Search Results (8,991)

A series of 6:2 fluorotelomer ethoxylates (FTEOs) has been recently detected in human serum. Whether it has the potential to disrupt lipid metabolism in human populations remains largely unexplored. This study quantified serum concentrations of 6:2 FTEOs in 237 healthy Chinese adults, examined the gender- and age-specific differences in serum levels of 6:2 FTEOs, and investigated the associations between serum levels of 6:2 FTEOs and lipid profiles for the first time. Nine 6:2 FTEO homologues were detected in collected human serum, with detection frequencies of 22–81%. 6:2 FTEO8 and 6:2 FTEO9 were the more abundant 6:2 FTEO homologues in human serum, displaying the mean levels of 0.69 ng/mL (range < LOD–7.36 ng/mL) and 0.71 ng/mL (<LOD–8.12 ng/mL), respectively. Male participants had much higher (p < 0.05) mean serum levels of 6:2 FTEO6 (0.61 vs. 0.31 ng/mL), 6:2 FTEO7 (0.44 vs. 0.21 ng/mL), 6:2 FTEO8 (0.91 vs. 0.38 ng/mL), and 6:2 FTEO11 (0.35 vs. 0.18 ng/mL) than female subjects. Correlation analysis revealed a significantly positive relationship (p < 0.01) between the age of participants and human serum concentrations of 6:2 FTEO6–6:2 FTEO11. Multivariate linear regression identified significant positive associations between specific 6:2 FTEO homologues (e.g., 6:2 FTEO6, 6:2 FTEO8–6:2 FTEO10) and elevated total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride levels. Full article

Background: Thallium is a metal that is ubiquitous in our natural environment. Despite its potential for high toxicity, thallium is understudied and not regulated in food. The California Department of Public Health was alerted to a household cluster of elevated urine thallium levels noted among a mother (peak 5.6 µg/g creatinine; adult reference: ≤0.4 µg/g creatinine) and her three young children (peak 10.5 µg/g creatinine; child reference: ≤0.8 µg/g creatinine). Objectives: This case report identifies questions raised after a public health investigation linked a household’s thallium exposure to a commercially available food product. We provide an overview of the public health investigation. We then explore concerns, such as gaps in toxicological data and limited surveillance of thallium in the food supply, which make management of individual and population exposure risks challenging. Methods: We highlight findings from a cross-agency investigation, including a household exposure survey, sampling of possible environmental and dietary exposures (ICP-MS analysis measured thallium in kale chips at 1.98 mg/kg and 2.15 mg/kg), and monitoring of symptoms and urine thallium levels after the source was removed. We use regulatory and research findings to describe the challenges and opportunities in characterizing the scale of thallium in our food supply and effects of dietary exposures on health. Discussion: Thallium can bioaccumulate in our food system, particularly in brassica vegetables like kale. Thallium concentration in foods can also be affected by manufacturing processes, such as dehydration. We have limited surveillance data nationally regarding this metal in our food supply. Dietary reviews internationally show increased thallium intake in toddlers. Limited information is available about low-dose or chronic exposures, particularly among children, although emerging evidence shows that there might be risks associated at lower levels than previously thought. Improved toxicological studies are needed to guide reference doses and food safety standards. Promising action towards enhanced monitoring of thallium is being pursued by food safety agencies internationally, and research is underway to deepen our understanding of thallium toxicity. Full article

Background: Empowerment during pregnancy is linked to improved maternal and infant health outcomes and greater maternal well-being. Group Antenatal Care (GANC), a participant-centered model of care, promotes empowerment, active engagement, and the deconstruction of hierarchy between participants and care providers. It combines health assessment, interactive learning, and community building. While empowerment is a core concept of GANC, the ways it manifests and the elements that facilitate it remain unclear. Method: We conducted a generic qualitative study across four organizations in Brussels, using multiple data collection methods. This included interviews with 13 participants and 21 observations of GANC sessions, combining both the insider and outsider perspective. An adapted version of the Pregnancy-Related Empowerment Scale (PRES) guided the interviews guide and thematic analysis. Results: We identified seven themes that capture how empowerment occurs in GANC: peer connectedness, provider connectedness, skillful decision-making, responsibility, sense of control, taking action, and gaining voice. Several aspects of GANC contribute to empowerment, particularly the role of facilitators. Conclusions: This study highlights how GANC enhances empowerment during pregnancy through interpersonal, internal, and external processes. Important components within GANC that support this process include the group-based format and the interactive nature of the discussions. The presence of skillful GANC facilitators is an essential prerequisite. In a diverse and often vulnerable context like Brussels, strengthening empowerment through GANC presents challenges but is especially crucial. Full article

