Search Results (1,478)

Background/Objectives: Pediatric palliative care seeks to relieve suffering and improve the quality of life of children with severe conditions and their families. This prospective cohort study assessed changes in quality of life following enrollment in a pediatric palliative care program at a tertiary care center in Mexico and explored factors associated with these changes. Methods: Children with life-limiting or severe disabling conditions were followed at baseline, 3 months, and 6 months. Quality of life was measured using the Pediatric Quality of Life Inventory (PedsQL™) Cancer Module for oncologic patients and the PedsQL™ Family Impact Module for all families. Results: A total of 166 families completed the Family Impact Module questionnaires, and 116 oncologic patients completed the Cancer Module. Mean children’s PedsQL Cancer Module scores improved from 58.9 to 77.9, and family scores improved from 60.1 to 78.8 over six months (both p < 0.001). Families of oncologic patients and those residing outside the Mexico City metropolitan area had lower baseline scores (adjusted differences −9.84, 95% CI: −15.9 to −3.77; and −6.9, 95% CI: −12.38 to −1.44, respectively); however, the latter group showed a greater rate of improvement over time, contrary to our initial hypothesis—survival varied by diagnosis, with longer survival observed in children with neurologic or intracranial conditions. Conclusions: The quality of life of families and pediatric oncologic patients showed improvement over time following enrollment in a specialist pediatric palliative care program in a middle-income setting. Equitable access should be ensured for families affected by chronic conditions, particularly those living beyond major urban areas. Full article

Background/Objectives: Alzheimer’s disease (AD) exhibits high heritability (60–80%), yet individual-level genetic risk prediction remains challenging. While APOE ε4 is the strongest genetic risk factor, incomplete penetrance complicates risk assessment. Methods: We analyzed seven blood-related members across three generations using the Korean Chip v2.0 genotyping (~1.2 M SNPs) and Illumina EPICv2 DNA methylation profiling. Genetic burden score (GBS) was calculated by summing risk alleles across 320 variants in six AD-associated genes (APOE, PICALM, CLU, CR1, BIN1, and ABCA7). Results: An unexpected pattern was observed in this family: the affected individual (J-003) had the lowest GBS (39 alleles), while individuals with higher genetic burden (51–61 alleles) remained cognitively healthy. J-003 also exhibited lower APOE methylation (β = 0.495) compared to the family mean (β = 0.523). CR1 contributed the most risk alleles across the family, followed by PICALM. Conclusions: This single-case observation cannot establish causality, generalizability, or biological significance. The affected individual’s lower APOE methylation may represent a causal factor, disease consequence, or coincidental variation—scenarios that cannot be distinguished from this dataset. Validation in larger cohorts with multiple affected individuals is required to determine whether integrated multi-omics approaches can inform personalized risk assessment in familial contexts. Full article

Francophone populations outside Quebec were disproportionately affected by the COVID-19 crisis. Despite French being one of Canada’s official languages, access to information and services in French remains limited. This study examined Francophone families’ (FF) post-pandemic health and well-being needs (PPHW) in the Canadian Prairie provinces. An online survey assessed PPHW needs among 319 FF in Alberta (AB), Saskatchewan (SK), and Manitoba (MB). Respondents ranked PPHW needs from a predefined list; logistic regression analyzed socio-demographic influences. Divided into AB/SK and MB cohorts, sociodemographic profiles were statistically distinct for many variables, but with similarities found in gender of respondents (women: 73% in AB/SK, 79% in MB), marital status (married: 81% in AB/SK, 88% in MB), area of residence (urban: 86% in AB/SK, 81% in MB), and number of children (2 children: 49% in AB/SK, 41% in MB). Three high-priority needs were shared across provinces: (1) access to recreational, athletic, and artistic activities in French for children (variations by child gender); (2) access to French healthcare professionals (variations by education level and language difference); and (3) social activities in French for families. AB/SK respondents prioritized mental health services in French for adults and youth. MB families prioritized belonging to a Francophone community (variations by gender of children) and education services in French (variations by age of children). Understanding these common and province-specific priorities can inform policy and service planning. Full article

