Search Results (260)

The increasing demand for rapid, sensitive, and eco-friendly methods for the detection of trace heavy metals in environmental samples, attributed to their serious threats to health and the environment, has spurred considerable interest in the development of sustainable sensor materials. Toxic metal ions, namely, lead (Pb²⁺), cadmium (Cd²⁺), mercury (Hg²⁺), arsenic (As³⁺), and chromium, are potential hazards due to their non-biodegradable nature with high toxicity, even at trace levels. Acute health complications, including neurological, renal, and developmental disorders, arise upon exposure to such metal ions. To monitor and mitigate these toxic exposures, sensitive detection techniques are essential. Pre-existing conventional detection methods, such as atomic absorption spectroscopy (AAS) and inductively coupled plasma-mass spectrometry (ICP-MS), involve expensive instrumentation, skilled operators, and complex sample preparation. Electrochemical sensing, which is simple, portable, and eco-friendly, is foreseen as a potential alternative to the above conventional methods. Carbon-based nanomaterials play a crucial role in electrochemical sensors due to their high conductivity, stability, and the presence of surface functional groups. Biochar (BC), a carbon-rich product, has emerged as a promising electrode material for electrochemical sensing due to its high surface area, sustainability, tunable porosity, surface rich in functional groups, eco-friendliness, and negligible environmental footprint. Nevertheless, broad-spectrum studies on the use of biochar in electrochemical sensors remain narrow. This review focuses on the recent advancements in the development of biochar-based electrochemical sensors for the detection of toxic heavy metals such as Pb²⁺, Cd²⁺, and Hg²⁺ and the simultaneous detection of multiple ions, with special emphasis on BC synthesis routes, surface modification methodologies, electrode fabrication techniques, and electroanalytical performance. Finally, current challenges and future perspectives for integrating BC into next-generation sensor platforms are outlined. Full article

Objectives: The primary objective of this study was to determine whether motor disorders are significantly more prevalent in children with Autism Spectrum Disorder (ASD) without co-occurring genetic or neurological conditions compared to neurotypical children. Another aim was to explore the applicability of the MABC-2 test for assessing motor skills in a Polish cohort of children with ASD. Additionally, this study sought to develop a basic framework for motor skill assessment in children with autism. Methods: This study included 166 Caucasian children, both sexes, aged 5–12 years, without intellectual disability (IQ ≥ 70), without concomitant genetic or neurological disorders, particularly epilepsy or cerebral palsy. The study group consisted of children with ASD (n = 71), and the control group consisted of neurotypical children (n = 95). The participants were assessed with the Movement Assessment Battery for Children–second edition (MABC-2), MABC-2 checklist and the Developmental Coordination Disorder Questionnaire (DCDQ), used as a reference point. Results: The children with ASD obtained significantly lower MABC-2 test results in all subtests in comparison with the control group. The children with suspected or diagnosed coordination disorders were characterized by a significantly greater number of co-occurring non-motor factors than the other participants of this study. MABC-2 test showed greater consistency with DCDQ than with the MABC-2 questionnaire. Conclusions: Children with ASD present a lower level of manual dexterity and balance and greater difficulties in performing tasks, including throwing and catching, in comparison with neurotypical children. The MABC-2 test with the MABC-2 checklist and DCDQ questionnaire constitute a complementary diagnostic tool. Full article

Background: Butylated hydroxyanisole (BHA) has been extensively used in several commercial industries as a preservative. It causes severe cellular and neurological damage affecting the developing fetus and might induce attention deficit hyperactivity disorder (ADHD). Methods: Zebrafish embryos were subjected to five distinct doses of BHA—0.5, 1, 2, 4, and 8 ppb up to 96 h post fertilization (hpf). Hatching rate, heart rate, and body malformations were assessed at 48 hpf, 72 hpf, and 48–96 hpf, respectively. After exposure, apoptotic activity, neurobehavioral evaluation, neurotransmitter assay, and antioxidant activity were assessed at 96 hpf. At 120 hpf, the expression of genes DRD4, COMT, 5-HTR1aa, and BDNF was evaluated by real-time PCR. Results: BHA exposure showed a delay in the hatching rate and a decrease in the heart rate of the embryo when compared with the control. Larvae exhibited developmental deformities such as bent spine, yolk sac, and pericardial edema. A higher density of apoptotic cells was observed in BHA-exposed larvae at 96 hpf. There was a decline in catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and superoxide dismutase (SOD) activity, indicating oxidative stress. There was a significant decrease in Acetylcholinesterase (AChE) activity and serotonin levels with an increase in concentration of BHA, leading to a dose-responsive increase in anxiety and impairment in memory. A significant decrease in gene expression was also observed for DRD4, COMT, 5-HTR1aa, and BDNF. Conclusions: Even at lower concentrations of BHA, zebrafish embryos suffered from developmental toxicity, anxiety, and impaired memory due to a decrease in AChE activity and serotonin levels and altered the expression of the mentioned genes. Full article

