Search Results (901)

Bronchopulmonary dysplasia (BPD) is a chronic lung condition in preterm infants characterized by impaired alveolar development, disrupted vascular growth, and persistent inflammation. These alterations, which often arise from early exposure to mechanical ventilation, oxygen toxicity, and infection, can lead to long-term structural and functional deficits in the developing lung. In adulthood, chronic obstructive pulmonary disease (COPD) represents a major cause of morbidity and mortality and is defined by progressive airflow obstruction, reduced respiratory capacity, and chronic inflammatory responses. Although traditionally considered a disease of adult smokers, growing evidence suggests that early-life respiratory insults play a key role in shaping long-term lung health. Recent studies reveal a biologically plausible link between BPD and later COPD, indicating that premature birth, impaired lung growth, and early inflammatory injury may predispose individuals to earlier or more severe COPD development. This review explores the shared molecular pathways connecting these conditions, focusing on overlapping inflammatory biomarkers such as IL1B, IL6, IL8, TNF, TGFB, and VEGF, which collectively reflect persistent dysregulation of immune and repair mechanisms. Additionally, common genetic variants, including SERPINA1 and HHIP, may contribute to susceptibility across the lifespan. Emerging biomarkers—such as PRMT7, cathelicidin/LL-37, CRISPLD2, and GDF15—offer further insight into disease progression. Identifying these shared markers may ultimately improve early detection and help clinicians pinpoint infants with BPD who face an elevated risk of developing COPD later in life. Full article

The first 1000 days of life, starting from conception to a child’s second birthday, constitute a pivotal period for fetal lung and pulmonary vascular development. Maternal nutrition during this period plays an important role in fetal growth, immune programming and organ development, including that of the pulmonary system. This narrative review consolidates evidence linking maternal nutrition and early-life nutrient intake during this period with the development of pulmonary hypertension in the newborn. We examine the influence of both nutrient deficiencies and excesses on fetal lung and vascular development. We performed a structured search of PubMed and Embase (conducted from February 2025 to March 2025) and screened reference lists. Twenty-eight peer-reviewed studies were included, comprising human clinical and observational evidence and studies on animal models. The findings suggest that imbalances in maternal diet can disrupt placental function, induce inflammation, and trigger epigenetic alterations, all contributing to pulmonary vascular dysfunction and increased pulmonary hypertension susceptibility in neonates. Notably, maternal undernutrition and thiamine deficiency during lactation have been directly linked to pulmonary hypertension in infants. Conversely, high-fat diets and excessive polyphenol intake have been associated with adverse fetal cardiovascular remodeling. While current evidence is primarily derived from animal models and observational studies, it highlights the urgent need for targeted nutritional strategies and clinical trials during pregnancy. Although human causality is unproven for most exposures, studying maternal nutrition in the first 1000 days could offer a cost-effective method for reducing the burden of pediatric pulmonary hypertension and its long-term consequences and for prospective trials aimed at preventing early-life pulmonary vascular disease. Full article

Background: Subclinical respiratory impairment among non-smokers in regions with haze-affected regions is still under-recognized, particularly in low- and middle-income countries (LMICs). This study assessed the prevalence of subclinical respiratory impairment among non-smoking adults and examined its determinants and associations with health-related quality of life (HRQoL) in Chiang Mai, Thailand. Methods: In this cross-sectional study, 244 non-smoking adults (18–65 years) from three rural districts underwent standardized spirometry and completed the Thai WHOQOL-BREF-26. Subclinical impairment was defined as an FEV₁/FVC < 0.70 or FVC < 80% predicted in the absence of symptoms. Demographic, occupational, and environmental information was obtained through structured questionnaires. Statistical analyses included non-parametric tests, univariate linear regression, and logistic regression. Results: A total of 37 participants (15.2%) had subclinical respiratory impairment. No demographic, occupational, or environmental factors such as sex, age, BMI category, agricultural work, marital status, and self-reported pollution exposure were found to be independently linked to impaired lung function. There was no correlation between spirometry indices and any WHOQOL-BREF domain. Elderly participants (>50 years) reported a higher level of physical and psychological HRQoL. Those with a higher Body Mass Index (BMI) were more likely to have a lower environmental quality of life. Farmers reported a better QoL, while women reported a lower QoL than men. Conclusions: Subclinical respiratory impairment occurs frequently in non-smoking rural adults exposed to haze pollution in Chiang Mai, and isn’t presently assessed by general HRQoL instruments. These findings support early spirometry screening for asymptomatic adults in polluted regions, as well as more stringent air cleanliness strategies to prevent the evolution towards overt respiratory pathology. Full article