Background and Objectives: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive, heterogeneous, and lethal human malignancies, underscoring the urgent need for novel, targeted therapeutic strategies for neo(adjuvant) individualized treatment. The epidermal growth factor receptor family (ErbB) is directly involved in abnormal cell proliferation and tumor growth. The overexpression and amplification of HER2 and HER3 have emerged as key molecular events in pancreatic ductal adenocarcinoma. The aim of this study was to evaluate these membrane receptors’ overexpression in relation to pTNM staging, perineural and lymphovascular invasion, and tumor volume in order to obtain the immunohistochemical profile and enhance the development of a targeted and personalized therapy. Materials and Methods: An observational analytical cohort study included patients with histopathologically naïve, confirmed PDAC who underwent cephalic pancreatoduodenectomy at a national high-volume referral center between 2017 and 2022. Archived surgical specimens were retrieved and examined using a tissue microarray technique in two separate pathology departments by two independent pathologists. Results: HER2 positivity was found in 25 cases, of which 84% had lymphatic invasion, 50% had vascular invasion, and 84% had perineural invasion. Patients with HER3 positivity had lymphatic invasion (82.5%), perineural invasion (79.4%), and vascular invasion (38.1%). Combined HER2 and HER3 positivity was present in 19 cases, and these patients had 84.2% perineural invasion. Conclusions: HER2 and HER3 overexpression often coexisted with pathological features, such as perineural invasion, in cases of combined HER2 and HER3 positivity. These findings support the involvement of the ErbB receptor family in pancreatic carcinogenesis and suggest their potential as targets for future (neo)adjuvant therapeutic strategies. Full article

This study investigates the demographic transformation of Spain’s settlement system from 2000 to the present, driven by intersecting forces of rural depopulation, metropolitan concentration, immigration, and welfare-state dynamics. Building on an integrated theoretical framework that combines Maslow’s hierarchy of needs, demographic accounting, territorial carrying capacity, and spatial centrality, the research aims to (1) identify the mechanisms governing population redistribution across Spanish municipalities, and (2) simulate future demographic trajectories under current policy regimes. Key findings reveal that all net population growth since 2000 stems exclusively from immigration and its demographic sequelae, while the native Spanish cohort has experienced a net decline of 5.5 million due to negative natural change. The analysis further uncovers a self-reinforcing “demographic trap,” wherein welfare eligibility tied to household size incentivizes higher fertility among economically vulnerable immigrant groups, even as native families delay childbearing due to economic precarity. These dynamics are accelerating a process of “territorial transmutation,” projected to culminate in a shift in de facto governance by 2045. The study concludes that immigration alone cannot reverse rural depopulation or ensure fiscal sustainability without structural reforms to welfare design, territorial incentives, and demographic foresight. Full article

