Search Results (4,390)

In the context of research aimed at identifying the causes of the progressive decline in cellular and tissue functions characteristic of aging, in recent decades, increasing attention has been devoted to the sirtuin family. Sirtuins are named after the Sir2 protein of Saccharomyces cerevisiae, a product of the SIR gene family, known as “silent information regulator 2”. Sirtuins are NAD⁺-dependent protein deacetylases and deacylases characterized by a conserved catalytic domain of approximately 275 amino acids. The removal of acetyl groups from acetyl-lysine residues on proteins is critical in regulating a wide range of biological functions, including gene silencing, genome stability, longevity, metabolism, and cellular physiology. In humans, the sirtuin family comprises seven isoforms (SIRT1–SIRT7), each with specific substrate preferences and primarily, but not exclusively, localized in the nucleus (SIRT1, SIRT6, and SIRT7), cytoplasm (SIRT2), and mitochondria (SIRT3, SIRT4, and SIRT5). Sirtuins may regulate numerous cellular processes associated with survival and longevity, including transcription and DNA repair, inflammation, glucose and lipid metabolism, oxidative stress, mitochondrial function, apoptosis, autophagy, and stress resistance. Sirtuins’ dependence on NAD⁺ allows them to function as cellular energy sensors, linking metabolic demands to selective lysine deacylation in various subcellular organelles. The aim of this review is to provide an update on this family of molecules, describing their molecular structures, physiological functions, roles in aging processes, and potential to be modulated to serve as a strategy for promoting healthy aging. Full article

Urban–industrial environments can generate mixed geogenic and traffic-related metal signatures in paediatric scalp hair, yet interpretation is challenged by left-censoring and limited health-based guidance values for hair. We quantified barium (Ba), strontium (Sr) and vanadium (V) in archived scalp hair collected in 2001 from children (6–9 years, n = 120) and adolescents (13–16 years, n = 97) residing in Alcalá de Henares (central Spain). Samples were washed, digested and quantified by Inductively coupled plasma mass spectrometry (ICP–MS; laboratory processing in 2025); results below the limit of detection (LoD) were treated as left-censored using NADA2 (no substitution). In children, Ba and Sr were frequently quantifiable (medians 0.193 and 0.412 µg/g; 38.3% and 23.3% <LoD), whereas V was heavily censored (74.2% <LoD; median 0.003 µg/g). Adolescents showed higher Ba and Sr and broader upper tails (Ba median 0.287 µg/g, P95 2.061 µg/g; Sr median 1.105 µg/g, P95 4.995 µg/g), while V remained low (median 0.011 µg/g, P95 0.052 µg/g). Ba and Sr displayed strong spatial gradients across four residential zones in adolescents (censored-data Peto–Peto tests p < 1 × 10⁻⁸), but V did not (p = 0.162). Co-located residential topsoils were available only for V and showed limited between-zone contrast; soil–hair correspondence was weak overall but moderate in adolescent girls (Spearman ρ = 0.433). These findings provide a historical baseline and support a cautious tracer-oriented interpretation in which the observed Ba–Sr spatial patterning is consistent with heterogeneous contact with dust- and traffic-influenced surface materials, while V appears less discriminatory in low-contrast community settings. Full article

Background and Objectives: Cerebral palsy is a debilitating and complex movement disorder affecting millions of people worldwide. Many children with cerebral palsy develop hip dysplasia, which can lead to pain, functional decline, and long-term complications. Regular hip surveillance is therefore essential to allow early intervention and prevent progression. At present, screening is performed manually by experienced clinicians, which can be time consuming and costly. This study aimed to compare the performance of artificial intelligence models with expert clinicians in detecting hip dysplasia in children with cerebral palsy. Materials and Methods: A thorough search of Embase, Ovid MEDLINE, and Web of Science was conducted from inception to July 2025. Studies evaluating AI-based detection of hip dysplasia in children aged 18 years or younger with cerebral palsy were included. Risk of bias was assessed using the QUADAS-2 tool. Results were synthesised narratively in accordance with SWiM guidelines. Results: Across the six included studies, which included over 4000 radiographs, AI sensitivity for detecting hip dysplasia ranged from 70% to 97.4%, and specificity ranged from 85% to 96%, depending on the migration percentage thresholds applied. Area under the curve values ranged from 0.923 to 0.999. Only one study performed external validation using a national surveillance dataset. Risk of bias was moderate to high in most studies due to internal validation and small datasets. Conclusions: The findings suggest that AI demonstrates potential as an adjunct for hip surveillance in children with cerebral palsy. Full article

