Search Results (46,205)

Sleep disturbances represent one of the most frequent and clinically significant comorbidities in children with autism spectrum disorder (ASD), affecting approximately 50–80% of individuals. Clinically, these disturbances encompass a broad spectrum of disorders, including insomnia, parasomnias, sleep-related movement disorders, and sleep-related breathing disorders, commonly presenting with prolonged sleep latency, frequent nocturnal awakenings, reduced total sleep time, and alterations in sleep architecture. Circadian rhythm dysregulation, abnormalities in neurotransmitter systems such as GABA and serotonin, and altered melatonin signaling have been consistently implicated. These processes may reflect underlying genetic and metabolic influences affecting circadian clock regulation and synaptic function. The management of sleep disturbances in ASD requires a comprehensive approach combining behavioral strategies, caregiver education, and sleep hygiene interventions, while pharmacological options, particularly melatonin, may be considered when non-pharmacological measures are insufficient. Understanding the multifactorial mechanisms underlying sleep disturbances in ASD is essential for improving early recognition and developing individualized therapeutic strategies. This review synthesizes current evidence on the prevalence, biological mechanisms, clinical manifestations, and management of sleep disturbances in ASD, providing an integrated perspective for both clinicians and researchers. Full article

Objectives: The Arch Index (AI) is commonly used to assess medial longitudinal arch morphology; however, values obtained using different measurement technologies may not be interchangeable. This study aimed to compare AI values derived from optical pedography and a barometric platform during bilateral static stance assessment in children and to evaluate their agreement. Methods: Thirty-eight healthy children aged 5–10 years underwent standardized bilateral static foot assessment. AI was calculated using identical segmentation and formula for both systems. Paired t-tests, Pearson correlation, intraclass correlation coefficient, and Bland–Altman analysis were used to assess agreement between methods. Results: Optical pedography produced significantly higher AI values than barometric assessment for both the left (0.284 ± 0.055 vs. 0.188 ± 0.092) and right foot (0.286 ± 0.048 vs. 0.169 ± 0.072; p < 0.001). Agreement between methods was moderate (ICC = 0.494–0.581), with wide limits of agreement. Inter-method differences increased with age. Conclusions: AI values obtained from optical pedography and barometric platforms are not interchangeable in children. Consistent use of a single measurement technology is recommended in pediatric assessment to avoid misinterpretation of developmental changes. Full article

Background/Objectives: Executive function (EF) impairments are common in neurodevelopmental disorders but are often examined using group-level approaches that may overlook clinically meaningful cognitive heterogeneity. This study explored EF heterogeneity in children with attention deficit hyperactivity disorder (ADHD), developmental dyslexia, and comorbid presentations using a clinically grounded mixed-method approach. Methods: Standardized neuropsychological data from the NEPSY-II, WISC-IV, and Woodcock–Johnson IV batteries were integrated with a case-based thematic synthesis of 11 clinical evaluations. Semi-inductive analysis was informed by preliminary patterns observed in a larger clinical sample. Results: Three executive function profiles were identified: (1) globally reduced executive functioning, characterized by widespread deficits in inhibition, attention, and working memory; (2) verbal–mnestic executive vulnerability, marked by weaknesses in verbal memory and attention regulation despite relative cognitive strengths; and (3) selective executive control deficit, reflecting impairments in inhibitory control and self-regulation. These profiles revealed clinically meaningful patterns that were not fully captured by categorical diagnostic classifications. Conclusions: The findings support the value of integrated, profile-based approaches for understanding executive function heterogeneity in neurodevelopmental conditions. Such approaches may enhance ecological validity in assessment and contribute to individualized intervention planning. Given the exploratory and case-based nature of the study, the findings should be considered preliminary and hypothesis-generating. Full article