Background/Objectives: Male breast cancer (MBC) is rare, accounting for less than 1% of all breast cancers. Given its low incidence, male breast cancer (MBC) remains understudied; this 33-year Serbian cohort was assessed for clinicopathological features, therapeutic approaches, genetic alterations, and survival. Methods: We retrospectively analyzed MBC patients diagnosed between 1991 and 2024 at the Institute for Oncology and Radiology of Serbia. Data included demographics, tumor characteristics, and stage, treatment, hormone receptor and HER2 status, Ki-67 index, genetic testing, and survival. Results: A total of 191 patients were identified (median age 66). Family history was negative in 91% and positive in 5.8%. T2 tumors were most frequent (36%), and 96% presented without metastasis. Mastectomy with axillary or sentinel lymph node dissection was performed in 78.5%. Neoadjuvant chemotherapy and radiotherapy were administered in 5.8% and 8.4%. Estrogen receptor positivity was 72%, progesterone receptor 88%, HER2 overexpression 11.0%, and triple-negative tumors 2.6% (40% with axillary involvement). High Ki-67 (≥15%) was recorded in 28.8%. Adjuvant chemotherapy, radiotherapy, and hormone therapy were given in 36%, 58%, and 68%. Among 37 genetically tested patients, seven had pathogenic variants (BRCA1, BRCA2, CHEK2, PALB2). Disease recurrence occurred in 30%. Median follow-up was 53 months. Median disease-free survival (DFS) was 82 months (1-, 2-, 5-, 10-year DFS: 87%, 73%, 57%, 39%). Median overall survival (OS) 131 months (1-, 2-, 5-, 10-year OS: 95%, 93%, 73%, 53%). Conclusions: This long-term cohort highlights the predominance of hormone-receptor positivity, the infrequency of germline mutations, and moderate survival rates, informing patient management and guiding future studies. Full article

Background: Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental condition influenced by both genetic and non-genetic factors, although the underlying pathomechanisms remain unclear. We systematically analyzed microRNA (miRNA) expression and associated functional pathways in ASD to evaluate their potential as prenatal/postnatal, diagnostic, and prognostic biomarkers. Methods: Peripheral blood mononuclear cells from 12 Sicilian patients with ASD (eight with normal cognitive function) and 15 healthy controls were analyzed using small RNA sequencing. Differential expression analysis was performed with DESeq2 (|fold change| ≥ 1.5; adjusted p ≤ 0.05). Functional enrichment and network analyses were conducted using Ingenuity Pathway Analysis, focusing on Diseases and Biofunctions. Results: 998 miRNAs were differentially expressed in ASD, 424 upregulated and 553 downregulated. Enriched pathways were primarily associated with psychological and neurological disorders. Network analysis highlighted three principal interaction clusters related to inflammation, cell survival and mechanotransduction, synaptic plasticity, and neuronal excitability. Four miRNAs (miR-296-3p, miR-27a, miR-146a-5p, and miR-29b-3p) emerged as key regulatory candidates. Conclusions: The marked divergence in miRNA expression between ASD and controls suggests distinct regulatory patterns, thus reinforcing the central involvement of inflammatory, autoimmune, and infectious mechanisms in ASD, mediated by miRNAs regulating S100 family genes, neuronal migration, and synaptic communication. However, rather than defining a predictive biomarker panel, this study identified candidate miRNAs and regulatory networks that may be relevant to ASD pathophysiology. As such, further validation in appropriately powered cohorts with predictive modeling frameworks are warranted before any biomarker or diagnostic implications can be inferred. Full article

Background: A childhood burn presents new and unfamiliar challenges to patients and their parents during recovery. These injuries can negatively impact activities such as independence in self-care, participation in physical activity, and social interaction. As such, pediatric burn patients are at risk of poorer quality of life (QoL) outcomes after their burn. In this longitudinal, observational cohort study, we examined the social, demographic, and clinical factors that were associated with a poor QoL at 12 months postburn for pediatric patients aged > 2 years with non-severe burns in Western Australia. Methods: Inpatients were recruited from the pediatric burn unit at Perth Children’s Hospital in Western Australia between February 2021 and September 2022. Demographic and family information (age, sex, postcode, parental education, languages spoken at home) and clinical data (burn cause, TBSA%, location, surgical interventions, length of stay) were collected at baseline. At 6 and 12 months, caregivers completed the Brisbane Burn Scar Impact Profile (BBSIP). Results: A total of 37 caregivers completed the Brisbane Burn Scar Impact Profile (BBSIP). For the child’s QoL, 57% of caregivers reported that some impact remained for overall QoL, 32% for sensory intensity, 46% for sensitivity, 22% for daily living (22%), and 19% for emotional reactions. Parent worry was impacted in 46% of caregivers. Being female was associated with greater long-term impacts, particularly in overall functioning and parental worry. The burn location also influenced outcomes, with injuries to the upper limbs linked to higher sensory intensity and emotional impact. Children from culturally and linguistically diverse (CaLD) backgrounds, indicated by those speaking a language other than English at home (LOTE), demonstrated significantly greater effects across several domains, including overall impact, daily living, appearance, and parent worry. Conclusions: A substantial proportion of children continued to experience impacts from non-severe burns across multiple domains, indicating that even small-area burns can have lasting effects. The factors associated with worse scores were the child being female, the families being linguistically diverse, and upper body burns. Full article

