Search Results (25,503)

Background/Objectives: The nutrition transition in low- and middle-income countries has produced a double burden of malnutrition (coexistence of excess weight, undernutrition, and micronutrient deficiencies), with scarce evidence in schoolchildren from vulnerable peri-urban areas of Paraguay. The objective was to characterize, in a multidimensional way, the nutritional status of children and adolescents from Limpio and to explore its associations with anemia and clinical, dietary, and environmental variables, in particular, reported intestinal parasitosis. Methods: Cross-sectional observational study in 90 participants aged 6 to 16 years recruited by convenience at six community settings. Anthropometry, body composition, capillary hemoglobin, dietary patterns, and environment were assessed. Weight status was classified using the WHO 2007 references (z-scores), anemia was described using WHO thresholds, and central obesity was assessed using a waist-to-height ratio > 0.5. Non-parametric tests, Fisher’s exact test, Spearman correlations, and multivariable logistic regression were used. Results: Overweight or obesity affected 39.3% (obesity, 16.7%) and central obesity 22.4%, with no cases of thinness, coexisting with anemia (27.0%), stunting (8.2%), and reported intestinal parasitosis (24.1%). Anemia was more frequent in children with reported intestinal parasitosis (45% versus 20%; adjusted OR 5.44; 95% CI 1.44–20.51). Height-for-age was inversely associated with the number of siblings (ρ = −0.25). Conclusions: This population showed a double burden of malnutrition. The association between reported, non-laboratory-confirmed intestinal parasitosis and capillary-hemoglobin-defined anemia was exploratory and non-causal, given the cross-sectional design. Together with the high burden of anemia, these findings raise the hypothesis of a possible triple burden of malnutrition, which would require confirmation through stool parasitological testing and biomarkers of iron status, inflammation, and other micronutrients. These findings are compatible with integrated community strategies addressing dietary quality, sanitation, and access to safe water; decisions on deworming and micronutrient supplementation should be guided by local parasitological surveillance and biomarker-based assessment rather than by these data alone. Because the study used a convenience sample from a single peri-urban community during one fieldwork period, the findings should not be generalized beyond similar vulnerable settings without further confirmation. Full article

Hypogonadism is increasingly recognized as an independent cardiovascular risk factor, with testosterone deficiency associated with endothelial dysfunction, increased thrombotic risk, and adverse cardiovascular outcomes. Circulating biomarkers provide valuable insights into the vascular health status of hypogonadal men and the cardiovascular effects of testosterone replacement therapy (TRT). This comprehensive review examines the molecular basis of testosterone action on the cardiovascular system and synthesizes evidence on circulating cardiovascular biomarkers in hypogonadism, including endothelial progenitor cells (EPCs), endothelial microparticles (EMPs), platelet markers, endothelial activators, adhesion molecules, and inflammatory/oxidative stress markers. We also compare the cardiovascular safety profiles of transdermal versus intramuscular testosterone formulations. Hypogonadal men exhibit reduced circulating EPCs, elevated EMPs, increased platelet reactivity, higher levels of endothelial activators (ICAM-1, VCAM-1, E-selectin, von Willebrand factor, endothelin-1, ADMA), and increased inflammatory markers (hsCRP, IL-6, TNF-α). TRT improves most of these biomarkers through androgen receptor (AR)-dependent and AR-independent mechanisms involving PI3K/Akt/eNOS signaling, VEGF upregulation, CXCL12/CXCR4 axis modulation, and NF-κB pathway suppression. Current evidence suggests that transdermal testosterone formulations may offer advantages regarding hematological safety and more stable testosterone exposure; however, definitive evidence demonstrating superior cardiovascular outcomes compared with intramuscular formulations remains limited. Circulating cardiovascular biomarkers are significantly altered in hypogonadism and improve with TRT. Available data suggest that transdermal testosterone formulations may offer a more favorable cardiovascular safety profile than intramuscular preparations, particularly with respect to erythrocytosis and pharmacokinetic stability, although head-to-head randomized trials with hard cardiovascular endpoints are still needed. Understanding the molecular mechanisms underlying these changes is essential for optimizing TRT in hypogonadal men with cardiovascular risk factors. The cardiovascular safety advantage of transdermal formulations is currently supported primarily by pharmacokinetic and hematological evidence; direct comparative evidence from randomized trials with hard cardiovascular endpoints remains unavailable. Full article

