Search Results (4,739)

Background: Evidence regarding long-term outcomes among offspring following maternal or paternal exposure to BCR::ABL1 tyrosine kinase inhibitors (TKIs) is limited. We described pregnancy outcomes and offspring health through adolescence and early adulthood in a single-centre cohort of patients with chronic myeloid leukemia (CML). Methods: This retrospective, descriptive cohort study included patients with chronic-phase CML who experienced a pregnancy, or whose partner experienced a pregnancy, in association with TKI exposure and for whom longitudinal offspring follow-up was available. Long-term offspring outcomes were ascertained from detailed obstetric and pediatric medical records supplemented by parental reports. Fourteen patients (nine women and five men) contributed 21 pregnancy events and 23 live-born offspring, including two twin pregnancies in the paternal-exposure group. Results: In the maternal-exposure group, median gestational age at delivery was 38.0 weeks (range, 35–40), and four of 15 deliveries were preterm. In the paternal-exposure group, median gestational age was 39.0 weeks (range, 38–41), with no preterm deliveries. Median offspring follow-up was 252 months (range, 212–295), extending through adolescence and into early adulthood. One offspring had a primum atrial septal defect that was surgically corrected. No additional clinically documented major abnormalities in growth or developmental progress were identified during available follow-up. Given the small cohort, these observations were interpreted descriptively and were not considered evidence of equivalence with population-level rates. Conclusions: This small retrospective cohort provides unusually long observational follow-up of offspring after selected maternal or paternal TKI exposures. The findings are clinically informative but cannot establish reproductive safety or exclude rare adverse outcomes. Larger multicentre registries using standardized long-term developmental, neurocognitive, and endocrine assessments are needed. Full article

3-Nitropropionic acid (3-NPA) is an irreversible inhibitor of succinate dehydrogenase (SDH; mitochondrial complex II) that is widely used to model mitochondrial metabolic stress. Direct reproductive studies now show that 3-NPA can increase ovarian oxidative stress, granulosa-cell apoptosis, follicular atresia, alter ovarian reserve, impair oocyte maturation, and reduce fertility in experimental models. However, no ovarian study has yet demonstrated the complete succinate–HIF-1α–NLRP3 cascade proposed here. We therefore propose a testable framework in which SDH inhibition causes succinate accumulation and impaired respiratory electron flux, while redox stress provides an additional signal for HIF-1α stabilization and NLRP3 activation. Succinate-mediated inhibition of prolyl hydroxylases provides a mechanistic route to HIF-1α stabilization under normoxic or near-normoxic conditions, whereas NLRP3 activation may integrate mitochondrial danger signals with inflammatory signaling. Importantly, HIF-1α is not intrinsically pathogenic in the ovary: physiological HIF-1α signaling supports angiogenesis, ovulation, granulosa-cell survival, autophagy, and luteal remodeling, whereas persistent or excessive activation may become maladaptive. We further refine the proposed metabolic–inflammatory threshold as a measurable state in which combined succinate/redox burden and inflammasome activation exceed the adaptive capacity of a follicular unit. The model predicts that time-resolved measurements of succinate, SDH activity, HIF-1α stabilization, NLRP3 activation, and follicular outcomes should reveal ordered relationships that can be tested by pharmacological and genetic intervention. This review distinguishes direct ovarian evidence from cross-system mechanistic evidence and identifies the experiments required to establish causality. Full article

Aquaculture has become the fastest-growing food-production sector worldwide, with increasing reliance on plant-based feed ingredients such as maize, soybean, wheat, rice, and oilseed meals. Although these ingredients reduce dependence on fishmeal, they are highly susceptible to fungal contamination and subsequent mycotoxin production. Global surveys reveal widespread contamination of aquafeeds with major regulated mycotoxins, including aflatoxins, fumonisins, deoxynivalenol, zearalenone, ochratoxin A, and T-2 toxin, alongside emerging toxins such as enniatins, beauvericins, and sterigmatocystin metabolites. Aflatoxin B₁ is the most prevalent and toxic mycotoxin, with contamination prevalence often exceeding 80–100% in Africa and Asia with contamination levels surpassing 400 µg/kg in some regions of these continents. Fumonisins, deoxynivalenol, and zearalenone are also commonly detected, with fumonisins levels occasionally exceeding 7000 µg/kg. Mycotoxins induce diverse toxic effects in fish, including growth suppression, hepatotoxicity, nephrotoxicity, immunosuppression, oxidative stress, reproductive dysfunction, and mortality. Collectively, these findings highlight the urgent need for improved surveillance, feed management, and harmonized regulations addressing multi-mycotoxin exposure to safeguard aquaculture productivity, fish, and public health. This review synthesizes current knowledge on the global mycotoxin contamination patterns, analytical detection methods in fish feed and processed seafood as well as the toxicological effects of mycotoxins, with emphasis on species-specific responses and food safety implications. Full article

