Search Results (733)

Heavy metals (HMs) and rare earth elements (REEs) increasingly co-occur in environmental waste streams and soils, yet their comparative neurotoxic mechanisms and sublethal effects on invertebrate decomposers remain poorly understood. This study used black soldier fly larvae (BSFL, Hermetia illucens) to perform a comparative behavioral and transcriptomic assessment of 23 HMs and 16 REEs across two acute exposure concentrations. High-throughput video tracking and phenomic analysis showed HMs produced broader disruption than REEs, with low-concentration HMs inducing locomotor suppression, thigmotaxis, reduced fractal dimension and entropy, progressing to severe motor inhibition and rigid low-entropy states. In contrast, REEs showed a biphasic profile, shifting from selective locomotor suppression with preserved organization at low concentrations to hyperactive, fragmented, high-entropy movement with increased thigmotaxis at high concentrations. PCA and hierarchical clustering integrated endpoints into four neurobehavioral fingerprints segregating metal class and concentration, with partial overlap of high-concentration REEs with HMs along a shared high-toxicity axis. Transcriptomic profiling showed that cobalt as a representative HM activated DNA damage and cell-cycle pathways, perturbed energy signaling, and suppressed neuroactive ligand–receptor interaction, whereas samarium as a representative REE downregulated xenobiotic metabolism, oxidative phosphorylation, glutathione metabolism, and synaptic vesicle cycling. These findings demonstrate distinct concentration-dependent neurotoxic modes of action for HMs and REEs and establish BSFL behavioral phenomics integrated with transcriptomics as a mechanistically informative platform for ecological risk assessment in contaminated waste systems. Full article

Objectives: This systematic review synthesized the existing literature to evaluate the associations between maternal Selenium (Se) exposure during pregnancy and neonatal outcomes, specifically focusing on parameters of mortality, morbidity, and neurobehavioral development. Methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception through December 2025. For quality appraisal, Cochrane RoB2 and the National Heart, Lung, and Blood Institute of the National Institutes of Health tools for observational studies were applied. Results were qualitatively synthesized. Results: Screening of 2743 unique records and 473 full-text articles yielded 355 papers included in the overarching SeduP project, with 19 specific to this review. Synthesized evidence revealed a lack of consistent evidence of an association between maternal Se status and all-cause neonatal or perinatal mortality (n = 413, 4 studies), combined mortality/morbidity (n = 2753, 2 studies), or infectious-related morbidity (n = 928, 3 studies). Conversely, conflicting findings were observed regarding all-cause neonatal morbidity (n = 68, 2 studies) and neurobehavioral development (n = 1442, 4 studies), while a potentially inverse association was identified exclusively between Se levels and pulmonary-related neonatal morbidity (n = 611, 4 studies). Conclusions: Despite compelling preclinical biological plausibility, clinical data do not support a widespread protective effect of maternal Se status against adverse neonatal outcomes. The existing body of evidence is heavily constrained by moderate to very low quality, driven by small sample sizes, insufficient confounding adjustments, and suboptimal exposure assessment timing at delivery. While localized signals imply potential pulmonary protection alongside risks of excess toxicity, large-scale, standardized prospective cohorts are critically needed to generate clinically actionable data. Full article

Type 2 diabetes mellitus (T2DM) is a widely distributed dysmetabolic condition increasingly linked to neurocognitive decline, neuroinflammation, oxidative stress, and neuronal apoptosis. Chronic hyperglycemia and insulin resistance disrupt homeostasis in the central nervous system, contributing to neurodegenerative processes. This study evaluated the effects of semaglutide (SMG), a glucagon-like peptide-1 receptor agonist, on T2DM-associated neurobehavioral and biochemical alterations using a rat model. T2DM was induced by nicotinamide–streptozotocin, followed by oral administration of SMG at a dose of 1.44 mg/kg for one month. Cognitive function was evaluated using the elevated plus maze (EPM) and novel object recognition (NOR) paradigms. Fasting blood glucose and body weight were monitored throughout the experiment. Neuroinflammatory markers (COX-2, TNF-α, and IL-6), oxidative stress biomarkers (MDA, GSH, and catalase), and apoptosis-associated proteins (Caspase-3, Bax, and Bcl-2) were measured in brain tissue homogenates using ELISA. Diabetic rats exhibited marked cognitive deficits, hyperglycemia, increased neuroinflammatory markers, and altered apoptosis-related biomarkers, with reduced Bcl-2 expression. Treatment with SMG significantly improved learning and memory performance, fasting blood glucose, and body weight. At the molecular level, SMG treatment was associated with lower levels of MDA, TNF-α, Bax, IL-6, COX-2, and Caspase-3, together with higher levels of Bcl-2, catalase, and GSH compared with untreated diabetic rats. Overall, oral SMG treatment was associated with improved cognitive performance and metabolic control, accompanied by attenuation of diabetes-associated neuroinflammatory, oxidative stress, and apoptosis-related alterations in brain tissue. However, the present study was not designed to distinguish direct neuroprotective effects from changes secondary to improved metabolic control. Further studies are required to clarify the underlying mechanisms and determine the translational relevance of these findings. Full article

