Search Results (5,942)

Objective: Irritability and reactive aggression are transdiagnostic features that are predictive of adverse long-term outcomes. This investigation examined whether intranasal oxytocin administration impacts the interaction between irritability and reactive aggression, and whether these effects can be detected at a neural level via a facial expression processing task during functional MRI (fMRI). Methods: In this study, 40 children and adolescents with severe irritability and psychiatric diagnoses of disruptive mood and behavioral disorders were assigned to either intranasal oxytocin or placebo administration over a 3-week period in a randomized, double-blind trial (ClinicalTrials, NCT02824627). Clinical measures and fMRI during a facial expression processing task were collected pre- and post-intervention. Brain regions sensitive to oxytocin administration were determined using whole-brain statistical analyses, with post hoc analyses to determine whether changes in the neural activity mediated the relationship between changes in irritability and reactive aggression across the intervention period. Results: Youth who received intranasal oxytocin administration exhibited significant decreases in irritability and reactive aggression compared to their counterparts in the placebo group. Further, oxytocin administration was associated with significant increases in neural activity in the right superior prefrontal cortex, which fully mediated the relationship between improvements in irritability and improvements in reactive aggression. Conclusions: Intranasal oxytocin significantly reduced irritability and reactive aggression in youth, as well as neural activity in the prefrontal cortex, such that increases in the cortical activity fully mediated the relationship between changes in irritability and reactive aggression. Taken together, these findings may reflect oxytocin-related enhancements in emotional regulation in youth with severe irritability, a potential therapeutic mechanism for mitigating reactive aggression. Full article

Background/Objectives: Adolescence is a critical period for the early detection of metabolic syndrome (MetS), a condition that increases the risk of cardiometabolic diseases in adulthood. Timely identification of at-risk adolescents enables targeted prevention strategies. This study aimed to analyze the discriminative capacity and accuracy of six biochemical and/or anthropometric indices related to lipid metabolism and adiposity for the early detection of MetS in a sample of Spanish adolescents. Methods: A cross-sectional study carried out according to the STROBE guidelines. A sample of 981 adolescents aged 11–16 years old were randomly recruited from schools in Southeastern Spain. The presence or absence of MetS was determined according to the International Diabetes Federation criteria. The following biochemical and/or anthropometric indices were evaluated: triglyceride glucose index, visceral adiposity index, logarithm children’s lipid accumulation product, triglyceride glucose-body mass index, triglyceride glucose-waist circumference, and triglyceride glucose-waist-to-hip ratio. Results: The triglyceride glucose-waist-to-hip ratio and triglyceride glucose-body mass index parameters were the strongest indicators associated with MetS in boys and girls, respectively, after adjusting for several factors. Moreover, all evaluated indices showed optimal AUC values, with the visceral adiposity index and triglyceride glucose-waist circumference index exhibiting the highest discriminative capacity in both genders. Conclusions: The evaluated biochemical and anthropometric indices—particularly visceral adiposity index and triglyceride-glucose-waist circumference—show promise as accessible biomarkers for identifying adolescents at metabolic risk. These indices may serve as practical tools in preventive health strategies aimed at improving metabolic health by screening adolescents at risk of MetS, thereby helping to reduce the future burden of non-communicable diseases. Full article

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article

Background/Objectives: Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents; the survival rate is as low as 24%. Accurate prediction of clinical outcomes remains a challenge due to tumor heterogeneity and the complexity of pediatric cases. This study aims to improve predictions of progressive disease, therapy response, relapse, and survival in pediatric OS using MRI-based radiomics and machine learning methods. Methods: Pre-treatment contrast-enhanced coronal T1-weighted MR scans were collected from 63 pediatric OS patients, with an additional nine external cases used for validation. Three strategies were considered for target region segmentation (whole-tumor, tumor sampling, and bone/soft tissue) and used for MRI-based radiomics. These were then combined with clinical features to predict OS clinical outcomes. Results: The mean age of OS patients was 11.8 ± 3.5 years. Most tumors were located in the femur (65%). Osteoblastic subtype was the most common histological classification (79%). The majority of OS patients (79%) did not have evidence of metastasis at diagnosis. Progressive disease occurred in 27% of patients, 59% of patients showed adequate therapy response, 25% experienced relapse after therapy, and 30% died from OS. Classification models based on bone/soft tissue segmentation generally performed the best, with certain clinical features improving performance, especially for therapy response and mortality. The top performing classifier in each outcome achieved 0.94–1.0 validation ROC AUC and 0.63–1.0 testing ROC AUC, while those without radiomic features (RFs) generally performed suboptimally. Conclusions: This study demonstrates the strong predictive capabilities of MRI-based radiomics and multi-region segmentations for predicting clinical outcomes in pediatric OS. Full article