Deleterious variants in SCN5A lead to a wide clinical spectrum that includes pathologies characterized by life-threatening cardiac events (CEs). In the pediatric population, early identification, management, and risk stratification of these pathologies are the main current challenges. This study analyzed a Spanish pediatric cohort (≤18 years) carrying rare SCN5A variants to explore genotype–phenotype correlations. A retrospective descriptive cohort study, including clinical, demographic, and genetic data of probands and their relatives, was conducted. Out of 100 children studied, 69 had definitively deleterious SCN5A variants (26 females, 38%; median age: 3 years, IQR 1–12). The main diagnoses were isolated Brugada syndrome (BrS) (31; 45%); isolated long QT syndrome type 3 (LQT3) (5; 7%); isolated progressive cardiac conduction disease (PCCD) (1; 2%); isolated familial atrial fibrillation (1; 2%); overlapping phenotypes (7; 10%) including: BrS-PCCD (2; 2.8%); BrS-LQT3 (1; 1.4%); premature ventricular contraction-dilated cardiomyopathy (1; 1.4%); BrS-LQT3-PCCD (1; 1.4%); BrS-PCCD-sick sinus syndrome (SSS) (1; 1.4%) and BrS-PCCD-SSS-familial atrial fibrillation (1; 1.4%). Of them, 13 (19%) patients presented with CEs (cardiogenic syncope, ventricular tachycardia/fibrillation, sudden cardiac arrest/death, and appropriate implantable cardio defibrillator shock). These findings underscore the utility of genetic testing for early diagnosis, risk stratification, and personalized management, enhancing preventive strategies for CE prevention in pediatrics. Full article

Background/Objectives: Advances in the genetic understanding of pheochromocytoma–paraganglioma (PPGL) have considerably refined personalized approaches to diagnosis and management. This study aims to present our institutional experience on the diagnostic characteristics, clinical course, and genetic background of patients with PPGL, in the context of the current literature. Methods: This retrospective analysis included 35 patients diagnosed with PPGL between years 2020 and 2024, all of whom underwent surgical resection and next-generation sequencing for germline mutations in major PPGL susceptibility genes. Clinical presentation, biochemical profile, pathological findings, and follow-up outcomes were compared between mutation-positive and mutation-negative cases. Results: Of the 35 patients with PPGL, germline mutations were identified in 6 patients (17%): 2 in Cluster 1A genes (SDHA, SDHB), 2 in Cluster 1B (VHL), and 2 in Cluster 2 (NF1). Consistent with existing literature, pathogenic germline variants—particularly SDHB and VHL—were identified in our cohort exclusively in patients younger than 30 years (ages 17, 20, and 25). Mutation-positive patients more frequently exhibited noradrenergic or non-secretory profiles (p = 0.01). Among the three non-secretory tumors in the cohort, two harbored genetic mutations (SDHA, NF1). Interestingly, both NF1-positive patients were normotensive—one (c.3496G > A) with a non-secretory tumor and the other (c.2329T > A) presenting at an unusually late age (63 years)—a strikingly atypical spectrum that underscores the phenotypic variability of NF1-associated PPGL. Bilateral disease was observed exclusively in VHL carriers (p = 0.03). Importantly, we identified a rare VHL c.369delG frameshift variant, not previously reported in association with PPGLs, in a patient with PPGL. No significant difference was observed between SDHB loss (p = 0.1) and proliferative indices (mitotic count, Ki-67) (p = 0.07, p = 0.6) between the two groups. During a median follow-up of 24 months (IQR: 18–36), one SDHB-positive patient had a recurrence, while no distant metastases were detected in the remaining mutation carriers. Conclusions: These findings support characteristic clinical patterns among mutation-positive PPGL and underscore the importance of systematic germline testing in all cases—irrespective of age, family history, or biochemical profile—to guide individualized management and enable cascade screening. The identification of a rare VHL c.369delG variant, previously unreported in association with PPGL, within a characteristic VHL-related clinical phenotype highlights the importance of this association. Similarly, atypical NF1 cases emphasize phenotypic variability and reinforce the importance of germline testing even in clinically silent presentations. Full article