Background/Objectives: Phenylketonuria (PKU) is a rare autosomal recessive disorder caused by phenylalanine hydroxylase (PAH) deficiency, impairing the conversion of phenylalanine (Phe) to tyrosine. Although early diagnosis and intervention yield excellent outcomes, dietary adherence often declines in adulthood, potentially leading to poor metabolic control and adverse nutritional consequences. This study aimed to evaluate physical activity levels, nutritional status, metabolic control, and anthropometric outcomes in adults with classic PKU, which have not been sufficiently researched in the current literature. Methods: This cross-sectional study included 100 adults with classical PKU (cPKU; baseline phenylalanine levels ≥ 1200 µmol/L) under regular follow-up at the Division of Metabolism, Hacettepe İhsan Doğramacı Childrens’ Hospital. Sociodemographic traits and dietary behaviors were evaluated through structured interviews carried out by a dietitian. Dietary intake was assessed by using a 24 h dietary recall method, and nutrient analyses were performed with the Bebis 7.2 software program. Using the short version of the International Physical Activity Questionnaire (IPAQ), physical activity levels were specified, and participants were categorized according to established scoring criteria. Results: A hundred adults with classical PKU took part in the study, including 47 males and 53 females, with a mean age of 23.84 ± 5.41 years; 5% of participants were underweight, 40% had normal weight, 39% were overweight, and 16% were listed as obese. The intake of mean daily energy is 2443.8 ± 384.6 kcal for men and 1822.5 ± 312.7 kcal for women. Carbohydrates contributed approximately 61% of total daily energy intake in both genders, whereas protein accounted for 12–13% and fat for approximately 26–27% of total energy intake; 17% of participants were physically inactive, 40% were minimally active, and 43% met criteria for sufficient physical activity according to IPAQ-based classification. Energy intake, the use of Phe-free protein substitutes, and BMI were significantly higher in the sufficiently active group compared to the low-active group in men, while no significant differences were observed between physical activity groups among women. Conclusions: Adults with classical PKU showed a high prevalence of overweight and obesity, together with differences in dietary intake and physical activity patterns. Physical activity levels were associated with several nutritional and metabolic characteristics; however, further long-term research is required to fully understand these connections. Full article

The quantitative identification of heavy metal sources is essential to clarify their relationships with ecological and health risks. This study focused on the Manghe Watershed in Jiyuan City, Henan Province, China, integrating the Positive Matrix Factorization (PMF) model, ecological risk index (RI), and health risk assessment (HRA) to construct a coupled PMF-RI/PMF-HRA framework to quantify source-specific risk contributions and propose targeted mitigation strategies. Key findings included: (1) Among the 121 surface soil samples, Cr and Ni showed natural background levels, while Cd, Pb, Hg, Zn, As, and Cu exceeded regional backgrounds by 1.63–33.65 times with anthropogenic-driven spatial heterogeneity. (2) The PMF identified four sources: natural–agriculture mixed (42.65%), the main contributor to Cr, Ni, As, and Cu; industrial activity (24.99%), the primary source of Cd and Zn; traffic–agriculture mixed (20.99%), primarily emitting Pb and As; and coal combustion (11.36%), dominating Hg emissions. (3) Ecological and health risks were governed by heavy metal toxicity and exposure pathways rather than mere concentration levels. Specifically, industrial sources (Cd, Zn) should be prioritized for ecological risk control, whereas natural–agricultural mixed sources (As, Pb, Cr) should be prioritized for health risk control. Oral ingestion was the dominant exposure pathway for both non-carcinogenic risk and carcinogenic risk in children, with the natural–agricultural mixed source contributing the most to this pathway. (4) The total carcinogenic risk (TCR) for children was 1.17 × 10⁻⁴, which exceeds the commonly accepted unacceptable threshold of 1 × 10⁻⁴, indicating a potential carcinogenic concern. (5) The PMF-RI and PMF-HRA frameworks quantitatively proved that the main sources of ecological risks and health risks may be completely different, and this phenomenon was jointly regulated by the toxicity response coefficient and exposure pathways. A “source–risk-pathway” quantitative attribution was achieved and provides clear support for targeted interventions, emphasizing source control for industrial emissions (Cd-Zn), traffic–agriculture inputs (Pb-As), and coal-derived Hg, alongside optimized agricultural practices. Full article

Whilst all asylum seekers find themselves in a difficult position while trying to be recognised as refugees, some are in more perilous situations than others. Those asylum seekers that are unaccompanied (UAS) children are manifestly in greater need of care and protection than most adult asylum seekers, given their minority (under 18) and being without the protection of a primary carer. Any child who is in the care of the state should always be placed in age-appropriate and safe accommodation and in the care of staff who are properly trained; UAS children are no different. Typically, these functions are performed by local authorities through their social work departments. However, the UK’s previous Conservative government’s practice of using hotels to accommodate UAS children in England from 2021–2024 fell short of its human rights obligations towards UAS children. This paper argues that through this and related policies, the government was actively involved in compounding the victimisation of already susceptible children who had fled their country of origin thinking (mistakenly) that their human rights would be respected here. Full article