Background: Bullying is a significant problem worldwide and in Lithuania, especially among children and adolescents. This study aimed to assess the associations of bullying with adolescents’ subjective sense of happiness and general health. Methods: A cross-sectional study was conducted using an anonymous written questionnaire. Adolescents at various schools across Lithuanian cities and districts were surveyed to investigate the frequency of bullying among them over the past six months and its impact on their subjective sense of happiness and well-being. Results: This study included 4124 students from seventh to tenth grade; their average age was 14.48 ± 1.15 years, with 49.35% being boys. Over the past six months, the highest bullying incidence occurred at school, accounting for 25.79% of the cases. Only half of the respondents (48.81%) felt happy, and a little more than half felt healthy (63.11%). It was found that bullying at school (ρ_s = −0.224; ρ_s = −0.197), outside school (ρ_s = −0.207; ρ_s = −0.180), and online (ρ_s = −0.175; ρ_s = −0.110) is associated with adolescents’ sense of happiness and health. Conclusion: Bullying is common among Lithuanian adolescents and has a negative impact on their subjective happiness and well-being. It is crucial to develop prevention initiatives to decrease bullying in schools and within the community. Full article

The purpose of this study was to examine vegetable consumption and its relationship with lifestyle characteristics among children and adolescents. Data from a health survey administered to a representative sample of 177,091 schoolchildren between the ages of 8 and 17 were employed in this observational, cross-sectional investigation. Physical activity level, screen time, and sleeping patterns were assessed using self-completed questionnaires. Vegetable consumption and dietary habits were analyzed using the Mediterranean Diet Quality Index for Children and Adolescents. Participants consuming vegetables more than once daily were categorized as consumers vs. non-consumers. Physical education teachers measured anthropometric and physical fitness factors. Descriptive statistics and binary logistic regression analysis were conducted, and the odds ratio with the corresponding 95% confidence interval was calculated and adjusted for confounders. Vegetables were consumed once or more times a day by more females than males (25.5% vs. 24.0%, p < 0.001). In both sexes, vegetable consumers slept more, ate healthier, spent less time on screens, and had better anthropometric and aerobic fitness measurements than non-consumers. Healthy eating practices, such as regularly consuming fruits, legumes, nuts, and dairy products, were strongly correlated with vegetable intake. For every one-year increase in age, the odds of being a vegetable consumer decreased by 8% and 10% in boys and girls, respectively. Overweight/obese participants had lower odds of being a vegetable consumer by 20%. Increased screen time, inadequate physical activity, and insufficient sleeping hours decreased the odds of being a vegetable consumer by 22%, 30%, and 25%, respectively (all p-values < 0.001). Overall, a healthier lifestyle profile was associated with higher vegetable intake for both sexes among children and adolescents. Full article

Background/Objectives: Autism spectrum disorder (ASD) has been extensively studied through neuroimaging, primarily focusing on grey matter and more in children than in adults. Studies in children and adolescents fail to capture changes that may dampen with age, thus leaving only changes specific to ASD. While grey matter has been the primary focus, white matter (WM) may be more specific in identifying the particular biological signature of the neurodiversity of ASD. Diffusion tensor imaging (DTI) is the more appropriate tool to investigate WM in ASD. Despite being introduced in 1994, its application to ASD research began in 2001. Studies employing DTI identify altered fractional anisotropy (FA), mean diffusivity, and radial diffusivity (RD) in individuals with ASD compared to typically developing (TD) individuals. Methods: We systematically reviewed literature on 21 May 2025 on PubMed using the following strategy: (“autism spectrum”[ti] OR autistic[ti] OR ASD[ti] OR “high-functioning autism” OR Asperger*[ti] OR Rett*[ti]) AND (DTI[ti] OR “diffusion tensor”[ti] OR multimodal[ti] OR “white matter”[ti] OR tractograph*[ti]). Our search yielded 239 results, of which 26 were adult human studies and eligible. Results: Analysing the evidence, we obtained regionally diverse WM alterations in adult ASD, specifically in FA, MD, RD, axial diffusivity and kurtosis, neurite density, and orientation dispersion index, compared to TD individuals, mostly in frontal and interhemispheric tracts, association fibres, and subcortical projection pathways. These alterations were less prominent than those of children and adolescents, indicating that individuals with ASD may improve during brain maturation. Conclusions: Our findings suggest that white matter alterations in adults with ASD are regionally diverse but generally less pronounced than in younger populations. This may indicate a potential improvement or adaptation of brain structure during maturation. Further research is needed to clarify the neurobiological mechanisms underlying these changes and their implications for clinical outcomes. Full article

Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate the effect of a stress management protocol with diaphragmatic breathing (DB) and physiotherapy exercise on stress, body composition, cardiorespiratory and metabolic markers of children and adolescents with morbid obesity. Methods: The study included 31 children and adolescents (5–18 years old) with morbid obesity (22 in the intervention arm and 9 controls). All participants completed anxiety questionnaires and a self-perception scale. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), blood pressure (BP) and SpO₂ were measured. Fasting glucose, uric acid, triglycerides, HbA1c, (AST/SGOT), (ALT/SGPT), HDL, LDL, insulin, ACTH, cortisol, HOMA-IR, 17-OH, S-DHEA, SHBG were assessed, and anthropometric measurements were also performed. Results: In the intervention group, 4 months after the treatment, an improvement was noted in the BMI, BMI z-score, waist-to-height ratio, FEV1, SpO₂, pulse and systolic BP. HDL increased, ALT/SGPT and insulin resistance improved. Positive changes were observed in temporary and permanent stress and self-esteem of children in the intervention group, including anxiety, self-perception, physical appearance, etc. Conclusions: A combined exercise and DB protocol has a positive effect on stress, by improving body composition, reducing insulin resistance, and ameliorating physical and mental health and quality of life of pediatric patients with morbid obesity. Full article

Background: The 2022 conflict in Ukraine triggered mass migration, leading to a significant influx of Ukrainian refugee children into Poland. This situation raises concerns about hepatitis B virus immunity, as Ukraine’s hepatitis B vaccination coverage has been inconsistent compared to Poland’s high vaccination rates. Objective: To evaluate hepatitis B immunity and infection prevalence among Ukrainian refugee children residing in Southern Poland and to assess implications for vaccination strategies in the host country. Methods: A prospective cross-sectional study was conducted on 1322 Ukrainian refugee children (0–18 years) presenting to a pediatric infectious diseases department in Southern Poland between February 2022 and March 2024. Data on vaccination history, demographic characteristics, and selected laboratory parameters, including hepatitis B surface antigen and anti-HBs antibody levels, were collected. Protective immunity was defined as anti-HBs antibody levels ≥10 IU/L. Results: Among the participants (mean age 9.9 years; 50.2% female), 83.2% were reported as vaccinated according to national immunization programs, but only 64.9% demonstrated protective anti-HBs antibody levels. Protective antibody prevalence declined significantly with age, with less than half of adolescents aged 15–18 years showing immunity. Five children (0.4%) were diagnosed with chronic hepatitis B, four of whom were unvaccinated. Conclusions: This study identifies a significant gap in hepatitis B immunity among Ukrainian adolescent refugees residing in Southern Poland, with less than half possessing protective anti-HBs antibody levels. This immunity gap and the high risk of sexual transmission of the hepatitis B virus in adolescents highlight the urgent need for comprehensive surveillance, screening, and catch-up vaccination programs. Full article

Parental school involvement (PSI) is an important contributor to children’s academic and overall positive development. Such activities as discussing schoolwork and tracking progress can boost children’s motivation and achievements. Although the multifaceted nature of PSI is widely recognized, there are limited reliable measures that comprehensively capture all its dimensions, particularly for children and adolescents. This study aims to develop a measure for assessing children and adolescents’ perceptions of parental involvement based on parent- and teacher-validated self-report measures—the Parental School Involvement Questionnaire—Children’s version (PSIQ-CV). A total of 537 children and adolescents (M_Age = 9.64, SD_Age = 2.43), mainly female (52.8%), from the south of Portugal participated in this study. An exploratory factor analysis (EFA, n = 150) and a confirmatory factor analysis (CFA, n = 387) were carried out. The EFA indicated a three-factor solution (i.e., support in learning activities, parent–school communication, and supervision), supported by the CFA, with good quality-of-fit indices (χ² = 225; df = 101; χ²/df = 2.23; CFI = 0.91; TLI = 0.89; RMSEA = 0.060 [CI: 0.049–0.070]). Our data confirmed that the PSIQ-CV has robust psychometric properties, with acceptable reliability and validity. The PSIQ-CV can be considered a relevant and valid tool for measuring the perception of parental school involvement among children and adolescents, in line with Epstein’s theoretical model, and useful for both researchers and practitioners. Full article