Background/Objectives: Fortified eggs have been proposed as food-based vehicles for delivering micronutrients and other bioactive compounds. However, human intervention evidence remains fragmented across nutrient targets, populations, intervention designs, and outcome domains. This review mapped human intervention studies and summarized the reported nutritional and health-related outcomes associated with fortified egg consumption. Methods: PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang Data, and SinoMed were searched for studies published in English or Chinese from 1 January 2005 to 1 June 2025. Eligible studies were human intervention studies evaluating fortified, enriched, or bio-enhanced eggs and reporting at least one nutritional or health-related outcome. Owing to substantial heterogeneity in nutrient type, intervention design, comparator, duration, and outcome assessment, findings were synthesized narratively. Results: Thirty-seven human intervention studies met the eligibility criteria. Most evaluated eggs enriched with n-3 polyunsaturated fatty acids, followed by carotenoid-enriched eggs, whereas relatively few examined iodine or other fortified nutrients. Across studies, fortified egg consumption was generally associated with improvements in intake estimates and biomarkers of targeted nutrient status, including circulating fatty acids, serum carotenoids, and, in a limited number of studies, urinary iodine. Evidence for downstream health-related outcomes was more limited, inconsistent, and difficult to compare across nutrient categories and study populations. Conclusions: Fortified eggs may serve as useful food-based vehicles for improving the delivery of selected nutrients and short-term nutrient-status biomarkers. However, the evidence base remains heterogeneous and nutrient-specific, and it is still uncertain whether these changes translate into consistent, clinically meaningful health benefits. Larger, longer-term, and more rigorously reported trials, particularly in populations at nutritional risk, are needed. Full article

C-type lectin receptors (CLRs) play central roles in sensing fungal pathogens and coordinating Syk-CARD9-dependent inflammatory responses. While Dectin-3 contributes to antifungal immunity against several clinically relevant fungi, its role in host defense against Paracoccidioides brasiliensis remains unknown. Here, we investigated the impact of Dectin-3 deficiency using Clec4d⁻/⁻ mice and primary phagocytes during experimental Paracoccidioidomycosis. Dectin-3-deficient macrophages and dendritic cells displayed unaltered cytokine production, phagocytic capacity, fungicidal activity, and maturation following P. brasiliensis challenge. Consistently, the absence of Dectin-3 did not impact survival or pulmonary fungal burden during long-term systemic infection. These findings are consistent with functional redundancy among CLRs, potentially involving Dectin-1, Dectin-2, or other Syk-coupled receptors rendering Dectin 3 dispensable for immunity to systemic experimental P. brasiliensis infection. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) remains a highly aggressive malignancy with poor clinical outcomes. Although poly(ADP-ribose) polymerase (PARP) inhibitors have shown promising activity in tumors with homologous recombination deficiency, their efficacy in BRCA wild-type HNSCC remains limited. Reactive oxygen species (ROS)-induced DNA damage may increase cellular dependence on DNA repair pathways and thereby enhance sensitivity to PARP inhibition. This study investigated whether ROS-mediated DNA damage could sensitize BRCA wild-type HNSCC cells to the PARP inhibitor olaparib. Methods: BRCA wild-type HSC-3 and SCC-25 HNSCC cell lines were exposed to H₂O₂ to induce oxidative stress. Intracellular ROS levels were quantified using DCFDA assays, DNA double-strand breaks were evaluated by γ-H2AX ELISA, PARP activity was assessed by ELISA, and cell viability was determined using MTT assays. Expression levels of DNA repair genes (PARP1, PARP2, BRCA1, BRCA2, RAD51, and MLH1), checkpoint kinases (ATM, ATR, and CHK1), the homologous recombination regulator FANCD2, and redox defense genes (NQO1, GPX4, and SLC7A11) were analyzed by qRT-PCR. Therapeutic selectivity was assessed using HGF-1 normal human gingival fibroblasts as a normal cell control. Apoptosis was measured through caspase-3/7 activity assays, and drug interactions were evaluated using the Chou–Talalay method. Results: H₂O₂ treatment increased intracellular ROS levels in both cell lines, accompanied by significant induction of DNA damage as demonstrated by elevated γ-H2AX levels. ROS induction markedly enhanced olaparib sensitivity, significantly reducing IC₅₀ values in both HSC-3 and SCC-25 cells. Combined H₂O₂ and olaparib treatment produced strong synergistic cytotoxicity, suppressed DNA repair, checkpoint kinase, and redox defense gene expression, and increased caspase-3/7 activity compared with control cells. Importantly, the combination demonstrated selective cytotoxicity toward cancer cells, with normal HGF-1 cells retaining significantly higher viability. Conclusions: ROS-induced DNA damage significantly enhances the anti-tumor activity of olaparib in BRCA wild-type HNSCC cells through a functional synthetic lethal-like interaction involving the simultaneous collapse of DNA repair capacity, checkpoint activation, and oxidative stress buffering, culminating in apoptosis induction. These findings support the rationale for combining ROS-generating therapies with PARP inhibitors in HNSCC treatment. Full article