The use of gait analysis to differentiate among paediatric populations with neurological and developmental conditions such as idiopathic toe walking (ITW), cerebral palsy (CP), and hereditary spastic paraplegia (HSP) remains challenging due to the insufficient precision of current diagnostic approaches, leading in some cases to misdiagnosis. Existing methods often isolate the analysis of gait variables, overlooking the whole complexity of biomechanical patterns and variations in motor control strategies. While previous studies have explored the use of statistical physics principles for the analysis of impaired gait patterns, gaps remain in integrating both kinematic and kinetic information or benchmarking these approaches against Deep Learning models. This study evaluates the robustness of statistical physics metrics in differentiating between normal and abnormal gait patterns and quantifies how the data source affects model performance. The analysis was conducted using gait data sets from two research institutions in Madrid and Dublin, with a total of 81 children with ITW, 300 with CP, 20 with HSP, and 127 typically developing children as controls. From each kinematic and kinetic time series, Shannon’s entropy, permutation entropy, weighted permutation entropy, and time irreversibility metrics were derived and used with Random Forest models. The classification accuracy of these features was compared to a ResNet Deep Learning model. Further analyses explored the effects of inter-laboratory comparisons and the spatiotemporal resolution of time series on classification performance and evaluated the impact of age and walking speed with linear mixed models. The results revealed that statistical physics metrics were able to differentiate among impaired gait patterns, achieving classification scores comparable to ResNet. The effects of walking speed and age on gait predictability and temporal organisation were observed as disease-specific patterns. However, performance differences across laboratories limit the generalisation of the trained models. These findings highlight the value of statistical physics metrics in the classification of children with different toe walking conditions and point towards the need of multimetric integration to improve diagnostic accuracy and gain a more comprehensive understanding of gait disorders. Full article

Background/Objectives: Neurodevelopmental disorders (NDDs) represent a clinically diverse group of conditions that affect brain development, often leading to varying degrees of functional impairment. Many NDDs, particularly syndromic forms, are caused by genetic mutations affecting critical cellular pathways. Ribosomopathies, a subgroup of NDDs, are linked to defects in ribosomal function, including those involving the synthesis of diphthamide, a post-translational modification of translation elongation factor 2 (eEF2). Loss-of-function (LoF) mutations in genes involved in diphthamide biosynthesis, such as DPH1, DPH2, and DPH5, result in developmental delay (DD), intellectual disability (ID), and multisystemic abnormalities. DPH5-related diphthamide deficiency syndrome has recently been reported as an ultrarare disorder linked to LoF mutations in DPH5, encoding a methyltransferase required for diphthamide synthesis. Methods: Clinical, neurological, and dysmorphological evaluations were performed by a multidisciplinary team. Brain MRI was acquired on a 3T scanner. Craniofacial abnormalities were assessed using the GestaltMatcher phenotyping tool. Whole exome sequencing (WES) was conducted on leukocyte-derived DNA with a trio-based approach. Bioinformatic analyses included variant annotation, filtering, and pathogenicity prediction using established databases and tools. Results: The affected subject carried a previously reported missense change, p.His260Arg, suggesting the occurrence of genotype–phenotype correlations and a hypomorphic behavior of the variant, likely explaining the overall milder phenotype compared to the previously reported patients with DPH5-related diphthamide deficiency syndrome. Conclusions: Overall, the co-occurrence of short stature, relative macrocephaly, congenital heart defects, variable DD/ID, minor skeletal and ectodermal features, and consistent craniofacial features suggests a differential diagnosis with Noonan syndrome and related phenotypes. Full article

