Search Results (87)

Periventricular nodular heterotopia (PVNH) is a genetically heterogeneous malformation of cortical development with variable neurological outcomes. Among recessive forms, ARFGEF2-related disorder is uniquely characterised by the association of diffuse PVNH and progressive microcephaly. We describe a two-year-old boy born to consanguineous parents who presented with severe developmental delay, hypotonia, progressive microcephaly, and infantile-onset epileptic spasms with developmental regression. Brain MRI showed extensive bilateral PVNH associated with callosal hypoplasia and ventriculomegaly. EEG revealed dysmature background activity with multifocal epileptiform discharges and runs of asynchronous fast activity during sleep. Genetic testing identified a novel homozygous nonsense variant in ARFGEF2. The clinical course was characterised by drug-resistant epilepsy and multisystemic involvement, including feeding difficulties and recurrent respiratory infections. To contextualise this case, we performed a comprehensive review of previously reported patients, further delineating the clinical, neuroradiological, and electroclinical spectrum of ARFGEF2-related disorder. This case highlights progressive microcephaly as a key distinguishing feature of ARFGEF2-related PVNH and underscores the importance of early genetic diagnosis to guide targeted surveillance for extra-CNS complications and multidisciplinary care. Full article

Extremity vascular malformations in children and adolescents are congenital vascular developmental abnormalities that often present to pediatric orthopedic surgeons with pain, swelling, restricted motion, contracture, gait disturbance, limb asymmetry, and growth-related deformity rather than with an obvious vascular phenotype. The orthopedic importance of these lesions lies less in surface appearance than in their potential to affect muscle balance, joint integrity, osseous development, and peri-procedural safety. This review translates contemporary vascular anomaly classification and multidisciplinary management pathways into a practical orthopedic framework for diagnosis, referral, and longitudinal limb management. The most useful first step is to distinguish low-flow from high-flow lesions and then define lesion depth, periarticular or osseous involvement, coagulopathy risk, and syndromic overgrowth phenotype. Ultrasound is usually the first-line imaging modality for flow characterization, whereas magnetic resonance imaging is the cornerstone for defining extent and planning treatment. Plain radiographs remain highly relevant for identifying phleboliths, osseous remodeling, arthropathy, contracture-related deformity, and limb-length discrepancy. Venous malformations generally warrant pathway-based coagulation assessment, especially D-dimer and fibrinogen, because localized intravascular coagulopathy has direct implications for intervention and surgery. Arteriovenous malformations are best managed within specialist multidisciplinary teams. Fibro-adipose vascular anomaly and syndromic overgrowth phenotypes warrant particular attention because they frequently drive pain, contracture, and progressive limb imbalance. Outcome assessment in this field should extend beyond lesion size and incorporate pain, function, quality of life, and growth-related consequences. For pediatric orthopedic surgeons, management should move from late deformity correction toward early classification, early referral, longitudinal surveillance of joint and growth-related complications, and careful integration of local, surgical, and systemic therapies. Full article

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous combustion-derived contaminants that represent a significant cross-cutting threat to human, animal, and environmental health. Viewed through an explicit One Health lens, this review shows how the shared combustion sources, evolutionarily conserved toxicological mechanisms, and food-web linkages connecting environmental contamination to wildlife and human exposure justify an integrated, cross-domain approach to PAH risk assessment and management. PAHs are generated predominantly through incomplete combustion of organic materials and are globally distributed through atmospheric transport, aquatic runoff, and food-web transfer, persisting in soils and sediments for decades. The present review synthesizes current knowledge on PAHs through an explicit One Health lens, examining shared sources, environmental fate, and convergent health effects across species and health domains, while also highlighting the need to move beyond the classical US EPA priority PAHs to include high-molecular-weight PAHs (>302 Da), alkylated homologues, and transformation products such as oxy- and nitro-PAHs. Common pathways such as dietary intake of grilled and smoked foods, inhalation of contaminated air, and occupational exposure create parallel toxicological burdens in both human and wildlife populations, particularly through genotoxic mechanisms mediated by aryl hydrocarbon receptor (AhR) activation and CYP1A1/CYP1B1-catalyzed bioactivation to reactive diol epoxides. The resulting DNA adduct formation links environmental PAH exposure to carcinogenicity, reproductive toxicity, immunosuppression, and developmental impairment across vertebrate species with remarkable mechanistic consistency. Wildlife, especially fish, marine mammals, and seabirds, serve as critical sentinels for environmental PAH contamination, while simultaneously facing direct health impacts on immune function, reproduction, and population viability. Vulnerable human populations, including children, subsistence communities, occupational workers, and residents near combustion-intensive industries, bear disproportionate burdens reflecting underlying environmental justice concerns. Integrated intervention strategies encompassing source control, dietary exposure reduction, site remediation, and coordinated biomonitoring are urgently needed. By incorporating emerging PAH classes with distinct persistence, trophic behavior, and toxicological potency, the One Health paradigm provides a more comprehensive conceptual framework for modern environmental surveillance, food safety, and integrated risk assessment, recognizing that the health of terrestrial and aquatic ecosystems is inseparable from that of the animals and humans within them. Full article