Interpreting HNF1B variants is challenging in clinical practice. We aimed to integrate functional, clinical, and family data to improve variant classification, describe clinical features of carriers and report registry-level prevalence of HNF1B alterations. Clinical, genetic, and family data were analyzed from the Norwegian MODY Registry (NMR) and the Norwegian Childhood Diabetes Registry (NCDR). Clinical features of sequence variant and 17q12 deletion (17q12del) carriers were summarized, and variants were classified using ACMG-AMP-ClinGen criteria. Registry-level prevalence was reported with 95% confidence intervals. HNF1B sequence variants were functionally assessed, showing that lower transactivation (TA) was associated with higher clinical severity. Eleven variants demonstrated impaired functional activity, with TA inversely correlated with clinical burden (ρ = −0.701, p = 0.002). We identified 28 individuals with 17q12del (21 in NMR, seven in NCDR) and 15 individuals carrying 14 unique pathogenic/likely pathogenic (P/LP) sequence variants, all detected in the NMR. Overall, 36/486 probands (7.4%) with genetically confirmed monogenic diabetes in the NMR carried a P/LP HNF1B sequence variant or 17q12del. In the NCDR, ~0.2% carried 17q12del (7/3583; 3/7 GADA/IA-2A-positive). Functional data enabled reclassification of three variants. Since many pediatric 17q12del carriers in the NMR were referred for testing due to structural renal anomalies without diabetes, HNF1B screening should be considered in children with renal/extra-renal features, irrespective of diabetes or autoantibody status. Full article

Enterovirus B (EVB) is the most prevalent species of human enteroviruses, responsible for a wide range of diseases, including hand, foot, and mouth disease, viral meningitis, myocarditis, and neonatal sepsis, imposing a significant disease burden primarily on children. Coxsackievirus B (CVB1-6) and various echovirus (E) serotypes are the major serotypes of EVB. Since no antiviral drug or vaccine is available, it is important to strengthen monitoring, risk assessment, and early warning of genomic variations for EVB. CVB1, CVB3, E6, and E30 were selected as representative EVB serotypes for this study due to the availability of three-dimensional structures and their global prevalence. To evaluate the mutation effects of structural proteins on structural stability and receptor-binding affinity, computational saturation mutagenesis of EVB serotypes was performed using FoldX. Furthermore, based on data from deep mutational scanning for CVB3, a risk prediction model for EVB fitness was constructed by machine learning algorithms and applied to other EVB serotypes. Finally, we integrated three phenotypes—structural stability, receptor-binding affinity and fitness—to evaluate genomic variation risk of EVB and tracked the prevalence of high-risk mutants in natural viral sequences through molecular evolution analysis and mutation profiles. We identified the N-terminus and C-terminus of VP1 and the EF loop of VP2 as the EVB regions of highest genomic variation risk, and high-risk mutations had played significant roles in viral evolutionary history. These findings provide a framework for multi-phenotypic and multi-data approaches to viral risk assessment and offer insights to support the development of antiviral drugs and vaccines. Full article

Background: Staphylococcus aureus neonatal osteomyelitis (SA-NOm) is a rare condition with the potential for lifelong skeletal morbidity. Available evidence remains scarce and inconsistent, with notable differences in clinical presentation, therapeutic regimens, and reported outcomes, underscoring the need for a systematic evaluation combining clinical experience with existing literature. Methods: We retrospectively reviewed data from all neonates admitted to Regina Margherita Children’s Hospital, Turin, Italy, between 2017 and 2024 with a diagnosis of SA-NOm. A structured narrative review of the pertinent literature published over the past 25 years was conducted to identify additional cases and compare management approaches. Results: Four neonates with SA-NOm were identified at our center (institutional cohort) while a literature review retrieved 38 additional cases (literature cohort) to establish a combined cohort (n = 42). Of these, 78% were born at term, with a male-to-female ratio of 1.6:1 (26 males, 16 females). Approximately half of the combined cohort presented identifiable risk factors for SA-NOm, including neonatal intensive care unit admission, prematurity, sepsis, or maternal complications. Across the combined cohort, the mean age at presentation was 19 days. The most common presenting signs were local swelling and reduced mobility of the affected limb, although systemic symptoms often complicated early recognition. Long bones were most frequently involved—particularly the femur, humerus, and tibia—with equal distribution between upper and lower extremities. The mean intravenous antibiotic duration for the combined cohort was 31.6 days, followed by two to three weeks of oral therapy. Empiric regimens varied, including glycopeptides alone or combined with second- or third-generation cephalosporins, anti-staphylococcal penicillins, or carbapenems. Sequelae rates were rarely reported in the literature, likely due to limited follow-up, whereas extended surveillance in our cohort revealed substantial long-term morbidity, including restricted joint mobility, limb length discrepancy, and persistent radiographic abnormalities. Conclusions: SA-NOm, due to its rarity and potential for long-term skeletal sequelae, requires early diagnosis and timely empiric antibiotic therapy based on local resistance data. Prospective multicenter studies are needed to define standardized diagnostic and therapeutic protocols. Full article