Background: Women with chronic medical conditions are at increased risk of adverse pregnancy outcomes, making contraceptive counselling an essential component of comprehensive chronic disease management. However, evidence regarding the knowledge and clinical practices of non-obstetric physicians remains limited. This study evaluated physicians’ knowledge, attitudes, and practices regarding contraceptive counselling for women with chronic medical conditions in a tertiary referral hospital in Türkiye. Methods: A cross-sectional Knowledge–Attitude–Practice survey was conducted among 264 non-obstetric physicians at İzmir City Hospital between July and October 2025. The questionnaire assessed contraceptive counselling practices, awareness of the World Health Organization Medical Eligibility Criteria for Contraceptive Use (WHO MEC), postgraduate contraception training, perceived barriers, and educational needs. Categorical associations were examined using chi-square or exact procedures as appropriate, and multivariable binary logistic regression was performed to evaluate factors associated with self-reported routine contraceptive counselling while accounting for potential confounding. Results: Among the 260 physicians who responded to the relevant item, 89.2% agreed that contraceptive method selection may influence the course of chronic disease, whereas 37.9% of the total sample reported routinely providing contraceptive counselling. Awareness of the WHO MEC was limited, with 75.8% reporting no prior awareness, and 18.2% had received postgraduate contraception training. In the adjusted analysis, WHO MEC awareness (aOR = 2.76, 95% CI: 1.39–5.46; p = 0.004), postgraduate contraception training (aOR = 2.38, 95% CI: 1.12–5.07; p = 0.024), seeing ≥30 women of reproductive age per week (aOR = 2.07, 95% CI: 1.15–3.73; p = 0.016), female sex (aOR = 3.81, 95% CI: 1.90–7.65; p < 0.001), and >10 years of clinical practice (aOR = 2.38, 95% CI: 1.23–4.62; p = 0.010) were associated with higher odds of self-reported routine counselling. Specialty was not significantly associated after adjustment. Conclusions: Self-reported routine contraceptive counselling remained limited despite broad recognition of the relevance of contraception in chronic disease care. Guideline awareness, postgraduate training, clinical exposure, sex, and clinical experience were associated with routine counselling after adjustment, although causal relationships cannot be inferred from this cross-sectional study. These findings support further evaluation of educational and organizational strategies for integrating reproductive healthcare into chronic disease management. Full article

Background/Objectives: Obesity and excessive gestational weight gain (EGWG) are known risk factors for adverse outcomes in pregnancy, but the comparative risk is less well defined and increasingly relevant in an era of increasing use of weight loss medications. We aimed to determine whether EGWG was associated with adverse maternal and neonatal outcomes, compared with prepregnancy obesity. Methods: Multicenter retrospective cohort study of pregnant patients who delivered a singleton within a single university health system from 2019–2024. Patients with missing prepregnancy body mass index (BMI) data, BMI < 18.5 kg/m², or pregestational diabetes were excluded. Logistic regression with propensity score weights and g-computation were used to evaluate if the incidence of several adverse maternal and neonatal outcomes were impacted by prepregnancy obesity and gestational weight gain (GWG). p values were adjusted for multiple comparisons. Results: Among the 129,615 pregnancies included, 28,516 (22.0%) had prepregnancy obesity, 36,943 (28.5%) were overweight prior to pregnancy, and 64,156 (49.5%) had a normal BMI prior to pregnancy. When compared to patients with obesity, patients with normal prepregnancy BMI and EGWG had a lower risk of adverse maternal and neonatal outcomes, including gestational diabetes, gestational hypertension, preeclampsia, eclampsia, cesarean delivery, and postpartum hemorrhage, as well as large and small for gestational age birthweight, stillbirth, neonatal intensive care unit admission, neonatal mechanical ventilation, respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis. Beneficial effects were attenuated for patients with overweight prepregnancy BMI or for larger EGWG. Conclusions: Lower prepregnancy BMI, even with the potential unintended consequence of EGWG, may be more favorable than untreated prepregnancy obesity with regard to perinatal outcomes. Full article