Leptospirosis is an important zoonosis that can present as a self-limited influenza-like illness or progress to severe, including life-threatening multiorgan dysfunction. We report the epidemiology, clinical profile, and correlates of severity among adults hospitalized patients with leptospirosis diagnosed in central Romania over a period of 17 years. We conducted a retrospective, single-center cohort study of adults admitted between 1 January 2008 and 1 December 2025 with laboratory-confirmed leptospirosis. Confirmation was based on positive anti-Leptospira IgM serology, with repeat testing when the initial result was equivocal and confirmation with a microscopic agglutination test. We extracted demographic, exposure, clinical, laboratory, treatment, and outcome data from medical records. The modified Faine score was also calculated using admission data. Sixty-four patients were included in this analysis, of which 53 (82.8%) were male patients. Admissions peaked in 2023–2025 (34/64, 53.1%) and in the August–September months. Reported exposures were predominantly peri-domestic (46.9%), followed by rural/animal-related occupations (20.3%) and freshwater contact (17.2%). Severe disease occurred in 26/64 (40.6%), was more frequent in men (p = 0.021), and was more common pre-pandemic than during/after the pandemic (p < 0.001). Severe cases were associated with oliguria/anuria, hematuria, and jaundice, alongside higher urea/creatinine and bilirubin, lower hemoglobin and lymphocyte percentages, and a longer hospitalization period. One in-hospital death occurred (1.6%). Serogroup identification was available for 10 patients (15.6%) (pre-pandemic only). The mean modified Faine score was 27.5 ± 6.0. In this temperate-region cohort study, hospitalized leptospirosis showed a marked male predominance, a late-summer peak, and a substantial burden of severe disease. Early renal and hepatobiliary manifestations with concordant laboratory abnormalities may support timely risk stratification and escalation of care, while expanded molecular diagnostics and systematic typing are needed to clarify temporal trends and guide prevention. Full article

Background/Objectives: Hydroxyurea is currently the standard disease-modifying therapy for reducing sickle cell disease (SCD) complications; however, drug labels currently advise discontinuation of breastfeeding during hydroxyurea therapy due to limited human data on the risk of hydroxyurea exposure in breastfed neonates. Methods: A physiologically based pharmacokinetic (PBPK) model for hydroxyurea was built and verified with data from non-lactating adult patients with SCD. The model was then extended to predict hydroxyurea in nursing and in paediatric populations. Predictions were compared to the observed data. Results: The PBPK model predictions for hydroxyurea pharmacokinetics described the observed data in both adult and paediatric subjects with SCD. Observed concentration profiles were within the 5th–95th prediction intervals, and predicted PK parameters were within 2-fold of the observed values. The predicted milk-to-plasma ratio was 0.8. Neonatal exposure to hydroxyurea via breast milk as a percentage of maternal exposure increased from 0.6% at 1 day to 10% at the 4th week postpartum before declining to 5%, 3%, and 2% at 6, 9, and 12 months postpartum, respectively. Conclusions: About 56% of total milk hydroxyurea exposure is within the first 3 h of post-maternal dose. Disposal of this early milk would reduce the exposure of breastfed children. The reduction in exposure is especially pronounced around the first 1 month postpartum. Lactation PBPK models offer a physiological approach to assess real-life scenarios that are difficult to investigate in clinical studies and provide useful results for future clinical study design and clinical recommendations. This was exemplified with hydroxyurea in the current work. Full article