Smoking remains a leading preventable cause of death, and nicotine is the primary substance responsible for maintaining use of tobacco products. Preclinical rodent models have shown that neuroimmune signaling is dysregulated by nicotine self-administration (SA) within the nucleus accumbens core (NAcore). Microglia are the resident brain immune cell and prior studies have shown that they play an important role in nicotine-related behaviors. However, while transgenic mouse lines allow for specific evaluations of microglia to determine their role in neurobiology and behavior, there are fewer tools available for rats as a model species, thus limiting our ability to evaluate specific contributions of microglia to nicotine SA. A transgenic rat expressing Cre under the control of the CX3CR1 promoter bred on a Long–Evans (LE) background was recently developed, and here we show that NAcore microglia can be virally transduced with designer receptors exclusively activated by designer drugs (DREADDs) without neuronal expression. We further show that CX3CR1::ERT2 rats readily self-administer nicotine and display a characteristic extinction curve. Together, these validation studies lay the foundation for future use of this transgenic rat line to evaluate the specific contributions of microglia within the brain reward pathway to the neurobehavioral underpinnings of nicotine addiction. Full article

Microbiota, whether in the gut, skin, or other habitats, has a long history of co-evolution with the host, and plays vital physiological and pathological roles, such as mediating the metabolism, barrier function, immune balance, biological rhythm, and neurobehavior, as well as the occurrence and development of diseases [...] Full article

Background: Community-acquired pneumonia (CAP) remains a leading cause of pediatric morbidity and mortality worldwide, particularly in low-resource settings. Although antimicrobial therapy is the cornerstone of treatment, disease severity is often influenced not only by pathogen burden but also by dysregulated host inflammation. Systemic corticosteroids have therefore been investigated as adjunctive agents to reduce inflammation-mediated lung injury, but their role in children remains controversial. Methods: This narrative review summarizes current evidence on systemic corticosteroid use in pediatric pneumonia. The review focuses on biological mechanisms, clinical indications, patient selection, therapeutic regimens, timing and duration of therapy, clinical outcomes, and safety. Particular attention is given to severe CAP, Mycoplasma pneumoniae pneumonia, complicated pneumonia with parapneumonic effusion or empyema, viral pneumonia, wheezing-associated phenotypes, and immunocompromised children. Results: Available evidence suggests that corticosteroids may provide benefit in selected pediatric phenotypes characterized by severe inflammation, respiratory compromise, refractory disease, or airway hyperreactivity. Reported benefits include faster fever resolution, reduction in inflammatory markers, shorter hospital stay, more rapid clinical stabilization, and improved radiographic recovery, particularly in severe or refractory Mycoplasma pneumoniae pneumonia and selected complicated cases. However, findings are inconsistent, and treatment effects appear strongly dependent on etiology, disease severity, timing of administration, corticosteroid regimen, and patient phenotype. Routine use in uncomplicated CAP or unselected pediatric populations is not supported. Potential adverse effects include hyperglycemia, gastrointestinal and neurobehavioral symptoms, sleep disturbance, immunosuppression with an increased risk of secondary infection, delayed viral clearance in selected viral infections, and possible masking of inadequate anti-infective response or evolving complications. Conclusions: Current evidence supports a cautious, individualized, phenotype-driven approach to corticosteroid therapy in pediatric CAP. Well-designed pediatric randomized controlled trials are needed to define precise indications, optimal regimens, timing, and long-term safety. Full article