Background and Objectives: Exclusive breastfeeding offers optimal nutrition and health benefits for infants, yet many mothers face challenges that impact their ability to breastfeed. This study aimed to explore breastfeeding practices among Romanian mothers and identify factors associated with successful exclusive breastfeeding. Materials and Methods: A cross-sectional online survey was conducted from February to March 2025, targeting Romanian mothers via social media platforms. The questionnaire, developed specifically for this study, collected data on sociodemographics, birth and neonatal variables, hospital practices, feeding intentions, community influences, and breastfeeding outcomes. A total of 874 valid responses were analyzed using Fisher’s exact tests and multivariable logistic regression. Results: While 87.2% of mothers intended to breastfeed, only 56.1% reported exclusive breastfeeding. Factors significantly associated with reduced likelihood of exclusive breastfeeding included maternal age ≥ 30 years (OR = 1.40, p = 0.042), Cesarean delivery (OR = 1.78, p < 0.001), absence of rooming-in (OR = 2.32, p < 0.001), and pacifier use (OR > 4.7, p < 0.001). Protective factors included non-smoking status (OR = 0.52, p < 0.001) and encouragement to breastfeed by medical staff (OR = 1.60, p = 0.004). Despite external advice to use formula, many mothers continued breastfeeding. Conclusions: Although breastfeeding intention was high, exclusive breastfeeding remains suboptimal in Romania. Targeted support—particularly in maternity hospitals and for mothers recovering from Cesarean sections—alongside prenatal education and consistent postnatal guidance are essential to bridge the gap between intention and practice. Full article

In humans, the master circadian clock, present in the suprachiasmatic nucleus, plays an important role in controlling life-sustaining functions. The development of the circadian clock begins in the fetal period and is almost completed during infancy to early childhood, based on the developmental program that is influenced by the mother’s daily rhythms and, after birth, with the addition of information from the daily life environment. It is known that circadian rhythms are deeply related not only to the balance of a child’s mental and physical development but also to maintaining mental and physical health throughout one’s life. However, it has been suggested that various health problems in the future at any age may be caused by the occurrence of circadian disturbances transmitted by the mother during the fetal period. This phenomenon can be said to support the so-called DOHaD theory, and the involvement of the mother in the maturation of appropriate and stable circadian rhythms cannot be ignored. We consider the problems and countermeasures during the fetal and infant periods, which are important for the formation of circadian clocks. Full article

Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no crescents on histopathology (Group 1) and 364 with crescentic nephritis (Group 2). Collected data included clinical features, lab indicators, histopathological grading, and factors causing glomerular sclerosis. Logistic regression was used to assess factors affecting crescent formation in IgAVN. Double-immunofluorescence assay was used to detect TGF-β1, MCP-1, α-SMA, Collagen I, and FN1 in kidney biopsy specimens. The relationship between kidney fibrosis factors and histopathological grade were analyzed using Chi-square and Pearson tests. Results: A total of 741 patients with IgAVN were included in the study. Univariate logistic regression identified potential factors related to crescent formation, including age, gender, clinical classification, hematuria grade, 24 h urine protein level, peripheral white blood cells (WBCs), serum albumin, Cystatin-C, APTT, and PT. Multivariate analysis revealed statistical significance for age, 24 h urine protein, and WBCs across pathological grades (p < 0.05). Mantel–Haenszel Chi-square tests indicated a linear relationship between IgAVN pathological grade and α-SMA, TGF-β1, MCP-1, and FN1. Pearson correlation analysis confirmed a positive correlation between pathological grade and these markers. Conclusions: Age, 24 h urinary protein, and blood WBCs are identified as risk factors for histopathological crescent formation in children with IgAVN. Additionally, a higher pathological grade is associated with more pronounced fibrosis indicators. Full article

The COVID-19 pandemic was a profoundly influential global occurrence in recent history, impacting daily life, economics, and healthcare systems for an extended period. The abundance of data has been essential in creating models to simulate and forecast the dissemination of infectious illnesses, aiding governments and health organizations in making educated decisions. This research primarily focuses on designing a control technique that incorporates the five most important inputs that impact the spread of COVID-19 on the Romanian territory. Quantitative analysis and data filtering are two crucial aspects to consider when developing a mathematical model. In this study the transfer function principle was used as the most accurate method for modeling the system, based on its superior fit demonstrated in a previous study. For the control strategy, a PI (Proportional-Integral) controller was designed to meet the requirements of the intended behavior. Finally, it is showed that for such complex models, the chosen control strategy, combined with fine tuning, led to very accurate results. Full article