Metabolic dysfunction-associated steatohepatitis (MASH; formerly non-alcoholic steatohepatitis, NASH) is characterized by oxidative stress, inflammatory activation, hepatocellular injury, and progressive liver dysfunction. However, the global transcriptomic landscape underlying stress-induced hepatic injury remains incompletely understood. In this study, we employed a methionine–choline-deficient (MCD) diet-induced murine model to characterize the phenotypic and transcriptomic alterations associated with liver injury. Male C57BL/6J mice were fed either a control or MCD diet, and hepatotoxicity was assessed by survival analysis, body and liver weight measurements, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, histopathological examination, RNA sequencing, quantitative real-time PCR (qRT-PCR), and tumor necrosis factor-alpha (TNF-α) enzyme-linked immunosorbent assay (ELISA). MCD feeding markedly reduced survival and body weight while inducing hepatomegaly and significant elevations in serum ALT and AST, indicating severe hepatocellular injury. Histopathological analysis demonstrated hepatic steatosis, hepatocellular ballooning, and lobular inflammation without histological evidence of fibrosis. Transcriptomic profiling revealed extensive gene expression remodeling, characterized by activation of inflammatory pathways, enrichment of MAPK-related signaling, dysregulation of lipid metabolism, suppression of antioxidant defense systems, impairment of cytochrome P450-mediated detoxification, and upregulation of apoptosis-associated genes. qRT-PCR further validated the differential expression of representative genes involved in inflammatory signaling (Tlr4, Nfkb1, Nlrp3, and Casp1), MAPK signaling (Fos), xenobiotic metabolism (Cyp4f18), lipid metabolism (Apoa4 and Lpl), extracellular matrix remodeling (Mmp12), and oxidative stress responses (Sod1 and Gstp1). In addition, elevated serum TNF-α levels provided protein-level evidence supporting activation of the TLR4/NF-κB/TNF-α/NLRP3 inflammatory axis. Although fibrosis-associated transcriptional responses were detected, the absence of histological fibrosis suggests transcriptional priming of fibrogenic pathways rather than established fibrogenesis. Collectively, these findings provide a transcriptomic framework linking oxidative stress, impaired detoxification, inflammatory activation, and stress-responsive signaling to MCD-induced hepatic injury. The MCD model provides a valuable experimental platform for characterizing hepatic stress-response transcriptomes and for generating hypotheses that can subsequently be evaluated in environmentally relevant toxicological models. Nevertheless, caution should be exercised when extrapolating these findings to obesity-associated human MASLD, as the MCD model lacks key metabolic features of the human disease, including obesity and insulin resistance. Therefore, the present findings should be interpreted primarily as transcriptomic signatures of stress-induced hepatic injury rather than as a direct representation of the pathophysiological processes underlying human obesity-associated MASLD. Full article