Background/Objectives: Intestinal colonization by Enterobacteriaceae, including extended-spectrum β-lactamase-producing (ESBL-E) and carbapenemase-producing (E-CPE) strains, is an early marker of multidrug-resistant infections in neonates, particularly those transferred from lower-complexity hospitals. This study aimed to identify factors associated with intestinal Enterobacteriaceae colonization upon admission to a level IV neonatal referral unit in Colombia, with a focus on prior antibiotic exposure. Methods: We conducted a retrospective case–control study, including all neonates transferred from peripheral hospitals and screened with rectal swabs at admission. Cases were neonates colonized with Enterobacteriaceae, and controls were non-colonized neonates admitted during the same period. Multivariable logistic regression models were used to evaluate three exposure dimensions: prior antibiotic use (yes/no), number of agents, and the WHO AWaRe classification. A secondary analysis was performed to assess the factors associated with ESBL-E and E-CPE colonization. Results: Among the 435 referred neonates, 87 (20.0%) were colonized, predominantly Klebsiella pneumoniae (53.6%) and Escherichia coli (19.5%). Prior antibiotic use (aOR 3.01; 95% CI 1.47–6.37), exposure to two agents (aOR 4.13; 95% CI 1.94–8.89) and use of AWaRe Access antibiotics (aOR 22.2; 95% CI 5.83–101) were strongly associated with colonization. Longer hospitalization and central catheter use were also associated with greater colonization odds, whereas total parenteral nutrition showed a protective association. In the sub-analysis, Access, Watch, and Reserve antibiotics were independently associated with ESBL-E and E-CPE colonization. Conclusions: Among transferred neonates, prior antibiotic exposure, particularly AWaRe-classified agents, showed the strongest association with intestinal colonization by Enterobacteriaceae, including ESBL-E/CPE phenotypes. Strengthening antimicrobial stewardship in referral facilities and implementing risk-based screening at admission may help reduce colonization and limit the spread of resistance. Full article

There is increasing evidence that exposure to environmental toxicants may impact fertility, especially during critical windows of reproductive axis development. Hypothalamic gonadotropin-releasing hormone (GnRH) neurons, essential for puberty onset and fertility, originate from the olfactory placode and migrate toward the hypothalamus during development, making them particularly vulnerable to environmental insults. Cadmium (Cd), a widespread heavy metal, is well known for its gonadotoxicity, but its impact on human hypothalamic neuron development remains unclear. Using human fetal GnRH neuroblasts (FNCB4) we investigated the effects of Cd exposure on their morpho-functional and developmental features. Cd induced oxidative stress and COX2 mRNA upregulation, indicative of inflammatory pathway activation, which was accompanied by reduced cell migration and downregulation of motility-related genes. These effects were associated with F-actin disassembly and altered expression of adhesion molecules. Electrophysiological analyses showed that Cd altered membrane potential, increased capacitance and permeability, and disrupted gap junctional communication, as also confirmed by connexin-43 delocalization. Moreover, Cd significantly reduced the expression of specific GnRH neuronal markers, suggesting impaired functional maturation. Overall, our findings provide the first evidence that Cd may interfere with mechanisms crucially involved in human GnRH neuron development, adding new mechanistic insights into the comprehension of how early-life exposure to Cd may contribute to fertility concerns. Full article

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and constitute a substantial economic burden. Despite population aging, recent years have witnessed an increasing prevalence of conditions such as heart failure (HF), including among young adults. In this context, coronary artery disease (CAD) has also become an increasingly discussed issue. It has long been recognized that control of risk factors is crucial for prevention. Researchers stress the need to monitor these factors from the earliest stages of life, and detailed analyses indicate an influence of the prenatal period on the development of chronic diseases, including cardiovascular disorders. Transgenerational and intergenerational epigenetic mechanisms are also taken into account. This review aims to systematically evaluate the existing literature and summarize the mechanisms that may link these factors. We consider epigenetic, metabolic, immunological, and inflammatory influences. We describe examples of environmental exposures, such as air pollution, maternal diet, toxins, and infections, and analyze data derived from clinical studies. We discuss gaps in the literature and identify limitations, outlining directions for future research and emphasizing the need for CVD prevention initiated at the earliest stages of life. Full article