Background: Youth with chronic rheumatologic diseases undergo medical experiences that can lead to post-traumatic stress disorder (PTSD). Understudied in pediatric rheumatology, medical PTSD can be significantly distressing and impairing. Objective: This study explored the prevalence of medical PTSD symptoms in youth with chronic inflammatory arthritis and associated factors, including pain, disease activity, mental health history, and anxiety sensitivity. Methods: A cross-sectional study of 50 youth (ages 8–18) with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematous (cSLE) was conducted at a pediatric rheumatology clinic. Participants completed self-report measures assessing post-traumatic stress symptoms (CPSS-V), pain, anxiety sensitivity (CASI), pain-related self-efficacy (CSES), adverse childhood experiences (ACEs), and fibromyalgia symptoms (PSAT). Clinical data included diagnoses, disease activity, treatment history, and demographics. Results: Forty percent had trauma symptoms in the moderate or more severe range. The 14% likely meeting criteria for probable medical PTSD were older (median 17 vs. 15 years, p = 0.005), had higher pain scores (median 4 vs. 3, p = 0.008), more ACEs (median 3 vs. 1, p = 0.005), higher anxiety sensitivity scores (median 39 vs. 29, p = 0.008), and higher JIA disease activity scores (median cJADAS-10 11.5 vs. 7.5, p = 0.032). They were also more likely to report a history of depression (71 vs. 23%, p = 0.020). No associations were found with hospitalization or injected/IV medication use. Conclusions: Medical trauma symptoms are prevalent in youth with chronic inflammatory arthritis. Probable PTSD was associated with pain and psychological distress. These findings support the need for trauma-informed care in pediatric rheumatology. Full article

Introduction: Sex-specific differences in psychopharmacological treatment have gained increasing attention in adults, with studies showing that women often have higher serum concentrations of psychotropic drugs due to biological differences. However, despite recognition of these differences in adults, reference ranges for therapeutic drug monitoring (TDM) in general, but even more sex-specific therapeutic windows for psychotropic drugs, are lacking in children and adolescents, who may metabolize and respond to medications differently. Aim: The study aimed to investigate sex-specific differences in antidepressant (AD) and antipsychotic (AP) -treatment outcomes, and pharmacokinetics in childhood/adolescence. In particular, we examined differences in AD and AP serum levels and clinical effects, including adverse drug effects (ADEs) and therapeutic effectiveness. Methods: This study is part of the multicenter “TDM-VIGIL” pharmacovigilance project, which prospectively followed patients aged 6–18 years treated with AD and AP across 18 child psychiatric centers in German-speaking countries from 2014 to 2018. Clinical data, including drug concentrations (AD: fluoxetine, mirtazapine, (es)citalopram, sertraline; AP: aripiprazole, quetiapine, olanzapine, risperidone), were collected using an internet-based registry, and treatment outcomes and ADEs were assessed during routine visits. Statistical analyses were performed to examine sex differences in pharmacokinetics and clinical responses, adjusting for age, weight, and other confounders. Results: A total of 705 patients (66.5% girls, 24.7% <14 years, mean age of 14.6 years) were included. Female patients were slightly older, had lower body weight, and were more often diagnosed with depression and anorexia nervosa, while boys were more frequently diagnosed with hyperkinetic disorders and atypical autism. We found no sex differences in the serum concentrations of investigated drugs when adjusted for age and weight. In fluoxetine treatment in patients diagnosed with mood (affective) disorders, female sex was associated with the probability for very good therapy response (p = 0.04), as well as with moderate treatment response (p = 0.02) compared to no treatment response. Discussion: Our findings suggest that sex may not affect serum levels of investigated AD and AP in children/adolescents. However, treatment outcome of fluoxetine was associated with sex, with higher probability for a better outcome in female patients diagnosed with mood (affective) disorders. Full article