Background/Objective: This study explores a novel approach for diagnosing common middle ear pathologies using Pressure-Less Acoustic Immittance (PLAI™), a non-invasive alternative to conventional tympanometry. Methods: A total of 516 ear measurements were collected and stratified into three age groups: 0–3, 3–12, and 12+ years, reflecting key developmental stages. PLAI™-derived acoustic parameters, including resonant frequency, peak admittance, canal volume, and resonance peak frequency boundaries, were analyzed using Random Forest classifiers, with SMOTE addressing class imbalance and SHAP values assessing feature importance. Results: Age-specific models demonstrated superior diagnostic accuracy compared to non-stratified approaches, with macro F1-scores of 0.79, 0.84, and 0.78, respectively. Resonant frequency, ear canal volume, and peak admittance consistently emerged as the most informative features. Notably, age-based stratification significantly reduced false negative rates for conditions such as Otitis Media with Effusion and tympanic membrane retractions, enhancing clinical reliability. These results underscore the relevance of age-aware modeling in pediatric audiology and validate PLAI™ as a promising tool for early, pressure-free middle ear diagnostics. Conclusions: While further validation on larger, balanced cohorts is recommended, this study supports the integration of machine learning and acoustic immittance into more accurate, developmentally informed screening frameworks. Full article

Background: Neurogenic bladder (NB) in children may lead to recurrent urinary tract infections (UTIs), renal deterioration, and a reduced quality of life. Clean intermittent catheterization (CIC) is the standard of care, but in some patients, CIC may be unfeasible due to anatomical, sensory, or compliance issues. Button cystostomy (BC) has emerged as a minimally invasive, bladder-preserving alternative. This study aimed to assess the feasibility, safety, and outcomes in the long-term of BC in pediatric NB patients. Methods: Retrospective analysis was conducted on children with NB who underwent endoscopic BC placement between January 2020 and December 2024 in a tertiary pediatric center. Demographic data, operative time, complications, and follow-up outcomes were collected. All procedures used an endoscopic approach with cystoscopic guidance for safe device placement. Results: Thirty-three patients (25 males; median age 7.96 years) underwent BC placement. Most had spinal dysraphism (63.6%). The mean operative time was 48.5 ± 6 min. During a mean follow-up of 2.1 ± 1.4 years, five patients (15.2%) had febrile UTIs and two had minor leakage. No major complications occurred. Four buttons were removed due to clinical improvement (N = 1), the fashioning of a continent derivation (N = 1) and implantation of a sacral neuromodulator (N = 2); two patients accepted CIC. Satisfaction was reported by 93.9% of families. Conclusions: BC is an effective, minimally invasive alternative for urinary drainage in children with NB, even when compared to continent diversion techniques such as the Mitrofanoff, due to its lower invasiveness, greater feasibility, and lower complication rate. Broader adoption may be warranted, but prospective studies are needed to confirm long-term outcomes. Full article

The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article

Metro carriages, as enclosed transport microenvironments, have been understudied regarding pollution characteristics and health risks from ACs, especially during high-temperature summers that amplify exposure. This study applied NTS techniques for the first time across three major Chengdu metro lines, systematically identifying sixteen ACs, including hazardous species such as acetophenone, benzonitrile, and benzoic acid that are often overlooked in conventional BTEX-focused monitoring. The TAC concentration reached 41.40 ± 5.20 µg/m³, with half of the compounds exhibiting significant increases during peak commuting periods. Source apportionment using diagnostic ratios and PMF identified five major contributors: carriage material emissions (36.62%), human sources (22.50%), traffic exhaust infiltration (16.67%), organic solvents (16.55%), and industrial emissions (7.66%). Although both non-cancer (HI) and cancer (TCR) risks for all population groups were below international thresholds, summer tourists experienced higher exposure than daily commuters. Notably, child tourists showed the greatest vulnerability, with a TCR of 5.83 × 10⁻⁷, far exceeding that of commuting children (1.88 × 10⁻⁷). Benzene was the dominant contributor, accounting for over 50% of HI and 70% of TCR. This study presents the first integrated NTS and quantitative risk assessment to characterise ACs in summer metro environments, revealing a broader range of hazardous compounds beyond BTEX. It quantifies population-specific risks, highlights children’s heightened vulnerability. The findings fill critical gaps in ACs exposure and provide a scientific basis for improved air quality management and pollution mitigation strategies in urban rail transit systems. Full article