Neurodegenerative diseases (NDDs) in children represent a heterogeneous group of rare but collectively significant disorders characterized by progressive neurological decline, developmental regression, and substantial morbidity and mortality. Unlike adult-onset neurodegeneration, pediatric conditions are predominantly genetic and frequently arise from defects in fundamental cellular pathways, including lysosomal degradation, mitochondrial oxidative phosphorylation, peroxisomal lipid metabolism, and myelin maintenance. This comprehensive review synthesizes current knowledge regarding the epidemiology, molecular classification, pathophysiology, and emerging therapeutic strategies of major pediatric neurodegenerative disorders. Epidemiological data indicate a “rare-but-many” landscape, where individually uncommon diseases collectively impose a measurable population burden. Mechanistically, disease progression reflects converging processes such as toxic substrate accumulation, impaired autophagy–lysosome flux, mitochondrial bioenergetic failure, oxidative stress, neuroinflammation, and glial dysfunction. Representative groups discussed include lysosomal storage disorders, leukodystrophies, mitochondrial encephalopathies, peroxisomal disorders, and other monogenic neurodegenerative syndromes. Advances in next-generation sequencing, metabolic profiling, and neuroimaging have substantially improved diagnostic accuracy and enabled earlier detection, including through newborn screening programs. Therapeutic paradigms are shifting from primarily supportive care toward mechanism-based interventions, including enzyme replacement therapy, hematopoietic stem cell transplantation, substrate reduction strategies, and gene therapy approaches. Early molecular diagnosis is increasingly recognized as critical for optimizing outcomes, particularly in disorders amenable to presymptomatic intervention. Continued integration of genomic medicine, standardized epidemiologic surveillance, and translational research will be essential to refine disease classification, improve prognostication, and expand access to targeted therapies. Collectively, pediatric neurodegenerative diseases exemplify the intersection of developmental neurobiology and inherited metabolic dysfunction, underscoring the need for multidisciplinary, precision-based clinical strategies. Full article

Mulibrey nanism is a rare autosomal recessive multisystem disorder caused by biallelic loss of function variants in TRIM37 encoding a peroxisomal E3 ubiquitin ligase. Initially described in Finland, where it remains most prevalent due to a founder mutation, the condition is now recognized worldwide and is characterized by severe prenatal-onset growth failure, distinctive craniofacial features, radiological abnormalities, ocular findings, and hepatopathy. Although its clinical spectrum extends far beyond these core manifestations, the major determinant of morbidity and mortality is progressive cardiovascular disease, including constrictive pericarditis and restrictive cardiomyopathy. Additional features include metabolic dysfunction such as insulin resistance and type 2 diabetes, gonadal insufficiency, skeletal abnormalities including fibrous dysplasia, and an increased risk of benign and malignant tumours. The clinical course evolves across the lifespan from early growth and developmental abnormalities to progressive multisystem disease in adolescence and adulthood. Recent advances have expanded understanding of TRIM37 function, linking it to mTORC1 TFEB signalling autophagy, centrosome integrity, extracellular matrix regulation, and immune cell function, providing mechanistic insights into tumour predisposition, skeletal pathology, and immune dysregulation. Management remains supportive and requires multidisciplinary care with emphasis on early recognition and treatment of cardiac disease, metabolic complications, and malignancy risk. Prognosis is variable but improves with early diagnosis and appropriate surveillance. This review summarises the clinical spectrum molecular mechanisms and current management of Mulibrey nanism and highlights priorities for future research. Full article