Background and hypothesis: Per- and polyfluoroalkyl substances (PFAS) are highly persistent synthetic chemicals that can accumulate in renal tissue and potentially disrupt kidney function. Most prospective studies on PFAS–renal associations have focused on middle-aged or older adults, leaving uncertainty about whether similar patterns exist in younger populations. Methods: We investigated decade-long trajectories of plasma concentrations of 11 PFAS and their longitudinal associations with estimated glomerular filtration rate (eGFR) among 529 Taiwanese adolescents and young adults (aged 12–30 years) enrolled in the prospective YOung TAiwanese Cohort (YOTA), with measurements obtained in 2006–2008 and 2017–2019. Results: Nearly all plasma PFAS declined significantly over the 10-year period. Despite these reductions, higher baseline levels and greater annualized increases (Δln-PFAS/Δt) in linear perfluorooctanoic acid (PFOA), linear and branched perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) were consistently associated with larger eGFR gains over time (β = 0.33–0.40, q < 0.05). In complementary models using follow-up eGFR as the outcome, both baseline and cumulative PFAS changes (Δln-PFAS) remained positively associated with higher eGFR (β = 1.71–3.84, q < 0.05). Polynomial analyses further indicated mild non-linear exposure–response patterns for several PFAS, suggesting that renal effects may deviate from linearity across exposure ranges. The composite PFAS exposure index (mean of standardized ln-PFAS concentrations) was robustly associated with higher eGFR across sensitivity analyses excluding participants with chronic conditions. These associations were more pronounced among individuals with greater metabolic or physiological vulnerability. Conclusions: Higher PFAS exposure was associated with elevated eGFR in young adults, which may be consistent with early glomerular hyperfiltration or other renal hemodynamic alterations. These findings raise the hypothesis of early renal stress in early life and underscore the need for ongoing biomonitoring and longitudinal follow-up with additional kidney injury markers to clarify long-term renal consequences. Full article

Early life is a critical window for immune system development, during which the gut microbiome shapes innate immunity, antigen presentation, and adaptive immune maturation. Disruptions in microbial colonization—driven by factors such as cesarean delivery, antibiotic exposure, and formula feeding—deplete beneficial early-life taxa (e.g., Bifidobacterium, Bacteroides, and Enterococcus) and impair key microbial functions, including short-chain fatty acid (SCFA) production by these keystone species, alongside regulatory T cell induction. These dysbiosis patterns are associated with an increased risk of pediatric autoimmune diseases, notably type 1 diabetes, inflammatory bowel disease, celiac disease, and juvenile idiopathic arthritis. This review synthesizes current evidence on how the early-life microbiota influences immune maturation, with potential effects on the development of autoimmune diseases later in life. We specifically focus on human observational and intervention studies, where treatments with probiotics, synbiotics, vaginal microbial transfer, or maternal fecal microbiota transplantations have been shown to partially restore a disrupted microbiome. While restoration of the gut microbiome composition and function is the main reported outcome of these studies, to date, no reports have disclosed direct prevention of autoimmune disease development by targeting the early-life gut microbiome. In this regard, a better understanding of the early-life microbiome–immune axis is essential for developing targeted preventive strategies. Future research must prioritize longitudinal evaluation of autoimmune outcomes after microbiome modulation to reduce the burden of chronic immune-mediated diseases. Full article

Low social status leads to chronic social stress that predicts risk for physical and mental illness, especially when it starts early in life. To examine the longitudinal effects of low social status on the immune system, this study assessed the effects of low social status on developmental secretory patterns of pro- and anti-inflammatory markers under baseline conditions, as well as in response to an immune challenge (lipopolysaccharide (LPS)-induced activation of pro- and anti-inflammatory cytokines) in a translational rhesus monkey model of lifelong social subordination stress. Baseline blood samples were collected in 27 socially housed female rhesus monkeys (13 dominants, DOM, and 14 subordinates, SUB) during infancy (6 months), the juvenile pre-pubertal period (16 months), and adulthood (9–10 years) to examine the longitudinal effects of social status on inflammatory markers in unstimulated versus LPS-stimulated conditions mimicking exposure to bacterial infection. Basal levels of the stress hormone cortisol in blood were measured to examine associations between inflammation and activity of the hypothalamic–pituitary–adrenal (HPA) axis throughout the life span. Basal peripheral levels of inflammatory markers (e.g., IL-6) increased across development in both SUB and DOM animals with no significant differences. Basal cortisol levels were significantly higher in infancy as compared to adulthood, but no significant effects of social rank were detected. However, in adulthood, SUB animals showed a cytokine-specific immune response to ex vivo LPS stimulation with significantly higher secretions of IL-1β, IL-2, and IL-10 compared to DOM animals, whereas IL-8 response to LPS was lower in SUB animals than in DOMs. This cytokine-specific response to an immune challenge that mimics bacterial infection could reflect dysregulated immune cells that may have short-term adaptation, but at the cost of longer-term risks for low-grade chronic inflammation and accelerated immune aging for socially subordinate female macaques. Full article