Background/Objectives: The aim was to identify patterns of autonomic and neuroendocrine reactivity to an immersive virtual reality (VR) social-emotional stressor and explore their associations with perceived stress and eating behavior. Methods: This one-group pretest–posttest study included 30 children and adolescents with obesity (15 boys and 15 girls), aged 8 to 17 years. The VR protocol consisted of two consecutive phases: a 5 min relaxation phase using the Forest application and a 5 min stimulation phase using a cognitively engaging VR game designed to elicit social-emotional stress. Physiological responses were measured using heart rate variability (HRV) indices and salivary stress biomarkers, including cortisol and alpha amylase. Subjective stress and eating responses were assessed via visual analogue scales (VAS) administered immediately post-exposure. The Three-Factor Eating Questionnaire (TFEQ-R21C) was used to evaluate cognitive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). Results: The cortisol reactivity was blunted and may reflect both the attenuated HPA axis responsiveness characteristic of pediatric obesity and the moderate psychological challenge of the VR stressor used in this study. Two distinct autonomic response patterns were identified via exploratory factor analysis: (1) parasympathetic reactivity, associated with increased RMSSD and SDNN and decreased LF/HF, and (2) sympathetic activation, associated with increased heart rate and alpha-amylase levels and reduced RR intervals. Parasympathetic reactivity was correlated with lower perceived stress and anxiety, but also paradoxically with higher uncontrolled eating (UE). In contrast, sympathetic activation was associated with greater cognitive restraint (CR) and higher anxiety ratings. Conclusions: This study demonstrates that immersive VR game exposure elicits measurable autonomic and subjective stress responses in children and adolescents with obesity, and that individual differences in physiological reactivity are relevantly associated with eating behavior traits. The findings suggest that parasympathetic and sympathetic profiles may represent distinct behavioral patterns with implications for targeted intervention. Full article

Background/Objectives: Internalizing disorders are highly prevalent during adolescence. Previous research has shown that psychological inflexibility (PI) in both adolescents and their parents contributes to internalizing problems. However, how parental and adolescent PI relate to one another in explaining these difficulties remains unclear. The present exploratory study examined whether adolescent PI mediates the relationship between maternal PI and internalizing problems in adolescents. Methods: The study sample included 81 mother–adolescent dyads (80% female adolescents). Mothers completed a general self-report measure of PI, while adolescents completed self-report measures assessing both PI and internalizing problems. Results: The results showed that adolescent PI partially mediated the relationship between maternal PI and internalizing difficulties in female adolescents, whereas the mediation model was not significant for male adolescents. Conclusions: Findings suggest that mothers with high levels of psychological inflexibility may foster similar patterns in their children, particularly in daughters, thereby increasing adolescents’ vulnerability to increased psychological distress. Full article

Background/Objectives: Biofeedback interventions are increasingly utilized in pediatric and adult care, with evidence in treating specific medical conditions and specific symptoms. However, evidence supporting their efficacy among children and adolescents and young adults (AYAs, aged 15–39) with cancer is limited. The aims of this systematic review are to present, assess, and synthesize the existing research on biofeedback in pediatric and AYA oncology, identify gaps in biofeedback research within this population, and provide recommendations for future research and clinical implications. Methods: A systematic search for articles was conducted using six bibliographic databases—PubMed/MEDLINE (NLM), EMBASE (Elsevier), CINAHL (EBSCO), SPORTDiscus (EBSCO), PsycINFO (OVID), and PEDro (NeuRA)—with an update on 5/7/2025. Included were studies involving pediatric/AYA oncology participants (0–39 years old) and those receiving at least one biofeedback modality. The methodological quality and risk of bias among included articles were assessed using the Cochrane Risk of Bias (ROB) Tool (modified version for non-randomized studies). A narrative synthesis of included studies examined the type of cancer studied, type of biofeedback used, study designs and methodological quality, and key outcomes evaluated. Results: While the literature suggests that biofeedback may offer beneficial outcomes for managing various pediatric/AYA oncology-related symptoms, such as pain, anxiety, and fatigue, only 8 studies out of 1013 screened (<1%) met inclusion criteria. Limitations included low study quality (small sample sizes, lack of control groups, and methodological inconsistencies). Conclusions: While biofeedback shows promise as a feasible and effective intervention, there is a call to action for well-designed, methodologically rigorous studies to substantiate its effectiveness and inform evidence-based practice specifically for pediatric/AYA oncology patients and clinicians. Full article