This study examines how UNHCR’s administrative category of the “person of concern” functions as a governance mechanism in refugee education policy, stripping refugees of political agency and positioning them as subjects of institutional control rather than rights-bearing actors. Employing Fairclough’s three-dimensional Critical Discourse Analysis alongside Quijano’s coloniality of power, the paper analyzes five key policy documents: four UNHCR education strategies spanning 2010 to 2020 and the World Bank’s INSPIRE Guide to Refugee Inclusion in National Education Systems (2025). The analysis identifies four dominant discursive themes: education as a mechanism of control, dehumanization and the passive subject, the neoliberalization of refugee education, and colonial legacies in knowledge production. The INSPIRE Guide is examined as a paradigmatic text crystallizing the shift from humanitarian parallel systems to developmental inclusion, revealing how the language of inclusion, efficiency, and sustainability reconfigures refugee education as economic governance while leaving the “person of concern” category uninterrogated. The study argues that UNHCR education policies reproduce colonial governance patterns in which education actively produces particular refugee subjects who can be governed, surveilled, and integrated into host-state frameworks on institutional terms. Findings challenge the assumed neutrality of humanitarian education frameworks and call for decolonial approaches centering refugee agency, epistemic sovereignty, and self-determined educational futures. Full article

Haplosporidium edule is a haplosporidian parasite originally described in the common edible cockle (Cerastoderma edule) along the European Atlantic coast. In this study, we report the first detection of H. edule in the olive-green cockle (Cerastoderma glaucum) from the northern Adriatic Sea, representing both a novel host record and a new geographic occurrence. During a cross-sectional study conducted in May 2019, 90 C. glaucum specimens were collected from three lagoon sites in northeastern Italy. Histological examination of soft tissues revealed haplosporidian developmental stages, including plasmodia, sporoblasts and mature spores, within connective tissues of the mantle, digestive gland, gills and between gonadal tubules in eight individuals from the Goro Lagoon. Molecular characterization based on a fragment of the small subunit ribosomal DNA showed high similarity with the previously published H. edule sequence. Host identification was confirmed through cytochrome c oxidase subunit I barcoding together with morphological and histological analyses. These findings indicate that H. edule has a broader host range than previously recognized. Although prevalence was relatively low, the detection of this parasite in a new host species and geographic area highlights the importance of continued surveillance, particularly in the context of climate change, shellfish translocations and the expansion of aquaculture activities. Full article

Ticks are vectors of pathogens affecting wildlife, livestock, and humans. Knowledge of their abundance, species composition, and ecological drivers is essential for an understanding of tick-borne disease ecology. In this study, four natural sites in Sicily (southern Italy) were selected, and 39 sampling events from April 2024 to August 2025 yielded 1200 ticks: 407 larvae, 474 nymphs, and 319 adults. Five genera were identified (Dermacentor, Haemaphysalis, Rhipicephalus, Ixodes, and Hyalomma); Rhipicephalus bursa was the most abundant species, followed by Haemaphysalis punctata. Most ticks were collected in spring–summer, except at one site where abundance peaked in autumn–winter. A significant association was found between site and season (p < 0.0001), but tick abundance per sampling event did not differ among sites (p = 0.431) or seasons (p = 0.769). No significant correlations emerged between tick abundance and environmental variants. However, significant associations were detected between site and sex (p < 0.0001), site and developmental stage (p < 0.0001), and species and developmental stage (p < 0.0001). Sites exclusively hosting wild boar showed higher species richness. These findings underscore the ecological complexity of tick populations in Mediterranean protected areas and provide baseline data useful for integrated tick surveillance and wildlife health management. Full article

Sex determination in honey bees (Apis mellifera) is controlled by the complementary sex determiner (csd) gene, which directs female- or male-specific splicing of the downstream feminizer (fem) transcript. Previous studies have reported contradictory data on the expression of fem transcripts in both sexes, but no rigorous quantitative analysis across developmental stages had been performed. Here, we optimized Real-Time PCR conditions to reliably detect and quantify both female-specific (fem^F) and male-specific (fem^M) transcripts, addressing challenges posed by AT-rich sequences, repeated regions, and cDNA instability. Using these methods, we analyzed transcript levels in eggs, larvae, and pupae of both sexes. Our results show that fem^F is highly specific for females, with approximately 100-fold higher expression in females than in males, whereas fem^M is less sex-specific, with only ~10-fold higher expression in males even at early developmental stages. Notably, fem^F transcripts are detectable in males, and fem^M expression increases in females during later pupal stages. Quantitative comparison indicates that fem^M expression in males is similar to fem^F expression in females, indicating that despite the presence of the premature stop codon in the male transcript, this transcript is not degraded through the mRNA surveillance mechanism. Our study provides a framework for evaluating fem transcript dynamics and has important implications for interpreting sex-determination mechanisms in honey bees. Full article