The perianal skin is a unique “skin–gut” boundary that serves as a critical hotspot for the exchange and evolution of antibiotic resistance genes (ARGs). However, its role in the dissemination of antimicrobial resistance (AMR) has often been underestimated. To characterize the resistance patterns in the perianal skin environment of patients with perianal diseases and to investigate the drivers of AMR in this niche, a total of 51 bacterial isolates were selected from a historical strain bank containing isolates originally collected from patients with perianal diseases. All the isolates originated from the skin site and were subjected to antimicrobial susceptibility testing, whole-genome sequencing, and co-occurrence network analysis. The analysis revealed a highly structured resistance pattern, dominated by two distinct modules: one representing a classic Staphylococcal resistance platform centered around mecA and the bla operon, and a broad-spectrum multidrug resistance module in Gram-negative bacteria centered around tet(A) and predominantly carried by IncFIB and other IncF family plasmids. Further analysis pinpointed IncFIB-type plasmids as potent vehicles driving the efficient dissemination of the latter resistance module. Moreover, numerous unexplained resistance phenotypes were observed in a subset of isolates, indicating the potential presence of emerging and uncharacterized AMR threats. These findings establish the perianal skin as a complex reservoir of multidrug resistance genes and a hub for mobile genetic element exchange, highlighting the necessity of enhanced surveillance and targeted interventions in this clinically important ecological niche. Full article

Background: North Carolina Macular Dystrophy (NCMD) is a non-progressive inherited macular dystrophy characterized by marked phenotypic variability. The genetic etiology of NCMD remains largely unknown, and only a limited number of families have been reported in Europe. Methods: We performed an in-depth investigation of an Italian family affected by NCMD using an integrated approach that combined SNP-array analysis, whole-exome sequencing, and long-read whole-genome sequencing. Additionally, we conducted a comprehensive review of NCMD-related literature. Results: We identified a novel 98 Kb duplication involving both PRDM13 and CCNC genes in a three-generation kindred, where the proband exhibited severe macular alterations, while all other affected family members presented with a milder clinical phenotype. A review of the literature suggests different genotype–phenotype correlations and similar penetrance for duplications and single-nucleotide variants (SNVs) in described families. Specifically, smaller duplications may be associated with more severe phenotypes, while SNVs exhibit high phenotypic variability. Conclusions: In this study, we describe the first NCMD Italian family, in which the integration of second- and third-generation sequencing methods enabled the identification of a novel pathogenic PRDM13 and CCNC duplication, thereby expanding the mutational spectrum of NCMD. Overall, these findings, together with the literature review, highlight the importance of selecting appropriate genetic testing approaches that allow the detection of non-coding variants and CNVs and thus enable accurate diagnosis and effective clinical management of patients and their families. Full article

Background: More than 1500 genes are associated with developmental delay and intellectual disability, with variants in many of these genes contributing to a shared phenotype. The discovery of variants of uncertain significance (VUS) found in these genes during genetic testing can lead to ambiguity and further delay in diagnosis and medical management. Phenotyping, additional genetic testing, and functional studies can all add valuable information to help reclassify these variants. Here we demonstrate the clinical utility of epigenetic signatures in prioritizing variants of uncertain significance in genes associated with developmental delay (DD) and intellectual disability (ID). Methods: Genome sequencing was performed in a male with developmental delay. He was found to have VUSs in both PHF6 and DDB1 genes, linked with Börjeson–Forssman–Lehmann syndrome (BFLS) and White–Kernohan syndrome (WHIKERS), respectively. These two disorders share a similar phenotype but have distinct inheritance patterns and molecular pathogenic mechanisms. DNA methylation profiling (DNAm) of whole blood was performed using the clinically validated EpiSign assay. Results: The proband’s methylation profile demonstrated a strong correlation with the BFLS methylation signature, supporting the PHF6 variant as a likely cause of his neurodevelopmental disorder. Conclusions: Epigenetic testing for disorders with distinct methylation patterns can provide diagnostic utility when a patient presents with variants of uncertain significance in genes associated with developmental delay. Epigenetic signatures can also guide genetic counselling and family planning. Full article