Heavy metal (HM) contamination near mining operations in Kazakhstan poses a serious threat to the environment. However, data on the state of chernozem soils in this region is limited. This study assessed the bioaccumulation of HMs and translocation within the soil–sunflower (Helianthus annuus L.) system in a southern Calcic Chernozem in the Kostanay region (Northern Kazakhstan), which is located 50 km from the nearest mining facility. The content of seven HMs (Cd, Co, Cr, Cu, Ni, Pb, and Zn) and arsenic (As), as well as five macroelements (K, Ca, S, Mg, and P), was determined in 18 soil samples from the complete soil pedon (0–150 cm) and in eight anatomical parts of six sunflower plants at physiological maturity. Most metals exhibited a deficiency relative to upper continental crustal Clarke values (Clarke of Concentration (CC) < 1 for Cr, Cu, Ni, Pb, and Zn), with a moderate lithogenic anomaly for Cd (CC = 1.65–3.57) and a localized Co anomaly in the Bk horizon (56.26 mg kg⁻¹), indicating no pronounced HM contamination at the investigated agricultural site. Metal distribution exhibited strong organ specificity in sunflower plants. Cd, Cu, and Zn accumulated preferentially in the leaves, whereas Ni and Co were more concentrated in the seeds and stems, respectively. Only cadmium exceeded the threshold values for both BCF > 1 (1.01) and TF > 1 (1.47), confirming the status of sunflower as a cadmium accumulator. These results provide a preliminary reference dataset of the organ-specific distribution of heavy metals in H. annuus L. plants, which can serve as a local baseline for sunflower growth in uncontaminated southern Chernozems. This information can contribute to future environmental monitoring purposes in the region, acting as an exploratory benchmark. Full article