Background and Objectives: Lung cancer in never-smokers (LCINS) has become a major global health concern, ranking as the fifth leading cause of cancer-related mortality. Unlike smoking-related lung cancer, LCINS arises from complex interactions between environmental carcinogens and distinct genomic alterations. This review summarizes current evidence on environmental risks, molecular features, and therapeutic progress shaping lung cancer management. Methods: A narrative review was conducted to examine risk factors for lung cancer in non-smokers. Studies reporting driver mutations in never-smokers and smokers were identified across major lung cancer histological subtypes, including small-cell lung cancer (SCLC), lung adenocarcinoma (LUAD), squamous cell carcinoma (SCC), and large-cell carcinoma (LCC). In addition, PubMed was searched for phase III trials and studies on targeted therapies related to driver mutations published between 2016 and 2025. Results: Environmental factors such as cooking oil fumes, radon, asbestos, arsenic, and fine particulate matter (PM_2.5) are strongly associated with LCINS through oxidative stress, DNA damage, and chronic inflammation. EGFR, PIK3CA, OS9, MET, and STK11 mutations are characteristic of never-smokers, in contrast to TP53 mutations, which are more common in smokers. Recent advances in targeted therapy and immunotherapy have improved survival and quality of life, emphasizing the importance of molecular profiling for treatment selection. Conclusions: LCINS represents a distinct clinical and molecular entity shaped by complex interactions between environmental exposures and genetic susceptibility. Genetic alterations promote tumor immune evasion, facilitating cancer development and progression. Continued advances in air quality control, molecular diagnostics, and precision therapies are essential for prevention, early detection, and reduction of the global disease burden. Full article

Background/Objectives: Pediatric cancer survivors frequently experience neuromuscular sequelae related to chemotherapy-induced neurotoxicity. Agents such as vincristine, methotrexate, and platinum compounds can lead to persistent gait alterations and sensorimotor deficits that impair mobility and quality of life. This study aimed to objectively assess gait in pediatric cancer survivors after the completion of oncological pharmacological treatment to identify specific spatiotemporal, kinematic, and kinetic alterations and characterize neuromechanical patterns associated with neurotoxic exposure. Methods: A cross-sectional observational study was conducted including pediatric cancer survivors (6–18 years) who had completed chemotherapy and age- and sex-matched healthy controls. Gait was analyzed using a Vicon^®3D motion capture system, with reflective markers placed on standardized anatomical landmarks. Spatiotemporal, kinematic, and kinetic variables were compared between groups using parametric tests and statistical parametric mapping (SPM) with Holm–Bonferroni correction (α = 0.05). Results: Pediatric cancer survivors showed slower gait velocity (Mean Difference (MD) = 0.17, p = 0.018, Confidence Interval CI95% = 0.04; 0.4), shorter step (MD = 0.1, p = 0.015, CI95% = 0.01; 0.19) and stride length (MD = 0.17, p = 0.018, CI95% = 0.03; 0.31), as well as reduced single support time (MD = 0.1, p = 0.043, CI95% = 0.01; 0.19), along with significant alterations in pelvic, hip, knee, and ankle kinematics compared with controls. Increased pelvic elevation (MD = 0.92, p = 0.018, CI95% = 0.25; 1.58), reduced hip extension during stance (MD = −2.99, p = 0.039, CI95% = −5.19; −0.74), knee hyperextension in mid-stance (MD = −3.84, p < 0.001, CI95% = −6.18; −0.72), and limited ankle dorsiflexion (MAS MD = −4.04, p < 0.001, CI95% = −6.79; −0.86, LAS MD = −3.16, p < 0.001) and plantarflexor moments in terminal stance (MAS MD = −149.65, p = 0.018, CI95% = −259.35; −48.25, LAS MD = −191.81, p = 0.008, CI95% = −323.81; −57.31) were observed. Ground reaction force peaks during loading response (MAS MD = −16.86, p < 0.001, CI95% = −26.12; −0.72 LAS MD = −11.74, p = 0.001, CI95% = −19.68; −3.94) and foot-off (MAS MD = 10.38, p = 0.015, CI95% = 0.41; 20.53, LAS MD = 11.88, p = 0.01, CI95% = 3.15; 22.38) were also reduced. Conclusions: Children who have completed chemotherapy present measurable gait deviations reflecting persistent neuromechanical impairment, likely linked to chemotherapy-induced neurotoxicity and deconditioning. Instrumented gait analysis allows early detection of these alterations and may support the design of targeted rehabilitation strategies to optimize functional recovery and long-term quality of life in pediatric cancer survivors. Full article