Circular RNAs (circRNAs) are single-stranded noncoding RNAs with a covalently closed loop structure. They are known for their stability, abundance, and highly conserved nature. Their expression is often specific to tissues or developmental stages. They interact with microRNAs (miRNAs) and RNA-binding proteins (RBPs) and they undergo N⁶-methyladenosine (m⁶A) modifications, further affecting gene transcription and translation. Increasing evidence over the past decades has revealed that dysregulated circRNA expression is associated with various neurological disorders, particularly the glioma, one of the most malignant tumors with a poor prognosis. Due to the presence of the blood–brain barrier (BBB) and drug resistance, conventional therapeutic approaches have shown limited efficacy. Recently, increasing attention has been directed toward precisely targeted therapies, with circRNAs emerging as promising molecules for cancer treatment. Studies indicate that circRNAs play a key role in glioma proliferation and metastasis. Substantial evidence indicates that exosomes can package circRNAs and facilitate their transport across the BBB into brain tissue, highlighting the potential of circRNAs as therapeutic targets for glioma. This review summarizes circRNAs’ functional mechanisms, clinical application relevance, and current limitations. It offers future research directions in this evolving field, aiming to encourage further research on circRNAs’ therapeutic applications and contribute to the development of novel glioma-treatment strategies. Full article

Autism spectrum disorder (ASD) is a complex neurological and developmental condition that occurs in approximately 1 in 100 children. ASD is a lifelong condition defined by difficulties with social communication, restricted interests, and repetitive behaviors, among other symptoms. Currently, we understand that there is no cure and the disorder can only be managed with occupational therapy alongside limited medical treatments. Reasons underlying the pathogenesis of ASD are still not well understood, but recent studies point to the influence of epigenetic dysregulation in ASD development, which opens up avenues to novel diagnosis and treatment options. In this review, we summarize recent findings and emerging therapeutics for ASD, with a focus on implications of epigenetic regulatory pathways and factors. We expound the implications of these findings to enable preventive measurements for mothers to reduce the impact of ASD at birth, non-invasive diagnostic tests for early detection, and personalized medicine management. Finally, we discuss several critical issues to be addressed and future directions of this important research field. Full article

Background/Objectives: Developmental Topographical Disorientation (DTD) refers to a condition in which individuals report getting lost in very familiar surroundings, since childhood, with no other cognitive complaints, and no brain injuries or neurological disorders. While the cognitive and neurological mechanisms underlying DTD are being investigated, to date, there is no tool available to the public and health practitioners for identifying this lifelong condition. Methods: Here, we used a decade of data (N = 3794) collected in healthy and DTD individuals to produce a short and reliable measure of self-reported sense of direction that could point to the presence of DTD. Results: We adopted a measure of internal consistency (Cronbach’s alpha) and identified four items of the well-known Santa Barbara Sense of Direction (SBSOD) Scale that retain its original strong internal consistency. These four items remain sensitive to the well-known effects of sex on spatial orientation and, importantly, to the presence of DTD, while maintaining the same pattern of association with a cognitive battery of computerized tasks measuring different spatial abilities. Conclusions: This four-item measure could be of practical use to obtain a rapid assessment of an individual’s self-reported sense of direction and help to identify the presence of DTD in the general population. Full article

Rett syndrome (RTT) is a multisystem neurological disorder. Pathogenic changes in the MECP2 gene that codes for methyl-CpG-binding protein 2 (MeCP2) in RTT lead to a loss of previously established motor and cognitive skills. Unravelling the mechanisms of neurological regression in RTT is complex, due to multiple components of the neural epigenome being affected. Most evidence has primarily focused on deciphering the complexity of transcriptional machinery at the molecular level. Little attention has been paid to how epigenetic changes across the neural epigenome in RTT lead to neurological regression. In this narrative review, we examine how pathogenic changes in MECP2 can disrupt the balance of the RTT neural epigenome and lead to neurological regression. Environmental and genetic factors can disturb the balance of the neural epigenome in RTT, modifying the onset of neurological regression. Methylation changes across the RTT neural epigenome and the consequent genotoxic stress cause neurons to regress into a senescent state. These changes influence the brain as it matures and lead to the emergence of specific symptoms at different developmental periods. Future work could focus on epidrugs or epi-editing approaches that may theoretically help to restore the epigenetic imbalance and thereby minimise the impact of genotoxic stress on the RTT neural epigenome. Full article