Background/Aim: Dental caries is a multifactorial disease influenced by dietary habits, lifestyle factors, and host biochemical processes. Oxidative stress and advanced glycation end products (AGEs) have been implicated in oral and systemic pathophysiology, but their combined association with caries experience remains unclear. This study aimed to evaluate the relationships between caries indices, diet, smoking, oxidative stress markers, and AGEs in adults. Materials and Methods: A cross-sectional study was conducted on adults enrolled in the SALIVAGES project (2018–2020). Dental status was assessed using the DMFT index. Dietary habits and smoking status were recorded using a validated questionnaire. Oxidative stress parameters (TAC, TOS, OSI, NO, MDA, total thiols) and AGEs (FruLys, MG-H1, CML, CEL, Pyr, Arg, Lys) were quantified in saliva and plasma. Associations were analyzed using correlation tests and multivariable regression models (α = 0.05). Results: The mean DMFT was 21.89 ± 7.13, with missing teeth predominating. Caries experience was significantly associated with oxidative stress, AGEs, diet, and lifestyle. Higher decay scores were associated with increased NO and total thiols and reduced antioxidant capacity. Several salivary AGE-related biomarkers (FruLys, MG-H1, CML, and CEL) were negatively associated with the decay index. Sugary beverages, refined carbohydrates, pastries, and donuts were strongly positively associated with the decay index, whereas wholemeal bread showed an inverse association with caries indices. Smoking was independently associated with higher decay and DMFT values, corresponding to an approximately three-unit higher DMFT score. Conclusions: Caries experience in adults is associated with dietary, lifestyle, and biochemical factors. Sugar intake and smoking showed the strongest associations with caries indices, while oxidative stress parameters and selected salivary AGE-related biomarkers showed weaker but significant inverse associations with decay. These findings support preventive strategies targeting diet quality, smoking cessation, and redox balance to reduce oral disease burden. Full article

Background/Objectives: Childhood-onset Sjögren disease (cSjD) is a rare autoimmune disorder with heterogeneous manifestations and ongoing diagnostic challenges, as there are no validated paediatric criteria. Our study aims to characterise the clinical, laboratory, and imaging features of children diagnosed with cSjD at a single Romanian paediatric rheumatology centre between 2015 and 2025 and contextualise these findings within the most recent literature. Methods: A retrospective review of 15 consecutive cSjD patients was conducted, including clinical features, autoantibodies, imaging, biopsy findings, treatment, and outcomes. Results: Our cohort showed a significant female predominance (80%) and a broad age range at disease onset (3–15 years). Extraglandular manifestations were more common at presentation than glandular phenotypes (53.3% vs. 40%). Lupus-like extraglandular presentations frequently led to initial misdiagnosis as childhood-onset systemic lupus erythematosus (SLE) in our cohort. Sicca symptoms were present at diagnosis in only 3 of 15 patients (20%) and developed later during follow-up in an additional 4 patients (26.7%). Notably, the cohort included novel findings, such as an unprecedented presentation with acute exudative pericarditis complicated by cardiac tamponade. Anti-SSA antibodies and salivary gland ultrasound abnormalities were highly prevalent (86.7% and 100%, respectively). Anti-SSB antibodies were detected in seven patients (46.7%), with titres showing more variability than those of anti-SSA, ranging from just above the positivity threshold to mildly elevated levels. The association with macro-creatine kinase type I was another distinctive feature of this series. Chronic musculoskeletal pain and dryness were our patients’ most frequently reported symptoms at the last assessment, affecting up to 5/15 (33.3%) in each domain. One patient showed irreversible ocular damage during our study. Conclusions: Extraglandular presentations of cSjD are highly heterogeneous and diagnostically challenging, often occurring without glandular symptoms. Lupus-like systemic features—including facial vasculitic purpura, with or without arthralgia, and occasional pericarditis, as observed in our cohort—may contribute to frequent initial diagnostic misattribution to SLE. Early salivary gland ultrasonography, targeted autoantibody testing, and selective biopsy are essential for timely diagnosis, underscoring the urgent need for paediatric-specific validated classification criteria. Full article