Pervasive microplastics (MPs) and per- and polyfluoroalkyl substances (PFAS) frequently co-occur across aquatic and terrestrial environments due to shared sources, transport pathways, and persistence, yet their interaction-driven effects on environmental fate, bioavailability, and toxicity remain incompletely resolved. This review critically synthesizes current knowledge on the environmental co-occurrence of MPs and PFAS, the physicochemical mechanisms governing their interactions, and the resulting ecological and toxicological consequences across aquatic, terrestrial, and biological systems. Emphasis is placed on sorption and desorption processes; environmental modifiers such as pH, salinity, dissolved organic matter (DOM), and aging; and biological responses under combined exposure scenarios. Across laboratory and field studies, MPs–PFAS co-exposure is frequently associated with altered PFAS partitioning and enhanced organismal uptake, with reported bioaccumulation increases of up to ~2.5-fold relative to PFAS-only exposures. These changes are often accompanied by amplified oxidative stress, immune dysregulation, metabolic disturbance, and reproductive impairment, particularly in aquatic invertebrates and early life stages of fish. Evidence further indicates that the magnitude and direction of combined effects depend on polymer type, particle size, surface aging, and biological context, underscoring the highly system-specific nature of MPs–PFAS interactions. By integrating findings from environmental monitoring, laboratory toxicology, and mechanistic and modeling studies, this review identifies key knowledge gaps related to nanoplastics detection, environmentally realistic exposure conditions, sorption reversibility, and mixture toxicity assessment. Collectively, these insights highlight limitations in current single-contaminant risk frameworks and underscore the importance of incorporating MPs-mediated PFAS transport and bioavailability into exposure assessment and regulatory evaluation. Full article

Lipid raft-associated gangliosides facilitate the early stages of SARS-CoV-2 entry by triggering the exposure of the receptor-binding domain (RBD) within the trimeric spike protein, which is initially sequestered. A broad range of in silico, cryoelectron microscopy and physicochemical approaches indicate that the RBD becomes accessible after a ganglioside-induced conformational rearrangement originating in the N-terminal domain (NTD) of one protomer and propagating to the neighboring RBD. We previously identified a triad of amino acids, Q134-F135-N137, as a strictly conserved element on the NTD. In the present review, we integrate a series of structural and experimental data revealing that this triad may act as a conformational transducer connected to a chain of residues that are capable of transmitting an internal conformational wave within the NTD. This wave is generated at the triad level after physical interactions with lipid raft gangliosides of the host cell membrane. It propagates inside the NTD and collides with the RBD of a neighboring protomer, triggering its unmasking. We also identify a chain of aromatic residues that are capable of controlling electron transfer through the NTD, leading us to hypothesize the existence of a dual conformational/quantum wave. In conclusion, the complete conservation of the Q134-F135-N137 triad despite six years of extensive NTD remodeling underscores its critical role in the viral life cycle. This triad represents a potential Achilles’ heel within the hyper-variable NTD, offering a stable target for therapeutic or vaccinal interventions to disrupt the conformational wave and prevent infection. These possibilities are discussed. Full article