Autism spectrum disorder (ASD) is classified as a neurodevelopmental disorder with an increasingly high incidence rate. Increasing awareness, changing diagnostic criteria and social attitudes, as well as financial considerations, will affect the prevalence of diagnosis. The symptoms of ASD vary widely, making it difficult to detect. It represents a spectrum of alterations ranging from mild indications to severe impairments and diagnosis is based on a very rigorous behavioral assessment. Nevertheless, certain neuropathological changes are common, although the background of this disorder remains still unknown. Therefore, some research aimed at better understanding the pathology of the neurological alterations in ASD, as well as the possibilities for early diagnosis and treatment of this disorder, is urgently needed. This review summarizes the current evidence on some selected proteins such as tau protein, NFL, and BDNF as well as IGF-1 that appear to be the best protein candidates for better understanding the causes of autism, as well as for use as fluid biomarkers in the diagnosis and monitoring of ASD. Full article

Human milk is widely recognised as the optimal source of nutrition for newborns and infants, providing not only an ideal macronutrient composition but also a range of bioactive components that exert important non-nutritional functions, and as such it represents the first functional food consumed in early life. Among these bioactive components, the human milk oligosaccharides (HMOs)—a structurally diverse family of glycans present in human milk at concentrations 100- to 1000-fold higher than in the milk of other mammalian species—have emerged as multifunctional contributors to the establishment of the intestinal microbiome, immune development, anti-infective defence, and epithelial barrier integrity during a developmental window characterised by immune immaturity. The aim of the present narrative review is to synthesise current evidence on the anti-infective properties of HMOs in infancy and to integrate, within a single framework, five interconnected mechanisms through which HMOs protect the infant against infection: glycan-mimicry-based competitive inhibition of pathogen adhesion, direct antimicrobial and antibiofilm activity, selective prebiotic shaping of the gut microbiome, modulation of innate and adaptive immune responses, and reinforcement of mucosal barrier integrity in the gut and lungs. Breastfeeding constitutes a natural strategy for anti-infective protection in early childhood, while infant formulas supplemented with biotechnologically produced HMOs that are structurally identical to those in human milk provide measurable benefits for non-breastfed infants. Full article

Pharmaceutical and microbial pollution in urban rivers is an emerging concern, particularly in developing regions with limited wastewater treatment capacity, posing risks to human health and ecosystems. This study evaluated the risk profiles of selected pharmaceutical compounds and bacterial indicators in the Sand River, South Africa, and computed their ecological risks, antimicrobial resistance (AMR), and human health risk assessment. Surface water samples were collected from three sites during the wet season and analyzed for target antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) using High-Performance Liquid Chromatography (HPLC) with a photodiode array (PDA) detector, while total coliforms (TCs) and Escherichia coli (E. coli) were enumerated using the Colilert system. Ciprofloxacin, sulfamethoxazole, and erythromycin were the most abundant pharmaceuticals, with maximum concentrations of 2.50 µg/L, 2.76 µg/L, and 2.53 µg/L, respectively. TC and E. coli levels exceeded regulatory thresholds, indicating severe microbial contamination. Risk quotient analysis identified ciprofloxacin, erythromycin, and trimethoprim as high-risk compounds for potential resistance selection (RQ ≥ 1), while ciprofloxacin and erythromycin posed significant ecological risks to fish. Although non-carcinogenic health risk assessment remained below concern (HI < 1), children showed higher exposure levels. These findings underscore the urgent need for improved pharmaceutical waste management and wastewater treatment infrastructure. Full article

Background and Aim: The gluten-free diet (GFD) can have a huge impact on the quality of life of people with celiac disease (CD), especially on a social level. The objective of this work is to evaluate a structured nutrition education program focused on CD and GFD that aims to increase knowledge and improve inclusion attitudes about the disease in children. Methods: This is a one-month intervention for school children aged 10–12 years called Zeliakide (8 sessions). It was carried out through a STEAM methodology, using inquiry-based learning. The participants responses were evaluated through questionnaires before and after the intervention, and participants were also followed up one month later. The control group was a similar group of students who followed their regular school curriculum. Results: 299 children from one school of Vitoria-Gasteiz took part in the study (155 intervention group; 144 control group). Zeliakide significantly improved knowledge about CD and GFD in children, and this knowledge was retained for one month. Concretely, students increased their ability to explain what CD is, to assess gluten, and to classify food groups according to gluten content. The intervention contributed to augmenting the selection of behaviors to overcome differences between individuals, assessed one month after the intervention. In addition, the program allowed students to understand the work of scientists. Conclusions: Zeliakide can contribute to nutrition education initiatives that aim to improve knowledge of CD and GFD in the general population, while promoting empathetic behavior towards people with CD. Registration: clinicaltrials.gov, NCT05467865 on 21 July 2022. Full article