Background/Objectives: Synthetic cathinones are a rapidly evolving class of new psychoactive substances whose structural diversity complicates toxicological risk assessment. Methylenedioxy cathinones occupy a pharmacological space between MDMA-like entactogens and more dopaminergic stimulant cathinones, but their direct cardiac liabilities remain poorly characterized. This study aimed to compare the cardiotoxic and neurobehavioral profiles of methylone, butylone, pentylone and their N,N-dimethyl analogues, and to determine how alkyl-chain extension and terminal amine substitution shape functional toxicity. Methods: Wild-type short-fin zebrafish (Danio rerio) embryos were used as a multiparametric New Approach Methodology. Cardiac rhythmicity was assessed in 3 days post-fertilization embryos after acute exposure to methylone, butylone, pentylone, dimethylone, dibutylone, dipentylone, dihexylone and diheptylone by high-speed video microscopy and dynamic pixel-based analysis, focusing on atrial chronotropy and atrioventricular conduction. Basal locomotor activity was evaluated in 5 days post-fertilization eleutheroembryos over 120 min using automated video tracking. Results: Negative chronotropy increased with alkyl-chain extension, with the monoalkyl subset following the rank order methylone < butylone < pentylone. Among dialkyl analogues, dihexylone and, especially, diheptylone produced the strongest atrial-rate inhibition. AV conduction impairment was more heterogeneous but became prominent among higher-liability analogues, with diheptylone showing the lowest AV-block midpoint descriptor and complete lethality at 1000 µM. Locomotor profiling revealed predominantly hypoactive phenotypes, with sustained late-phase inhibition especially for dipentylone, dihexylone and diheptylone. Conclusions: Alkyl-chain extension and terminal amine substitution shaped cardiac and neurobehavioral toxicity in a structure-dependent manner. The zebrafish workflow provides a structure-oriented framework for prioritizing emerging methylenedioxy cathinones with comparatively higher functional cardiac liability. Full article

Background/Objectives: Antenatal corticosteroids (ACSs) are widely used to improve outcomes in preterm infants, but their effects in the context of fetal growth restriction (FGR) remain incompletely understood. This study investigated the impact of ACSs on pulmonary and neurodevelopmental outcomes using a rabbit mod (K.Z.el) of FGR. Methods: FGR was induced at a gestational age (GA) of 25 days (term 31.5 days) by partial uteroplacental vessel ligation (UPVL) in one uterine horn, with the contralateral horn serving as a control. Dams received intramuscular betamethasone (0.1 mg/kg) or saline 24 and 12 h before expected delivery. At GA 30 days, offspring were delivered by caesarean section and allocated to four groups for pulmonary function testing or neurobehavioral assessment on postnatal day 1, followed by histological analyses of the brain, lungs, and placenta. Results: ACSs improved respiratory mechanics, particularly static and dynamic compliance, in FGR offspring. PND 1 survival showed a concerning pattern, with numerically lower model-estimated survival in both ACS-exposed groups, although the only statistically significant adjusted comparison was between Control/NoACS and FGR/ACS offspring. Neurobehavioral testing showed lower neurosensory performance after ACS exposure within both control and FGR offspring. Lung morphometry and apoptosis were not significantly altered, while neuronal density and astrogliosis showed isolated regional differences. Placental histology showed a higher junctional zone proportion in untreated FGR placentas than in untreated controls. Conclusions: ACSs improved short-term respiratory mechanics without detectable alveolar structural benefit. The observed PND 1 survival pattern and lower neurobehavioral performance warrant cautious interpretation, and these animal findings should not be directly extrapolated to clinical ACS decision-making in FGR pregnancies. Full article

Background: Tryptophan (Trp) is critical to mothers and their conceptuses, and this amino acid is the precursor to serotonin (5-HT). 5-HT modulates placenta function and fetal neurodevelopment. It is not clear if the placenta directly synthesizes 5-HT or uses the serotonin transporter (SERT/Slc6a4) to accrue 5-HT from the dam. The hypothesis tested herein is that reduction in maternal Trp leads to reductions in maternal Trp, 5-HT, and 5-hydroxy-3-indoleacetic acid (5-HIAA, metabolite of serotonin) and reductions in these metabolites within the placenta and fetal brain of female and male conceptuses. Methods: Female mice were placed on a reduced tryptophan (Trp) diet (0.1%) or control diet (0.2%). Diets were provided for two weeks prior to breeding (periconception period) until conceptuses were collected at approximately 12.5 days post-coitus (dpc). Results: While no reductions in maternal Trp and 5-HT were observed, both metabolites were significantly reduced in the placenta and fetal brain of male and female conceptuses (p < 0.05). Female conceptuses were susceptible to reductions in maternal Trp with 549 and 29 transcripts altered in the female placenta and fetal brain, respectively, of reduced Trp dams compared to control dams. Transcriptomic changes, such as reduced expression in Slc6a4 and Slc6a19 (transporter for Trp), in placenta of female conceptuses correlated with reductions in Trp and 5-HT amounts. Conclusions: Findings might have clinical importance to pregnant women as they reveal even subtle reductions in one amino acid profoundly influence conceptus development and might lead to sexual disparity in risk for later diseases, including neurobehavioral disorders. Full article