Objectives: To access the effects of febrile seizures from coexisting neurodevelopmental conditions that are commonly associated with autism spectrum disorder. We examined whether febrile seizures are independently associated with ASD after considering neurodevelopmental comorbidities and seizure-related clinical characteristics. Methods: We conducted a nationwide population-based matched cohort study using Taiwan’s National Health Insurance Research Database. The study included 948 children with FS and 3804 age- and sex-matched controls without FS. Participants were followed longitudinally for incident ASD. Associations were evaluated using Cox proportional hazards models with additional analyses restricted to the FS cohort. Neurodevelopmental comorbidities assessed included attention-deficit/hyperactivity disorder (ADHD), epilepsy, and Tourette syndrome/tic disorder. Results: Among 4752 children followed for more than 10 years, 43 (0.9%) developed ASD. FS were not independently associated with ASD in adjusted Cox regression models. In contrast, ADHD, epilepsy, and Tourette syndrome/tic disorder were strongly and consistently associated with ASD across analytic models. Conclusions: Febrile seizures were not independently associated with autism spectrum disorder. Instead, ASD risk was largely explained by coexisting neurodevelopmental comorbidities, consistent with a shared neurodevelopmental susceptibility framework. These findings suggest that developmental surveillance should prioritize children with neurodevelopmental disorders rather than those with febrile seizures alone. Full article

Background: Congenital scoliosis (CS) associated with multiple vertebral anomalies (MVAs) represents a biologically dynamic deformity in which cumulative segmental asymmetry, residual growth potential, and mechanobiological modulation interact to drive progression. Unlike isolated congenital lesions, MVAs exhibit growth-dependent and configuration-specific behavior, complicating risk stratification and timing of intervention. Despite extensive literature on congenital deformities, an integrated growth-oriented decision framework for this subgroup remains lacking. Methods: This narrative review synthesizes embryological, biomechanical, and clinical evidence related to vertebral growth potential, anomaly configuration, progression patterns, and age-dependent treatment strategies in CS with MVAs. A structured literature search of major databases was performed, and findings were analyzed thematically to propose a biologically grounded growth-based decision framework. Results: Across the literature, three interdependent determinants of progression consistently emerge: anomaly configuration, residual segmental growth capacity, and mechanobiological amplification during growth. High-risk configurations—particularly mixed formation–segmentation defects and fully segmented hemivertebrae with contralateral growth arrest—demonstrate rapid and often non-linear progression. Thoracic involvement further modifies clinical urgency due to its impact on pulmonary development. Integration of developmental biology and mechanobiological principles supports a structured, growth-informed approach to surveillance and intervention timing. Conclusions: MVAs should be conceptualized as dynamic growth systems rather than static structural defects. A shift from angle-driven to growth-informed decision-making may enhance early identification of high-risk patterns while minimizing unnecessary premature fusion in lower-risk cases. Adoption of a structured growth-based framework provides a biologically coherent foundation for individualized management and long-term optimization of spinal and thoracic development. Full article

This study aimed primarily to evaluate the performance of two Conformité Européenne—In Vitro Diagnostic (CE-IVD) multiplex real-time PCR (rt-PCR) assays for the molecular identification of tick-borne pathogens (TBPs) of human interest on ticks removed from human skin and collected through a citizen science-based approach. As a secondary objective, the aggregated results were used to describe tick species distribution, developmental stages, and seasonal TBP circulation in 2024 in the considered area. The comparison was conducted on 116 tick samples collected in 2024 voluntarily delivered to a hospital in northeastern Italy. Detected TBPs were further confirmed with in-house-validated PCR methods and, where applicable, resolved to the species level. Clinically relevant pathogen species were identified as single infections or coinfections. Overall, 33.6% of tick samples tested positive for at least one TBP, and 6.9% showed coinfections. Kit B exhibited a higher detection rate for Borrelia spp. and Rickettsia spp. targets, partly reflecting its broader diagnostic specificity, while statistically significant differences in cycle threshold values were observed for Anaplasma phagocytophilum detection. The most frequently involved ticks were Ixodes ricinus nymphs, and the most represented area was Verona province. Late spring and early summer were identified as the periods with the highest tick conferment and pathogen diversity. Overall, the results support the use of multiplex real-time PCR commercial kits combined with citizen science-based tick collection as an effective approach for both diagnostic screening and regional surveillance of circulating ticks and TBPs. Full article