Background/Objectives: Modifiable lifestyle factors, particularly diet, are important for preventing type 2 diabetes (T2D); however, the evidence regarding this from prospective studies is limited in the Asian population. We therefore evaluated whether a diet-inclusive healthy lifestyle score (HLS) predicts incident T2D in a community-based cohort. Methods: We analyzed 7185 T2D-free adults from the KoGES Ansan–Ansung cohort, constructing the HLS (range: 0–5) based on five lifestyle factors: non-smoking, ≥30 min/day of moderate-to-vigorous physical activity, low-risk alcohol consumption (≤40 g/day for men; ≤20 g/day for women), BMI of 18.5–24.9 kg/m², and a healthy diet, defined as a healthy plant-based diet index within the top 40th percentile. Cox proportional hazards regression models were employed to examine the association between HLS and incident T2D risk. Results: During a median follow-up of 17.5 years, 1223 cases of T2D were identified. Compared to individuals with a score of 0 or 1, those with a score of 5 had a 56% lower risk of T2D after adjustment for potential confounders (HR: 0.44, 95% CI: 0.32–0.62), and these associations remained consistent across subgroups stratified by age, sex, family history of T2D, hypertension, and residential area. However, the association was stronger among non-users of anti-diabetic medication than among users. Conclusions: Adherence to a healthier lifestyle, as indicated by a higher HLS, was significantly associated with a reduced risk of developing T2D among Korean adults. These findings underscore the importance of promoting integrated healthy lifestyle behaviors to prevent T2D. Full article

This study examines how parental legal status operates as a fundamental social determinant of health and educational equity, focusing on long-term outcomes among U.S.-born and foreign-born children of immigrants. We hypothesized that intergenerational stress and institutional exclusion associated with undocumented status would lead to lower educational attainment and poorer health. Using data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), a nationally representative cohort, participants were classified by inferred parental legal status: native-born, documented immigrant, and undocumented immigrant. Outcomes included high school graduation, college enrollment, depression scores, and chronic health conditions. Children of undocumented parents exhibited the most adverse outcomes—lower graduation (63.8%) and college enrollment rates (39.9%), higher depression, and greater chronic illness. In models controlling for socioeconomic factors, parental undocumented status independently predicted reduced odds of college enrollment (OR = 0.61, p < 0.001) and increased odds of reporting fair/poor health (OR = 2.10, p < 0.001). Findings highlight legal precarity as a potent driver of intergenerational disadvantage and underscore the need for policies addressing the barriers faced by children in undocumented families to promote health and educational equity. Full article