Objectives and Background: Individuals with Phelan–McDermid Syndrome (PMS) present with a variety of symptoms, including a breadth of behavioral issues. Clinically assessing behavior in PMS remains challenging due to the overabundance of behavioral assessments and the lack of tools validated explicitly for use in individuals with intellectual disability (ID) and neurodevelopmental disorders. This review sought to suggest which assessment tools would best clinically assess behavior in individuals with PMS. Methods: Validated behavioral assessment tools were identified using a systematic search of the literature, and relevant data for each assessment were extracted. The consensus guidelines for PMS were reviewed. Results: This review identified 131 validated assessment tools that were categorized by the intended age group and into specific behavioral domains: Autism spectrum disorder (ASD) screening, adaptive behavior, restricted and repetitive behaviors, challenging/disruptive behaviors, mental health screening, and other miscellaneous behaviors such as avoidance and impulsivity. Discussion: Based on the 2023 consensus guidelines, suggestions were given on which tools would be best for assessing various symptoms and behaviors in PMS. Choosing the best assessment tools to appraise behavior and related symptoms in individuals with PMS will aid clinicians in decision-making and lead to more personalized treatment plans. Full article

Physical education (PE) is commonly justified through its contributions to physical fitness, motor skill development, sport participation, and health-enhancing physical activity. These aims remain important, but they do not fully capture PE’s potential as a curriculum context for lifestyle learning and neurobehavioral well-being. This narrative review used structured literature mapping and conceptual framework development to examine how PE may connect embodied movement experiences with motivation, stress and emotion regulation, self-efficacy, resilience, recovery-related awareness, and lifestyle self-regulation in adolescents and young adults. Literature searches were conducted iteratively in PubMed, Scopus, Web of Science Core Collection, SPORTDiscus, and ERIC, with the final search update completed on 20 June 2026. The synthesis identified a curriculum-to-lifestyle gap: existing evidence more often examines whether PE, physical activity, sport, or physical literacy is associated with health or psychological outcomes than how curriculum, teaching climate, reflection, assessment, and peer interaction may support transferable self-regulatory learning. The review therefore proposes an evidence-informed, curriculum-oriented conceptual framework linking PE design and pedagogy with proximal motivational, emotional, cognitive-regulatory, behavioral, and embodied processes. The framework does not imply that PE automatically improves mental health, directly produces neurobiological change, or replaces specialist care. Evidence is stronger for proximal educational processes than for sustained transfer beyond PE. Future research should test clearly specified curriculum mechanisms, implementation conditions, assessment approaches, and longitudinal transfer. Full article

Pediatric sleep-disordered breathing (SDB) is underdiagnosed despite its associations with adverse neurobehavioral, psychosocial, and cardiometabolic outcomes. Pediatric dental providers routinely evaluate craniofacial growth and maintain longitudinal contact with children, yet practical approaches for integrating SDB risk assessment into dental settings remain limited. This protocol describes a prospective, cross-sectional observational study that will enroll 60 school-aged children aged 8–13 years from a university-based pediatric dental clinic and classify them as low-risk or high-risk for SDB using the Pediatric Sleep Questionnaire (PSQ; threshold ≥ 0.33). The primary aim is to examine associations between PSQ-based risk classification and objective physiologic sleep parameters, including the Apnea–Hypopnea Index, Respiratory Disturbance Index, Sleep Apnea Indicator, and Sleep Quality Index, obtained from a U.S. Food and Drug Administration-cleared wearable home sleep monitor—SleepImage Ring (MyCardio LLC, Denver, CO, USA)—worn for a minimum of three consecutive nights. Secondary aims will evaluate associations between SDB risk classification and body mass index, Mallampati score, Brodsky tonsillar grade, and psychosocial functioning (anxiety, depression, perceived stress, and daytime sleepiness). Exploratory craniofacial analyses will be conducted among participants with clinically available lateral cephalometric radiographs. This protocol could position pediatric dental visits as an accessible touchpoint for early identification of children with unrecognized SDB and inform pathways for timely referral. Protocol Version: 1.4, dated 13 May 2026. Trial Registration: ClinicalTrials.gov NCT07581938. Full article