Cytoreductive surgery remains one of the key treatment modalities in advanced ovarian cancer. Complete cytoreduction is the main surgical goal. PARP inhibitors are currently established mainly as maintenance therapy after response to platinum-based chemotherapy, particularly in patients with BRCA-mutated or homologous recombination-deficient tumors. Their use before cytoreductive surgery remains investigational. This review evaluates preoperative PARP inhibition from a surgical perspective. This narrative review summarizes current evidence, ongoing clinical trials, and perioperative considerations related to preoperative or neoadjuvant PARP inhibitor strategies in advanced ovarian cancer. Particular attention was given to the review of current clinical trials’ strategies, resectability, complete cytoreduction, patient selection, perioperative safety, treatment timing, and surgery-specific endpoints. Current studies explore several preoperative approaches, including short window-of-opportunity treatment before primary debulking surgery, PARP inhibitor monotherapy as potential conversion therapy in homologous recombination-deficient disease, PARP inhibitor-based strategies before interval debulking surgery, combination regimens with immunotherapy or antiangiogenic therapy, and preoperative PARP inhibitor use before secondary cytoreduction in recurrent disease. These studies suggest that preoperative PARP inhibition may provide biological and surgical insights, but available evidence remains preliminary. Key concerns include hematologic toxicity, surgical postponement, perioperative complications, wound healing, postoperative recovery, and the risk of delaying standard chemotherapy or surgery. Preoperative PARP inhibitor therapy is theoretically promising but an unproven strategy in ovarian cancer. Its future value will depend on prospective trials showing that it can safely improve resectability and complete cytoreduction without compromising treatment timing. Future studies should include surgery-specific endpoints in addition to conventional oncologic outcomes. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease (CLD) globally and is closely linked to metabolic risk factors and systemic inflammation. Emerging evidence suggests that vitamin D deficiency may influence MASLD severity and outcomes, though limited real-world data often assess long-term clinical outcomes in MASLD patients stratified by vitamin D status. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (2006–2025). Adult patients with MASLD were stratified into two cohorts based on serum 25-hydroxyvitamin D levels: normal (≥30 ng/mL) and deficient (<20 ng/mL). Patients with other CLD, malignancy, decompensated cirrhosis, and relevant confounding conditions were excluded. Primary outcomes included all-cause mortality, hospital readmissions, and ICU admissions at 1-year and 5-year follow-up. Results: After propensity score matching, 6959 patients were included in each cohort. Compared with patients with normal vitamin D levels, those with vitamin D deficiency had significantly higher rates of hospital readmissions, ICU admissions, and all-cause mortality at both 1-year and 5-year follow-up. A 1 year, readmissions occurred in 10% vs. 6%, ICU admissions 2.6% vs. 1.2%, and mortality 1.5% vs. 0.5% of patients (p = 0.01). Similar findings were observed at 5 years, with higher rates of readmissions 15% vs. 10%, ICU admissions 4.4% vs. 2.4% and mortality 3.2% vs. 1.3% in the vitamin D-deficient cohort (p = 0.01). Conclusions: Vitamin D deficiency was associated with significantly increased mortality, hospital readmissions, and ICU admissions among patients with MASLD. Our findings suggest that vitamin D status may represent a valuable prognostic indicator in this population. Although the observational nature of this study precluded establishing causality, our results support the consideration of routine assessment of vitamin D levels in patients with MASLD. Further prospective and mechanistic studies are needed to determine whether vitamin D supplementation can improve outcomes in this population. Full article

Water-soluble blue microbial pigments with antioxidant activity remain rare, and their host-level protective mechanisms are poorly understood. Here, we identified the genetic basis of blue pigment biosynthesis in the glacier-derived strain Arthrobacter antioxidans QL17. Heavy-ion mutagenesis yielded a hyperpigmented mutant (M157) and a pigment-deficient mutant (M186), and pigment yield was positively associated with hydrogen peroxide (H₂O₂) tolerance. Genome mining identified MWM45_RS16760 as the sole core biosynthetic gene in a candidate nonribosomal peptide synthetase (NRPS)-like cluster. The encoded protein displayed an adenylation–peptidyl carrier protein–thioesterase (A-PCP-TE) architecture with a predicted L-glutamine-specific A domain, and its transcript abundance paralleled pigment production across the three strains. Phylogenetic analysis placed MWM45_RS16760 in a distinct actinomycete-associated indigoidine-like lineage separated from the characterized BpsA and IndC branches. Heterologous expression in Escherichia coli reconstructed a blue-pigment-producing phenotype, increased H₂O₂ tolerance, and was accompanied by enhanced extracellular DPPH and ABTS radical-scavenging activities in the culture supernatant. Comparative transcriptomics further revealed coordinated activation of oxidative-stress and proteostasis responses alongside repression of tryptophan biosynthesis and flagellar assembly. These findings identify MWM45_RS16760 as a candidate indigoidine-like NRPS associated with blue pigment biosynthesis and oxidative-stress resistance, with heterologous expression linked to enhanced radical scavenging and coordinated transcriptional reprogramming, expanding the phylogenetic and functional diversity of indigoidine-like systems. Full article