Background: Microvascular free flap reconstruction is an established method for the management of complex head and neck defects in pediatric patients. However, the influence of perioperative anesthetic management on flap outcome in this population remains insufficiently defined. The aim of this study was to evaluate the association between selected perioperative anesthetic factors and flap outcome in pediatric patients. Methods: This retrospective observational study included pediatric patients undergoing microvascular free flap reconstruction between August 2011 and July 2020. Of 80 screened patients, 56 met the inclusion criteria based on complete medical records. Demographic, surgical, and perioperative anesthetic variables were collected. Continuous variables were compared using the Mann–Whitney U test, and categorical variables using the chi-squared test with Yates’ correction. Correction for multiple testing was performed using the Benjamini–Hochberg false discovery rate procedure. Results: Complete flap survival was achieved in 50 patients (89.3%), while partial and total flap loss occurred in 3 patients each (5.4%). No significant associations with flap loss were identified for the type of anesthetic gas, opioid use, induction agents, intraoperative fluid therapy, diuresis, rocuronium dose, or operation time. Lower weight-adjusted doses of midazolam and propofol showed borderline unadjusted associations with flap loss; however, these differences did not reach statistical significance after correction for multiple testing. Patients with flap loss had a higher mean intraoperative body temperature compared to those with successful flap survival (36.65 °C vs. 36.05 °C; p < 0.05). Conclusions: In pediatric head and neck free flap reconstruction, most analyzed perioperative anesthetic factors were not associated with flap outcome. Dose-related findings for midazolam and propofol should be interpreted as exploratory and non-significant after correction for multiple testing, while higher intraoperative body temperature was associated with flap loss. However, these results are exploratory, cannot establish causality, and require confirmation in larger, preferably multicenter studies with adjustment for surgical and patient-related confounders. Full article

Importance: A comprehensive analysis of childhood cancer and cancer predisposition syndromes (CPSs) incidence can provide insights that lead to improvements and modifications in treatment protocols through personalized therapy, thereby reducing toxicity. Purpose: This study aimed to analyze age-specific hospital-based childhood cancer rates and the distribution of CPSs in a 20-year pediatric cohort from the region. Materials: A total of 2190 patients, aged from birth to 17 years, diagnosed with any type of neoplasm classified by ICD-10 codes at Karol Jonscher’s Clinical Hospital of Poznan University of Medical Sciences (KJCH PUMS) between 1 January 2000, and 31 December 2019, were included, with 193 (8.8%) having an underlying CPS. Results: The pediatric population of the Greater Poland Region has declined over the past two decades. The most common diagnoses can be grouped into three main categories: (1) leukemias, involving 704 patients (32.1%); (2) central nervous system (CNS) tumors, represented by 382 children (17.4%); and (3) lymphomas, including 279 patients (12.7%), together accounting for 1353 cases (61.8%). The age-specific hospital-based case rate for childhood cancer (all types combined) peaked in the 0–28 days age group at 71.8 per 100,000 person-years (95% CI: 52.2–96.4), with a trend to decrease with age and a slight increase among adolescents aged 16–17 years (13.6 per 100,000, 95% CI: 12.0–15.4). The age-specific incidence of CPS-positive cancers declined from 18.0 (95% CI: 8.2–29.4) per 100,000 person-years in the first month of life to 0.7 (95% CI: 0.3–1.2) in 16–17-year-olds. CPS-positive children were diagnosed at significantly younger ages for four cancer types: liver and intrahepatic bile duct tumors (C22: A = 0.097, adjusted p < 0.001), myeloid leukemia (C92: A = 0.179, adjusted p < 0.001), lymphoid leukemia (C91: A = 0.309, adjusted p = 0.007), and renal tumors (C64: A = 0.335, adjusted p = 0.013). Conclusions: CPSs likely play a significant and underestimated role in pediatric cancers, especially during early childhood. Improving access to genetic testing could greatly enhance risk assessment, personalized treatment, and long-term outcomes in pediatric oncology. Full article