Human breast milk evolves beyond simple nutrition to function as a complex signaling system that promotes neonatal development. This review analyzes the bioactive components, delineating how its specific constituents compensate for the physiological vulnerabilities of the neonate. Additionally, the distinct roles of colostral and mature milk are in fortifying the immature immune system and promoting gastrointestinal maturation. Focus is placed on the prevention of necrotizing enterocolitis, where milk oligosaccharides and microbiome function to maintain mucosal integrity and symbiosis, while preventing pathogens’ adhesion. Furthermore, how breastfeeding duration is linked to long-term metabolic and immunological programming is evaluated. MicroRNAs and bioactive lipids actively modulate gene expression and immune responses, thereby reducing the incidence of metabolic diseases and childhood malignancies. By integrating findings, this article underscores the irreplaceable role of breast milk in clinical dietetics and pediatric care. Full article

Multi-class and multi-label classification of medical dialogues remains a challenging task due to high linguistic variability and transcription noise. This study proposes an ensemble approach based on three fine-tuned Polish T5 (Text-to-Text Transfer Transformer) models trained on partially overlapping clinical dialogue datasets. The models are evaluated exclusively on low-quality, highly noisy, automatically transcribed conversations to assess real-world robustness. The results demonstrate that the ensemble of models improves classification stability and outperforms the best single model, increasing the F1-score by 21.8% for internal medicine dialogues and by 44.9% for paediatric interviews. The proposed method shows potential for practical deployment in clinical decision support and automated medical documentation systems. Full article

Despite comprehensive and multi-modal therapy, outcomes for children and adolescents with rhabdomyosarcoma (RMS) have plateaued over the past four decades. This is not for a lack of progress in the basic and translational studies of RMS. Indeed, advances in animal models and/or patient tissue sample acquisition and analysis have improved our understanding of RMS biology. Large-scale sequencing efforts have generated transcriptomic, genomic, and epigenomic datasets that highlight the heterogeneity of RMS and have the potential to improve prognostication and the application of precision medicine in patients with RMS. However, few of these discoveries have been clinically translated, and limitations to the accessibility, uniformity, and application of these new models and datasets hinder their utility. Here, we discuss how advances in understanding RMS biology, optimization of preclinical models, and strategies for translating basic science discoveries to the clinic can potentially improve outcomes for patients with RMS. Full article

This study developed and validated a stability-indicating high-performance thin-layer chromatography (HPTLC) method for the identification and quantification of gentamicin sulphate in an ointment formulation using silica gel 60 F254 HPTLC plates as the stationary phase and methanol: chloroform: ammonia solution (25%) (1:1:1, v/v/v) as the mobile phase. An ideal solvent ratio, chloroform: methanol (9:1, v/v), was used to dissolve the ointment sample before analysis. According to the guidelines of the International Council for Harmonisation (ICH), the HPTLC method was validated, demonstrating specificity by separating all three bands of gentamicin sulphate without interference from ointment excipients and/or degradation products resulting from photolytic, photolytic and oxidative, oxidative, acidic, and alkaline stress conditions. The findings of the study also revealed that the method has high levels of linearity within the range of 50–300 ng/band (R² ≥ 0.99), with detection and quantification limits of 7.10 ng, and 21.53 ng, respectively. Additionally, the method does not require any sample pre-treatment, such as extraction from the ointment base, making it simple and convenient for the quality control of gentamicin ointments. Full article

Background/Objectives: Liver function is difficult to estimate accurately. Conventional liver function tests can be normal, even in severe diseases. Dynamic liver function tests, including indocyanine green (ICG) clearance and hepatobiliary scintigraphy (HBS), are useful in adults. We aimed to evaluate the association between ICG clearance and HBS in children with liver disease and to identify liver disease markers associated with liver function measured with ICG clearance and HBS. Methods: Children aged 0–18 years followed at Copenhagen University Hospital, Rigshospitalet between November 2015 and August 2024 were eligible for inclusion if they had acute or chronic liver disease, suspected liver disease, or previous liver transplantation (LTx). All underwent ICG clearance and HBS. Results: We included 131 children with a total of 200 visits. The median visit age was 11.4 [6.6; 15.6] years. The ICG-plasma disappearance rate had the strongest correlation with the hepatic extraction fraction (ρ = 0.64, p < 0.001). ICG clearance and HBS were associated with liver injury, reduced synthetic function, cholestasis, cirrhosis, and portal hypertension, while only ICG clearance was associated with the portal blood flow. LTx was associated with increased HBS parameters, but not with ICG clearance. Conclusions: ICG clearance and HBS are correlated, and both are associated with most conventional liver function markers. This suggests their usefulness in evaluating children with liver disease. However, further evaluation of the predictive and clinical value of ICG clearance and HBS in disease progression is needed. Full article