Lycopene is a highly significant carotenoid in daily life, exhibiting potent antioxidant properties and recognized as one of the most powerful natural antioxidants identified in plants to date. Its functionality originates from electronic and vibrational states that exhibit a high sensitivity to environmental perturbations. Nevertheless, exclusively experimental methodologies face challenges in delivering a comprehensive molecular-level comprehension of the influence exerted by particular environmental factors on the vibronic characteristics. This deficiency in understanding hinders the accurate prediction of its behavior and functional performance within complex systems. The first principle computational investigation enables a precise elucidation of the coupling mechanisms between electronic excitations and vibrational modes under diverse solvation and interaction environments. The results indicate that the local environment significantly influences the charge distribution and orbital energies of lycopene, altering its vibrational and electronic state properties. This provides a fundamental theoretical framework for predicting their photophysical behavior and biological functions within complex matrices. Full article

Dental fluorosis (DF) is a common endemic disease that damages dental enamel. Traditionally, DF has been attributed to environmental fluoride overload. Accumulating evidence has demonstrated that genetic factors also modulate individual susceptibility. No dedicated fluoride ion channels have been identified in mammalian cells; fluoride uptake is believed to occur mainly through passive diffusion of HF and nonspecific anion pathways, including chloride channels. Different types of chloride channels are expressed in dental tissues, such as CFTR and voltage-gated chloride channels (ClCs), but it remains unknown whether these channels transport fluoride and whether their variants influence DF risk. This study combined human population-based investigations, mouse and zebrafish models, and in vitro experiments to confirm the significant genetic association of CFTR and CLCN3 variants with DF. A total of 889 DF cases and 834 matched controls were recruited from the same fluoride-contaminated region. Tag SNP screening of CFTR and eight ClC chloride channel genes (CLCNs) revealed that rs213950 in CFTR and three SNPs in CLCN3 were significantly associated with DF. CFTR and ClC-3 showed different fluoride tolerances. rs213950 in CFTR affected the efficiency of fluoride ion transport in Xenopus oocytes. ClC-3 enabled yeast cells to resist fluoride toxicity, whereas clcn3 deficiency disrupted tooth and craniofacial development in zebrafish. Fluoride exposure altered nucleoprotein binding to the rs10520161 region and changed the mRNA levels of various ClC-3 transcripts. These transcripts displayed different subcellular locations and fluoride conductances and acted synergistically to confer fluoride resistance. Together, these findings raise the possibility that variants in CFTR and CLCN3 may act synergistically to influence DF susceptibility. This potential interplay highlights DF as a complex trait involving dysregulated fluoride handling and underscores the multifactorial, gene-directed regulation of fluoride transport. Full article

Background: The incidence of early-onset colorectal cancer (EOCRC) is rising, yet the relative contribution of metabolic, inflammatory, and laboratory abnormalities remains incompletely defined. Objectives: We compared these associations between EOCRC and late-onset colorectal cancer (LOCRC) while addressing the possibility that some laboratory abnormalities may reflect occult cancer rather than antecedent risk. Methods: We conducted a matched case–control study using the TriNetX US Network. Adults diagnosed with CRC between 2010 and 2023 were identified as EOCRC (18–49 years) or LOCRC (50–75 years). Patients with prior malignancy, inflammatory bowel disease, hereditary or familial CRC risk, or prior colectomy were excluded. Three separate analyses were performed. First, a direct EOCRC-versus-LOCRC comparison evaluated gastrointestinal symptoms during the 6 months preceding diagnosis. Second, EOCRC and LOCRC were each compared with their respective matched cancer-free controls to assess clinical, metabolic, and laboratory features during the 24 months preceding diagnosis. When multiple laboratory values were available, the most recent value preceding the index date was used. Conditional logistic regression estimated adjusted odds ratios with 95% confidence intervals, with Bonferroni correction applied for multiple comparisons. Results: The direct matched EOCRC-versus-LOCRC comparison included 7752 patients with CRC, comprising 2584 with EOCRC and 5168 with LOCRC. EOCRC more frequently presented with rectal bleeding, abdominal pain, diarrhea, iron-deficiency anemia, and weight loss. Rectal tumors were more common in EOCRC, whereas proximal tumors were more common in LOCRC. In separate control-based analyses, 3217 patients with EOCRC and 12,112 patients with LOCRC were compared with 6434 and 24,336 matched cancer-free controls, respectively. The strongest independent features associated with EOCRC were severe obesity (aOR 2.61), microcytosis (aOR 2.29), low ferritin (aOR 2.11), and elevated C-reactive protein (aOR 1.87). Similar but generally attenuated associations were observed in LOCRC. In adjusted EOCRC-versus-LOCRC analyses, obesity (aOR 1.38), metabolic syndrome (aOR 1.41), and MASH (aOR 1.22) remained more closely associated with EOCRC. Conclusions: EOCRC is associated with a distinct clinical–metabolic phenotype, with more pronounced metabolic, inflammatory, and hematologic abnormalities than LOCRC. These findings should be interpreted as hypothesis-generating prediagnostic associations, not as validated predictors or causal risk factors. Full article