This case study presents the long-term management of a 14-year-old male diagnosed with 18q deletion syndrome, also known as de Grouchy Syndrome, highlighting the challenges of treating rare chromosomal disorders in rural Romania. Background and Clinical Significance: 18q deletion syndrome, also known as de Grouchy syndrome, is a chromosomal disorder caused by the deletion of a part of the long arm of chromosome 18. This syndrome is seen in one out of 10,000 live births. The main features of the syndrome are short stature, hearing loss, hypotonia, mental retardation, endocrine disorders, and autoimmunity. Case Presentation: The patient’s condition was initially suspected at birth due to abnormal features and was later confirmed through genetic testing, revealing a 46,XY,del(18) karyotype. Key clinical features include craniofacial dysmorphism, delayed growth, congenital cardiac anomalies, developmental delay, severe neurological impairment, and multiple comorbidities such as endocrine dysfunction, dental anomalies, and orthopedic deformities. Despite early interventions such as cardiac surgery, the patient’s management has been challenged by limited access to specialized care. Conclusions: The case underscores the importance of timely genetic testing, early multidisciplinary care, and the role of family support in managing complex disorders. This report also addresses the gaps in healthcare accessibility in rural settings and emphasizes the need for improved infrastructure and genetic services. By comparing this case with the existing literature, the study explores the variability in clinical presentations of 18q deletion syndrome and advocates for more precise genetic testing to better understand its phenotypic spectrum. The patient’s ongoing challenges with medical and socio-economic factors emphasize the critical need for coordinated care and family support in managing rare genetic conditions. Full article

Cerebral malaria (CM) is a deadly complication of P. falciparum infection. Although adults with CM have a higher mortality rate, CM affects mostly children under the age of 5 years. Neurological symptoms and signs include impaired consciousness, coma, seizures, and increased intracranial hypertension. Upon survival of a CM episode, persistent neurologic deficits occur in a subset of surviving children. These sequelae include recurrent seizures, behavioral deficits, loss of developmental milestones, learning disabilities and attention deficit hyperactivity disorder, which can remain with the survivors. The underlying neuropathology of these post CM neurologic sequelae are unclear. Therefore, we probed the extensive neuronal damage that occurs in an experimental murine model of cerebral malaria (eCM), focusing on the hippocampus. In addition, we explored responses of neuro-progenitor cells (NPC’s) and potential repair mechanisms. We report here that Plasmodium infection causes extensive neuronal damage in the hippocampus, characterized by a loss of neuronal NeuN and double cortin (DCX) immunostaining in eCM mice. On day 6 of eCM we also observed increased neurofilament light chain staining, indicative of neuronal fragmentation, which was accompanied by an increase in neurofilament light chain in CSF but not seen in plasma. A concomitant increase in the influx of neuroprogenitor cells in eCM was observed, suggesting ongoing neuronal repair. Full article

Phenylketonuria (PKU) is a common inherited metabolic disorder characterised by impaired metabolism of the amino acid phenylalanine. The disease results from a mutation in the phenylalanine hydroxylase (PAH) enzyme, which converts phenylalanine (Phe) into tyrosine (Tyr). The absence or inactivity of this enzyme results in significantly elevated levels of Phe in the blood, which can lead to severe neurological conditions, including intellectual disability, epilepsy, and other developmental disorders. Since its discovery, animal models have played a crucial role for understanding the pathophysiology of PKU, as well as providing recognisable proof of targets and surveying new remedial specialists and in vivo medicines. In the present study, we conducted a comprehensive review of the experimental and non-experimental animal models employed for phenylketonuria and its associated complications. Full article