Background/Objectives: Blood renin and electrolyte levels are associated with blood pressure and hypertension. While sex-specific effects of such factors have been investigated, exact comparisons of the factors between the sexes have been scarce. Methods: Using cohort data from the Korean Genome and Environmental Study (KoGES), the study population that did not receive any interventions for blood pressure was determined. Blood levels of renin and electrolytes, including sodium, potassium, chloride, and calcium, were used to test their relationship with hypertension and blood pressure. Confounding variables, including age, body mass index (BMI), waist-to-hip ratio, family history of hypertension, alcohol consumption, smoking, blood urea nitrogen, creatinine, protein, and albumin levels, were used for adjustment in the multiple regression analysis. Results: In the single-variable analysis, sodium levels were significantly higher in the female population, and showed strong associations in the multiple regression analysis. Blood potassium levels showed no significant sex-specific differences. Among these factors, renin showed the greatest significance in both the total population and sex-specific groups. Moreover, in the development of hypertension, the effect size of renin was significantly different between sexes. Additionally, BMI tended to show stronger associations in females. Conclusions: This study identified sex-specific differential effects of renin and other electrolytes that are important in the pathophysiology of blood pressure. These findings provide clues for the more precise management of hypertension. Full article

Introduction: Nocturnal enuresis is defined as involuntary urination during sleep in children, particularly those aged 5 years or older. Primary monosymptomatic nocturnal enuresis (PMNE) involves nighttime wetting without daytime symptoms, and although factors like reduced bladder capacity, nocturnal polyuria, and impaired arousal contribute, predictors of long-term relapse remain uncertain. Methods: This retrospective cohort study included 227 children aged ≥5 years with strictly defined PMNE who achieved complete remission following a standardized 3-month treatment protocol (alarm therapy, desmopressin, or desmopressin plus oxybutynin). All children underwent ICCS-based assessment, including physical examination, urinalysis, ultrasonography, UFM, a 48 h frequency/volume (F/V) diary, and post-void residual measurement. One year after treatment discontinuation, patients were reassessed using a 14-day wet-night diary. Predictors of relapse were analyzed using comparative statistics. Result: At 1-year follow-up, 48.5% of children experienced relapse. Age, sex, treatment modality, family history, and baseline wet-night frequency were not associated with relapse (p > 0.05). Diary-based FBC was significantly higher than UFM-based capacity (p < 0.001). Reduced diary-based mean FBC/EBC ratios were significantly more common among relapsing children (p < 0.001), whereas UFM-derived ratios showed no significant difference (p = 0.052). ROC analysis demonstrated moderate discriminatory performance for diary-based FBC/EBC (AUC 0.671). A ratio > 79% predicted sustained remission with 83.6% specificity and a positive predictive value of 73.5%. Conclusions: Diary-derived bladder capacity is the strongest predictor of long-term relapse in PMNE and outperforms UFM-based assessment. A mean FBC/EBC ratio > 79% provides a clinically useful threshold for identifying children at low risk of recurrence. Those with reduced diary-based capacity may benefit from closer follow-up or extended maintenance therapy. Full article

Apolipoprotein B (APOB) is a key structural component of atherogenic lipoproteins and one of the principal genes implicated in familial hypercholesterolemia (FH). However, APOB genetic variation remains poorly characterized in Latin American and admixed populations. In this study, we performed a descriptive analysis of APOB variants in 60 Ecuadorian mestizo patients with inherited cardiac conditions using next-generation sequencing (NGS) and genetic ancestry inference. A total of 227 APOB variants were identified, the majority of which were classified as benign (n = 220) or likely benign (n = 3) according to ACMG criteria, while three variants were classified as variants of uncertain significance (VUS). The most frequently observed variants included rs1042034, rs679899, rs676210, and rs1367117. Comparative allele-frequency analyses using ALFA and PAGE Latin American reference datasets demonstrated that the APOB variant frequencies observed in the cohort were comparable to those reported in other Latin American populations, reflecting the admixed genetic background of Ecuadorian mestizos, predominantly of Native American and European ancestry. No pathogenic APOB variants were detected. Although lipid measurements were not available and genotype–phenotype associations could not be assessed, this study provides the first comprehensive overview of APOB variation in Ecuadorian mestizo individuals. These findings expand population-specific genomic data for an underrepresented group and underscore the importance of regional reference datasets for accurate variant interpretation in admixed populations. Full article