Chlorpyrifos (CPF) is the most commonly used organophosphorus insecticide in agriculture globally. This has raised concerns due to its persistence, bioaccumulation, neurotoxicity, and environmental and human health effects. Until 2020, CPF was the most commonly used pesticide in European Union (EU) food production. CPF is also used in other parts of the world, though it has been discontinued in the EU, as national pesticide surveillance programs indicate it is found in soil, water, and food. This type of persistence is potentially harmful to farmers, consumers, and animals because CPF is toxic. Markedly, CPF has the potential to change the microbiota composition of soils, i.e., fungal, bacterial, and actinomycete communities, and inhibit the mineralization of nitrogen. The key CPF activity is associated with the inhibition of acetylcholinesterase (AChE), leading to reproductive, neurotoxic, and genotoxic effects. Microbial degradation, especially when applied by means of bacteria, has become one of the promising alternatives to the traditional physicochemical means since it is inexpensive, does not harm the environment and may possibly be fully detoxified. This review summarizes the latest developments in the study of CPF-degrading bacteria, enzyme pathways, microbial diversity, and the evaluation of the environmental impact of microbial remediation. Recent research findings, genomic research developments, and potential applications of CPF-degrading bacteria are addressed. In addition, this study reveals the current knowledge gaps, presents biotechnological challenges, and suggests future directions in the application of field-scale studies, focusing on the application of microbial solutions in sustainable agriculture. Full article

California’s Proposition 65 requires warning labels for chemicals associated with carcinogenicity or reproductive toxicity, affecting global cosmetic and fragrance formulations. While safrole has an established safe harbor level (No Significant Risk Level, NSRL) of 3 µg/day, its structural analogues, estragole and methyleugenol, lack specific safe harbor thresholds. To address this data gap using non-animal methodologies, this study evaluated a Next-Generation Risk Assessment (NGRA) workflow combining read-across and in silico modeling. Structural, physicochemical, and skin-permeation profiling supported category homogeneity (Tanimoto Tc ≥ 0.82 and comparable log Kp values) in accordance with OECD and ECHA guidelines. Multi-platform QSAR consensus (ToxTree, Danish QSAR, and VEGA QSAR) indicated that while parent phenylpropenes lack direct bacterial mutagenicity, they share a hepatic bioactivation pathway leading to mammalian clastogenicity and carcinogenicity predictions. Molecular docking with human Cytochrome P450 1A2 (CYP1A2; PDB: 2H14) identified safrole as the category’s conservative toxicological benchmark, exhibiting the highest binding affinity (−8.026 kcal/mol) and closest proximity to the catalytic HEME iron. Consequently, applying safrole’s 3 µg/day NSRL to estragole and methyleugenol provides a quantitative threshold to evaluate consumer exposure in cosmetic products, ensuring public health protection and regulatory compliance. Full article

Tumor angiogenesis plays a critical role in cancer growth and metastatic progression and therefore represents an important therapeutic target. Bee venom-derived peptides constitute a diverse source of bioactive molecules whose interactions with angiogenesis-associated receptors remain incompletely characterized. In this study, an integrated in silico workflow was applied to investigate the potential interactions of selected bee venom peptides, including melittin and tertiapin, with major angiogenic-associated receptors, including platelet-derived growth factor receptor alpha (PDGFR-α), vascular endothelial growth factor receptors, fibroblast growth factor receptors, and integrin αvβ3. Molecular docking was used to identify and prioritize potential peptide–receptor complexes, while molecular dynamics simulations were performed to assess their conformational stability and interaction patterns under the simulated conditions. Reactome pathway enrichment analysis was subsequently used to contextualize the selected molecular targets within angiogenesis-related biological processes. Melittin–PDGFR-α and tertiapin–integrin αvβ3 emerged as the highest-ranked complexes and exhibited relatively stable interaction patterns with persistent intermolecular contacts throughout the simulations. Pathway enrichment analysis further associated the investigated targets with PDGFR signaling, cell migration, and other angiogenesis-related processes. Collectively, these findings suggest that melittin–PDGFR-α and tertiapin–integrin αvβ3 represent promising peptide–receptor pairs for further investigation while providing a computational rational for exploring bee venom peptides as potential modulators of tumor angiogenesis. However, these findings should be considered hypothesis-generating and primarily serve to prioritize peptide-receptor pairs for future experimental validation, including binding assays, cellular assays, and relevant in vivo studies. Peptide selectivity, toxicity, stability, and targeted delivery should also be evaluated before any therapeutic application can be considered. Full article

