mortality or ventilator duration, and meta-analyses signal an increased risk of acute kidney injury, particularly with prolonged use. In contrast, perioperative studies around CPB demonstrate that prophylactic postoperative iNO and intra-CPB nitric oxide administration can attenuate pulmonary hypertensive crises, facilitate separation from CPB, shorten ventilation and intensive care stay, and, in selected high-risk cohorts, may reduce cardiac surgery-associated acute kidney injury, although survival benefits remain unproven. Across these scenarios, iNO should be used judiciously and in a pathophysiology-driven manner as a time-limited, targeted adjunct to stabilize patients with documented or anticipated RV strain rather than a disease-modifying therapy. Future work should refine patient selection, timing, dosing, and weaning strategies, and define the long-term safety and cost-effectiveness of iNO within contemporary multimodal RV support pathways. Full article

The aim of this narrative review is to critically assess the renoprotective effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in managing albuminuria among patients with type 2 diabetes mellitus within the framework of personalized medicine. By integrating current evidence from clinical trials and meta-analyses, the review highlights how GLP-1RAs not only enhance glycemic control but also reduce blood pressure, induce weight loss, and mitigate inflammatory responses. While these given factors may vary according to individual patient profiles, they also collectively contribute to slowing the progression of diabetic kidney disease (DKD). Additionally, the discussion emphasizes the dual cardiovascular and renal benefits from these agents, underscoring their role in reducing albuminuria and preserving renal function. The review also identifies gaps in knowledge, suggesting future research directions for optimizing patient selection and treatment regimens to maximize therapeutic benefits. Full article

The endocannabinoid system is a ubiquitous neuromodulatory network that links internal physiological state to neural circuit function across the brain. While its roles in memory, reward, pain, and motor control are well established, its contribution to olfactory processing has only recently gained attention. This review synthesizes the current knowledge on the anatomical, cellular, and functional interactions between the endocannabinoid system and the olfactory pathway, from the olfactory epithelium and main olfactory bulb to higher order cortical targets. We highlight how endocannabinoid signaling, primarily via cannabinoid receptor type 1 (CB1), shapes synaptic transmission within olfactory bulb microcircuits, modulates centrifugal feedback, and adjusts sensory gain in a state-dependent manner, particularly in relation to hunger, feeding behavior, stress, and reward. In addition, we review evidence that the endocannabinoid system regulates olfactory neurodevelopment and adult neurogenesis by influencing neural stem cell proliferation, migration, and integration into existing circuits. Emerging links between endocannabinoid signaling, olfactory dysfunction, neuropsychiatric disease, metabolic disorders, and neurodegeneration underscore the translational relevance of this system. We also discuss methodological challenges inherent to studying endocannabinoid signaling and outline future directions, including circuit-specific targeting and intranasal delivery strategies. Together, these findings position the olfactory system as a powerful and accessible model for understanding how endocannabinoids couple internal state to perception and behavior, with important implications for therapeutic development. Full article

Background: Preterm birth is a significant risk factor for neurodevelopmental delays, but the appropriate use and timing of age correction for developmental assessment remain debated. Objective: This study investigated psychomotor development in preterm children at two years of age, with the aim of clarifying whether age correction remains necessary at this stage, particularly across different gestational age groups. Methods: A total of 161 preterm infants were assessed at a mean chronological age of 25.4 months (mean corrected age: 23.3 months) and compared with two control groups of typically developing children matched for gender and either corrected age (Control–Corr, N = 88) or chronological age (Control–Chron, N = 87). The preterm group was further stratified by gestational age: extremely preterm (<28 weeks), very preterm (28–31 weeks), and moderate-to-late preterm (32–36 weeks). Cognitive, Language (Receptive, Expressive), and Motor (fine, gross) scales of Bayley-III were analysed using t-tests and MANOVAs. Results: Using corrected age, preterm children showed a selective profile, with deficits in Receptive Language, borderline mean score in Gross Motor, and preserved performance in Cognitive, Expressive Communication, and Fine Motor. When compared with controls of the same age, significant differences emerged in the Cognitive, Language, and Gross Motor, but not Fine Motor, domains. In contrast, scoring by chronological age produced a generalised delay, with preterm children performing significantly worse than chronological-age controls across all domains. Subgroup analyses further showed that extremely preterm children already displayed marked Language vulnerabilities at corrected age, which became more severe with chronological scoring and extended to other domains. Very preterm children also fell into the deficit range in Cognitive, Language, and Gross Motor scales/subscales when chronological age was applied, whereas moderate-to-late preterm children performed comparatively better. Conclusions: Developmental assessment using corrected age remains essential at least until 24 months, especially for extremely and very preterm children, to avoid substantial overestimation of developmental difficulties. Chronological scoring, while helpful to highlight persistent vulnerabilities, may inflate delay classification if used too early. Tailoring correction strategies by gestational age and developmental domain could provide a more accurate and clinically meaningful representation of preterm children’s developmental trajectories. Full article