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a rising prevalence, driven by multifactorial genetic and environmental factors. Among the genetic contributors identified, SCN2A, a critical gene encoding the Nav1.2 sodium channel, has been implicated in ASD and other related neurological conditions. This systematic review aims to explore the relationship between SCN2A mutations and ASD phenotypes. Methods: This review systematically analyzed data from studies reporting SCN2A mutations in individuals diagnosed with ASD. The primary focus was on the characterization of mutation types, associated clinical features, and phenotypic variability. Results: The mutations identified were predominantly de novo missense mutations and were associated with a spectrum of neurological and developmental challenges, including seizures, intellectual disability, movement disorders, and repetitive behaviors. A notable finding was the significant phenotypic variability observed across individuals. Gender differences emerged, suggesting a potentially greater impact on females compared to trends typically seen in ASD genetic studies. Specific mutations, such as c.2919+4delT, and mosaicism were identified as novel contributors to the observed heterogeneity. Conclusions: The review highlights the clinical significance of SCN2A mutations in ASD and highlights their relevance in genetic counseling and the development of targeted therapies. Understanding the diverse genotype–phenotype correlations associated with SCN2A can drive progress in personalized medicine, paving the way for precision therapies tailored to individuals with SCN2A-related ASD. Full article

Epilepsy is a prevalent neurological condition, having a wide range of phenotypic traits, which complicate the diagnosis process. Next-generation sequencing (NGS) techniques have improved the diagnostics for unexplained epilepsies. Our goal was to evaluate the utility and impact of genetic testing in the clinical management of pediatric epilepsies. In addition, we aimed to identify clinical factors that could predict a genetic diagnosis. This was a retrospective study of 140 pediatric patients with epilepsy with or without other neurological conditions that underwent NGS testing (multigene panel, WES = whole exome sequencing and/or WGS = whole genome sequencing). A comparison between genetically diagnosed versus non-diagnosed children was performed based on different clinical features. Univariate and multivariate logistic regression analysis was performed to identify clinical predictors of a positive genetic diagnosis. Most children underwent gene panel testing, while 30 had exome sequencing and 3 had genome sequencing. The overall diagnostic yield of genetic testing was 28.6% (40/140) for more than 28 genes. The most frequently identified genes with causative variants were SCN1A (n = 4), SCN2A (n = 3), STXBP1 (n = 3), MECP2 (n = 2), KCNQ2 (n = 2), PRRT2 (n = 2), and NEXMIF (n = 2). Significant predictors from the logistic regression model were a younger age at seizure onset (p = 0.015), the presence of intellectual disability (p = 0.021), and facial dysmorphism (p = 0.049). A genetic diagnosis led to an impact on the choice or duration of medication in 85% (34/40) of the children, as well as the recommendation for screening of comorbidities or multidisciplinary referrals in 45% (18/40) of children. Epilepsy is a highly heterogeneous disorder, both genetically and phenotypically. Less than one third of patients had a genetic diagnosis identified using panels, exomes, and/or genomes. An early onset and syndromic features (including global developmental delay) were more likely to receive a diagnosis and benefit from optimized disease management. Full article

Fatigue is a common consequence of traumatic brain injury, neurological diseases or developmental disorders, and systemic inflammatory diseases, including autoimmune conditions that affect the brain. This condition is characterized by reduced endurance for cognitive tasks, diminished quality of life, and impaired work capacity. In addition to cognitive difficulties, individuals often experience disproportionately long recovery times after demanding tasks, emotional instability, stress sensitivity, sensory sensitivity, impaired ability to initiate activities, and sleep disturbances. Tension headaches frequently occur when the brain is excessively activated by mental activity. In this paper, we propose the term “Brain Fatigue Syndrome” (BFS) as a collective name for the symptoms closely associated with this pathological fatigue resulting from brain impact. BFS can be identified through interviews and measured using the self-assessment instrument, the Mental Fatigue Scale (MFS). We suggest potential underlying mechanisms at the cellular level for the BFS symptom complex, including astrocyte dysfunction with impaired glutamate signaling and glucose uptake, mitochondrial dysfunction, blood–brain barrier dysfunction, and the activation of microglia and mast cells. In conclusion, BFS suggests a general brain impact. The symptoms associated with BFS typically resolve when the injury or disease heals. However, in some individuals, BFS persists even after the injury or illness has ostensibly healed. Full article