CdS and Cd-deficient CdS (D-CdS) were prepared using a simple hydrothermal method. Pristine CdS exhibited slow electron transfer and limited active sites in periodate (PI) activation, while Cd vacancy defect engineering proposed in this work effectively overcame these drawbacks. The optimal Cd-deficient D-CdS8 could effectively activate PI and exhibit excellent degradation performance toward tetracycline (TC). Within 90 min, the D-CdS8/PI system could achieve 92.3% removal of 10 mg L⁻¹ TC. This study systematically explores the influences of different factors and coexisting substances on TC degradation. Radical quenching experiments revealed that IO₃· and ·OH were the dominant reactive species for TC degradation in D-CdS8/PI system. Electrochemical characterization indicated that the introduction of Cd vacancies made D-CdS8 possess higher electron transfer efficiency. The D-CdS8/PI system achieved enhanced PI activation and improved TC degradation, with reaction rates 2.15 times superior to the CdS/PI system. Furthermore, degradation pathways and toxicological analysis of intermediates for TC degradation were also conducted. This study provided a simple and feasible strategy for developing efficient defective catalysts for the remediation of antibiotic-contaminated water. Full article

Background/Objectives: Childhood and adolescence are critical periods for bone mineral accrual and future skeletal reserve. Milk intake, sun exposure and caffeinated energy drink consumption are familiar lifestyle concepts, but they differ substantially in biological proximity and evidential strength. This structured narrative review critically evaluates these exposures in relation to peak bone mass accrual in youth. Methods: PubMed/MEDLINE, Scopus, Web of Science, the Cochrane Library and Google Scholar were searched from database inception to 23 June 2026. Search terms combined pediatric population terms with bone outcomes and exposure terms related to milk/dairy, calcium, vitamin D, sun exposure, physical activity, sleep, caffeine and energy drinks. A literature collection flowchart and a GRADE-informed evidence appraisal table are provided to improve transparency and clinical interpretability. Results: Evidence is strongest for adequate calcium intake, calcium-rich foods and weight-bearing physical activity as modifiable contributors to skeletal accrual. Vitamin D is essential for mineral homeostasis, but supplementation effects on bone density in otherwise healthy children are context-dependent and appear most relevant for deficiency prevention or treatment. Milk intake is best interpreted as a practical marker of calcium-rich dietary patterns rather than as the only route to calcium adequacy. Sun exposure is an indirect determinant of vitamin D status and is modified by season, latitude, skin pigmentation, clothing, sunscreen, adiposity and outdoor behavior. Direct evidence linking caffeinated energy drinks to impaired pediatric bone accrual is very limited. The relevance of caffeinated energy drink intake is better framed as indirect and hypothesis-generating, through possible displacement of calcium-rich beverages, sleep disruption and clustering with poorer lifestyle patterns. Conclusions: A prevention framework for pediatric bone health should emphasize calcium adequacy, avoidance of vitamin D deficiency, mechanical loading and correct pediatric DXA interpretation using Z-scores. Energy drinks can be included as a lifestyle concern, but conclusions should remain cautious because direct skeletal evidence is limited. Full article