Pulmonary hypertension (PH) is a complex condition in which early diagnosis remains challenging, particularly in patients with exertional symptoms and normal or borderline resting haemodynamics. Although right heart catheterisation is the diagnostic gold standard, transthoracic echocardiography is the recommended first-line non-invasive test. However, resting echocardiography provides only a static assessment and may underestimate disease severity in early or latent pulmonary vascular disease due to preserved pulmonary vascular compliance and adaptive right ventricular responses. Because pulmonary haemodynamics are intrinsically flow-dependent, pathological abnormalities may only emerge during increased cardiac output. Stress echocardiography, performed using exercise or pharmacological stress, enables dynamic evaluation of pulmonary pressure responses, cardiac output augmentation, right ventricular contractile reserve, and ventricular interaction. Increasing evidence indicates that stress echocardiography can unmask abnormal pulmonary pressure–flow relationships, impaired pulmonary vascular reserve, and reduced right ventricular–pulmonary arterial coupling that are not apparent at rest, thereby improving functional and haemodynamic characterisation in selected patients. This Diagnostic Review outlines the physiological basis for stress echocardiographic assessment of pulmonary circulation, proposes practical recommendations for patient selection and testing protocols, and provides a framework for interpretation centered on pressure–flow relationships rather than absolute pulmonary pressure thresholds. Particular attention is given to clinical scenarios with high diagnostic yield, including unexplained exertional dyspnoea, systemic sclerosis, suspected heart failure with preserved ejection fraction, at-risk relatives of patients with pulmonary arterial hypertension, selected athletes, and paediatric populations. Stress echocardiography should not be considered a standalone diagnostic test for PH but, when performed in experienced centers and integrated within structured diagnostic pathways, it represents a valuable non-invasive adjunct to guide referral for invasive haemodynamic confirmation. Full article

Sudden Infant Death Syndrome (SIDS) continues to be one of the most challenging and tragic causes of infant mortality in developed countries. While public health interventions have reduced its prevalence, the underlying mechanisms contributing to SIDS remain largely unclear. The biological basis of SIDS is widely believed to be multifactorial in nature, involving inherited genetic vulnerabilities, including mutations in cardiac ion channels and genes associated with brainstem serotonin function, metabolic enzymes, and inflammatory mediators. This review presents a comprehensive analysis of genetic studies relating to SIDS, incorporating recent findings from molecular autopsies, genome-wide association studies and functional assays. It also explores how gene–environment interactions, polygenic risk scores, and multi-omic strategies are reshaping our understanding of this complex condition. The review aims to integrate recent insights from molecular autopsy, genomic profiling, and gene–environment interactions to offer a framework for better risk assessment and the stratification of vulnerable infants who could benefit from targeted clinical and public health interventions. Full article

Background/Objectives: The Mitrofanoff appendicovesicostomy (MAV) is the gold standard for creating a continent catheterizable channel in children unable to perform clean intermittent catheterization (CIC) through the native urethra. Minimally invasive surgery has progressively replaced open techniques in pediatric urology, offering improved recovery and favorable cosmetic outcomes, and robotic-assisted Mitrofanoff has gained popularity in recent years. However, the high costs and limited availability of robotic systems create disparities in access to pediatric urologic reconstruction, particularly in low- and middle-income countries. In this context, the laparoscopic Mitrofanoff (MAV-L) and the laparoscopic-assisted Mitrofanoff (MAV-LA) represent practical, cost-effective alternatives, valuable in institutions without robotic platforms or in resource-limited settings. Recent evidence demonstrates that advanced laparoscopic approaches remain feasible even for complex urological procedures, supporting their continued relevance in the robotic era. Methods: We conducted a retrospective case series including seven male children (aged 9–12 years) who underwent MAV between 2018 and 2023. Peri-operative data included demographics, operative time, length of hospitalization, and complications. Functional and aesthetic outcomes were assessed during long-term follow-up. Statistical analysis accounted for the small sample size by using non-parametric tests where appropriate. Results: Three patients (43%) underwent MAV-L and four (57%) MAV-LA. Mean operative time appeared longer in MAV-L (273.3 ± 20.5 min) than in MAV-LA (203.8 ± 24.3 min; exploratory p = 0.019). Hospital stay was 9 ± 0.8 days vs. 7.5 ± 0.5 days (p = 0.026). During follow-up (43.3 ± 10.9 vs. 26.3 ± 5.4 months; p = 0.034), two complications occurred, both in the MAV-L group (stomal stenosis and channel leakage). All patients reported excellent continence, ease of catheterization, and high cosmetic satisfaction. Conclusions: Both laparoscopic and laparoscopic-assisted Mitrofanoff techniques are safe, feasible, and effective in children. Favorable cosmetic satisfaction was reported in the fully laparoscopic subgroup, based on subjective assessment. Importantly, these laparoscopic techniques are sustainable alternatives to robotic surgery, offering accessibility and high-quality reconstructive care even in centers with limited financial and technological resources. Full article