Three-dimensional (3D) bioprinting provides new options for airway reconstruction by enabling the fabrication of customizable, biodegradable scaffolds designed to support in situ tissue regeneration. Building on our established large-animal platform, in which two cm bioprinted tracheal grafts combined with refined surgical techniques and adjunctive laser intervention have achieved long-term survival exceeding three months, the present study aims to explore long-segment (≥four cm) tracheal transplantation. We evaluated the fabrication feasibility and regeneration patterns of extrusion-based 3D bioprinted polycaprolactone (PCL) tracheal grafts in a porcine model. The grafts were implanted via end-to-end anastomosis with adjunctive mechanical stabilization and followed by serial bronchoscopic surveillance, gross examination, and histological analysis. The two cm PCL tracheal grafts achieved reproducible survival exceeding three months when combined with refined surgical techniques, structured postoperative airway management, and optimized wound coverage. Histological analysis revealed multi-lineage tissue formation—including cartilage, muscle, glands, and epithelium—was observed. Cartilage regeneration followed a staged maturation process, compared to epithelial regeneration, although continuous by 12 weeks, remained developmentally immature. A single long-segment transplantation was explored in a single preliminary case, providing an initial technical observation of feasibility; however, definitive conclusions regarding long-term survival or regeneration cannot be drawn. These findings further characterize regenerative responses in a large-animal model and highlight critical translational barriers—fabrication constraints, airway biomechanics, and delayed epithelial maturation—that require systematic investigation before long-segment tracheal reconstruction can advance toward clinical application. Full article

Wilms tumor (WT) is the most common malignant renal tumor in childhood and represents one of the major success stories of pediatric oncology, with very good survival achieved through risk-adapted multimodal therapy. Nevertheless, a subset of patients—particularly those with diffuse anaplasia, blastemal-type tumors persisting after chemotherapy, or relapsed disease—continues to experience poor outcomes and significant long-term treatment-related morbidity. These challenges highlight the need for novel therapeutic strategies beyond conventional cytotoxic approaches. Growing evidence indicates that WT is characterized by a complex and distinctive tumor microenvironment (TME) shaped by its developmental origin and triphasic histology. Immune cell infiltration, inflammatory mediators, and immune checkpoint pathways interact differently with blastemal, epithelial, and stromal tumor components, generating heterogeneous immune surveillance and escape mechanisms. In particular, tumor-associated macrophages (TAMs), functionally impaired natural killer (NK) cells, and immunosuppressive stromal elements play a central role in shaping an immune milieu that may limit the efficacy of immune-based therapies. Although immunotherapy has changed the management of several adult malignancies and some pediatric cancers, its translation to WT has so far been limited, with modest results in unselected patient populations. Recent immunogenomic and proteogenomic studies, however, suggest the existence of biologically distinct WT subsets with different immune features and potential susceptibility to targeted immunotherapeutic approaches. This narrative review integrates pathological, immunological, and clinical perspectives to summarize current knowledge on the WT immune microenvironment, mechanisms of tumor immune evasion, and emerging immunotherapeutic strategies. By providing a unified framework, it aims at supporting a multidisciplinary approach for the rational development of future immune-based and combination therapies tailored to specific WT subgroups. Full article

Fetal growth restriction (FGR), a condition in which the fetus fails to achieve its growth and developmental potential, affects 5% to 10% of pregnancies and is associated with high rates of perinatal morbidity and mortality. There is currently insufficient high-quality evidence to define the optimal approach for diagnosing fetal growth restriction. In 2016, with the aim of standardizing clinical practice and enabling comparability across scientific studies, an expert opinion-based consensus was published. This document proposed unified terminology and clear diagnostic criteria for early- and late-onset fetal growth restriction (FGR). Because no effective treatment is available, careful assessment of fetal well-being and appropriate timing of delivery are the main tools for managing these fetuses. This decision should be based on gestational age and the severity of abnormalities identified on fetal surveillance tests, balancing the risks of prematurity against the risks of severe permanent sequelae or fetal death. The objective of this update is to analyze the most recent evidence on when and how to deliver pregnancies complicated by fetal growth restriction, emphasizing that specific abnormalities on fetal surveillance examinations warrant delivery at different gestational ages. To this end, a literature search of the PubMed/Medline and Latin America and the Caribbean Literature on Health Sciences (LILACS) databases was conducted using the terms fetal growth restriction, management, and delivery over the past ten years. Results were grouped into gestational age at delivery, mode of delivery, and methods of labor induction. The main fetal surveillance abnormalities prompting delivery in each gestational-age range were discussed, leading to the development of management flowcharts. Despite the lack of consensus in the literature and the limited number of randomized clinical trials guiding clinical decisions in FGR, the available evidence was summarized to assist clinicians in managing pregnancies complicated by FGR. It should be emphasized that there are few randomized clinical trials to guide management decisions in FGR. Full article