Background/Objectives: Chronic stress and neuroinflammation (promoted by micro- and astroglia) represent key factors in affective pathogenesis. Complementing rodent models, zebrafish (Danio rerio) are widely used in experimental modeling of affective disorders. Here, we examined the effects of chronic treatment with two distinct anti-inflammatory drugs, minocycline and nimesulide, on behavior and neuroinflammation-related biomarker genes in the zebrafish chronic unpredictable stress (CUS) model. Methods: Following two-week CUS with or without drug treatment, fish were assessed using the novel tank test for anxiety-like behavior, and the zebrafish tail immobilization (ZTI) test for depression-like behavior. Results: A 14-day treatment with minocycline (50 mg/L) reduced general motor activity and brain expression of both pro-inflammatory (nos2a) and anti-inflammatory (arg1) microglial biomarker genes, as well as upregulated the anti-inflammatory astrocytic marker s100a10. In CUS-exposed fish, this treatment attenuated depression-like ZTI immobility behavior and downregulated both pro-inflammatory (nos2a, cox2) and anti-inflammatory (arg1, ptx) glial biomarkers compared to the stress-only control. In contrast, one-week nimesulide treatment during CUS produced an anxiolytic-like effect and normalized the expression of stress-induced pro-inflammatory glial biomarkers cox2 and il1β. Conclusions: Overall, our findings suggest that the two anti-inflammatory drugs tested modulate behavioral and molecular responses to chronic stress in zebrafish, with minocycline demonstrating broader anti-neuroinflammatory and antidepressant-like effects, and nimesulide exhibiting more specific anxiolytic-like properties in this model. Full article

Global plastic production and inadequate waste management have led to widespread environmental contamination with microplastics (MPs), now detected in food, water, and air. Their small size, diverse polymer composition, and capacity to carry chemical additives and co-pollutants facilitate intestinal uptake and raise concerns about their potential impact on gut microbiota. This review synthesizes current evidence on how MPs influence gut microbial composition and function, gut barrier integrity, and associated inflammatory and metabolic pathways. We conducted a narrative review of in vivo animal studies, in vitro simulated gut systems, and human observational studies that assessed MP exposure, gut microbiota profiles, and downstream toxicological outcomes. MPs originate from primary and secondary sources and can act as vectors for metals and organic pollutants. Following ingestion, they may cross the intestinal barrier via endocytic and persorption routes, acquire a protein corona, and be recognized by immune cells, activating TLR/NF-κB, and MAPK pathways alongside oxidative stress. In these models, MP exposure induces dysbiosis, characterized by loss of beneficial SCFA-producing bacteria (e.g., Bifidobacterium, Lactobacillus, Bacteroides) and expansion of pathobionts (e.g., Escherichia/Shigella, Staphylococcus, Enterobacteriaceae), accompanied by altered bile acid metabolism. These microbiota and metabolic alterations are linked to increased gut permeability, intestinal inflammation, metabolic dysfunction, and, in some studies, reproductive and neurobehavioral effects. Current evidence supports MPs as emerging modulators of gut microbial and intestinal homeostasis. However, heterogeneity across experimental models, reliance on high exposure doses, and lack of standardized MP characterization limit robust risk assessment. These limitations underscore the need for harmonized methodologies, longitudinal large-scale human studies, and the development of targeted mitigation strategies. Full article

Hypoxic stress disrupts homeostasis, provoking neuroendocrine and oxidative responses that manifest as behavioral impairments and biochemical alterations, with elevated corticosterone and oxidative damage as hallmark features. Solanum campylacanthum, traditionally used as a pest deterrent, lacks empirical validation, though its synonym S. incanum exhibits antioxidant activity. This study evaluated ethanol extract of S. campylacanthum leaves (EESC) in male Wistar rats subjected to repeated hypoxic stress by daily 20 min exposures in sealed transparent chambers over 14 days, creating a hypoxic–hypercapnic environment that induced neurobehavioral and biochemical alterations. EESC significantly alleviated anxiety, depressive-like behaviors, locomotor deficits, and memory decline, while reducing corticosterone and malondialdehyde, enhancing antioxidant defenses, and preventing adrenal hypertrophy. These findings highlight EESC’s adaptogenic and neuroprotective potential under hypoxic stress. Full article