Elizabethkingia species are rare but increasingly recognised Gram-negative pathogens linked to healthcare-associated transmission, intrinsic multidrug resistance, and severe infection in vulnerable hosts. We performed a comprehensive review of human Elizabethkingia infections by systematically searching PubMed on 18 October 2025 and included English-language case reports, case series, and outbreak investigations; species were analysed as reported (legacy nomenclature retained), and adults were defined as ≥18 years. In total, 374 studies were included (300 case reports, 41 case series, 33 outbreak investigations). Adult infections were predominantly healthcare-related, affected older adults with substantial comorbidities and most often presented as bacteraemia or sepsis and pneumonia; crude mortality in adult case reports was 32.8%. Paediatric disease was concentrated in neonates and Neonatal Intensive Care Unit (NICU) settings, with meningitis and bloodstream infection predominating; crude mortality in paediatric case reports was 23.3%, and neurological sequelae were frequently reported among survivors. Across studies, isolates showed broad resistance to β-lactams and near-universal resistance to carbapenems, with variable activity to fluoroquinolones and trimethoprim–sulfamethoxazole and more consistent in vitro activity to minocycline. Species misidentification (notably Elizabethkingia anophelis as Elizabethkingia meningoseptica) and heterogeneous susceptibility testing limited comparability. Outbreak investigations repeatedly implicated water-associated reservoirs and reusable equipment, underscoring the need for improved diagnostics, susceptibility-guided therapy and water-focused infection prevention. Full article

Introduction: Fever is one of the most common reasons for Paediatric Emergency Department (PED) visits, often driven by parental anxiety and misconceptions about fever management. This study aimed to evaluate the knowledge, attitudes, and practices of parents regarding childhood fever to identify gaps and guide targeted educational interventions. Understanding parental behaviors is crucial for improving care outcomes and reducing unnecessary PED utilization. Methods: This study is a descriptive cross-sectional study. The sample of this study consists of a total of 440 parents of children admitted to the Paediatric Emergency Department (PED) with complaints of fever. Convenience sampling was used to select the participants. Data were collected using a questionnaire covering sociodemographics, a form surveying the parents’ fever knowledge and attitude, and the validated parents’ fever management scale (Turkish version). The data were analyzed using the SPSS 22.0 statistical program. Results: Most parents (95.5%) reported prior experience with childhood fever, yet 54.1% lacked a regular physician. Common fever detection methods included tactile assessment (56.4%) and thermometers (27.3%). Parental concern arose at 39 °C (48.6%). Cold applications (41.6%) and antipyretics (21.1%) were frequent interventions. The mean PFMS-TR score was high (34.97 ± 4.27), indicating elevated caregiver burden. Scores varied significantly by the child’s age (higher for infants, p = 0.044) and maternal education (higher for educated mothers, p = 0.008). Satisfaction with healthcare staff correlated with higher scores (p = 0.024). Negative correlations emerged between parental age, number of children, and fever management scores (p < 0.05). Conclusions: Parents exhibited high interventionist behaviors and persistent knowledge gaps, underscoring the need for targeted education programs. Educational programs targeting fever management, tailored to parental demographics and misconceptions, are essential. Healthcare providers, particularly pediatric nurses, should prioritize clear communication and evidence-based guidance to empower parents and reduce unnecessary healthcare burdens. Future research should expand to diverse geographic and cultural settings to enhance generalizability. Full article