Mastitis remains one of the most important infectious diseases affecting dairy cows, with substantial consequences for animal health, milk production, and farm profitability. In this study, we extend a nonlinear SIRS–P compartmental model for mastitis transmission in dairy cows by incorporating sensitivity analysis, optimal control, and cost-effectiveness analysis. The model consists of susceptible, infected, and recovered cow populations together with an environmental pathogen compartment, and accounts for direct cow-to-cow transmission, indirect transmission through environmental contamination, recovery, recurrence of infection, recruitment, and culling. A sensitivity analysis of the basic reproduction number $R_0$ is performed to identify the parameters that most strongly influence mastitis transmission. An optimal control problem is then formulated using time-dependent controls that reduce direct transmission, reduce environmental contamination, and enhance recovery. Pontryagin’s Maximum Principle is applied to derive the optimality system, which is solved numerically using the forward–backward sweep method. Seven intervention strategies are compared through numerical simulations and cost-effectiveness analysis using ACER and ICER. The results indicate that the fully integrated strategy $S_7$, which combines prevention and screening, environmental sanitation, and treatment, provides the largest overall disease reduction. However, Strategy $S_1$, based on direct transmission reduction, offers the most cost-effective allocation of resources for reducing the mastitis infection burden. Full article

Aquaculture is a field that has developed rapidly over the past decade with the emergence of intensive farming systems that have significantly increased global fish production. However, this intensification has also led to the emergence of diseases caused by various pathogens, often resulting in extensive antibiotic use and, consequently, antimicrobial resistance (AMR). Consequently, research has focused on finding other sustainable alternatives to avoid the overuse of antibiotics and to protect both human and animal health. Probiotics and prebiotics have been extensively studied for their wide range of effects on growth, immunity, and the control of various pathogens. Through their complex mechanisms, they can also improve water quality, mitigate the effects of various physicochemical stressors, and enhance reproduction. This review aims to present the evolution of these concepts, with an emphasis on their effects, which often vary depending on the type of additive used, the dose, and the fish species. Full article

The Polish Konik horse (PKH) is one of Europe’s best-known native conservation breeds. Traditionally associated with the extinct Eurasian tarpan and conservation grazing, the breed has recently become the subject of multidisciplinary research encompassing genetics, ecology, health, behaviour and reproduction. This narrative review summarises current knowledge on the biological characteristics and contemporary scientific significance of the PKH. Literature published between 2005 and 2026 was identified through searches of PubMed, Scopus, Web of Science and Google Scholar and narratively synthesised. Available evidence suggests that, despite severe historical bottlenecks, the PKH has retained considerable genetic diversity and its characteristic maternal and paternal founder-line structure. Recent molecular studies have revised traditional concepts of the breed’s origin, while ecological research supports its important role in conservation grazing and wetland restoration. Behavioural and reproductive studies indicate stable temperament, high reproductive efficiency and adaptation to extensive management systems. However, current knowledge is derived predominantly from observational studies, with relatively few comparative investigations and limited genomic and longitudinal data. The PKH represents a valuable model for research on conservation genetics, environmental adaptation, animal welfare, reproductive biology and ecosystem management. Further interdisciplinary studies are needed to strengthen the evidence base for conservation and breeding strategies. Full article

Background: Research on women’s health is essential for addressing sex-specific healthcare needs and informing evidence-based policy. However, women-only health research in Taiwan has not been systematically examined. Methods: We conducted a Scopus-based bibliometric analysis of health research exclusively involving female populations in Taiwan from 2015 to 2025. We included English-language, peer-reviewed journal articles involving only female participants and conducted in Taiwan or using Taiwanese datasets. Mixed-sex studies, including those reporting female-specific or sex-stratified findings, were excluded. Publication trends, citations, international collaboration, secondary data sources, and thematic patterns were analyzed using Biblioshiny and VOSviewer. Results: A total of 1345 publications across 446 journals were included. Publication output increased from 126 articles in 2015 to a peak of 153 in 2021, followed by a decline, with an annual growth rate of −0.4%. The publications involved 3412 authors and received an average of 14.52 citations per document. International co-authorship accounted for 19.48% of publications, with the United States as the leading collaborator. The National Health Insurance Research Database was the most frequently reported secondary data source (n = 371, 27.6%). Research was concentrated in cancer, reproductive health, and mental health, whereas cardiovascular health accounted for a comparatively smaller share of the literature. Conclusions: Women-only health research in Taiwan remained active throughout the study period, despite a decline in publication output after 2021. The extensive use of national health databases and international collaboration further characterized the research landscape. These findings provide an evidence-informed basis for future research priority-setting, including efforts to broaden research across women’s health conditions and life-course stages while considering research activity alongside population health needs. Integrating bibliometric evidence with population health priorities may support a more balanced and comprehensive women’s health research agenda in Taiwan. Full article

Endocrine system hormones regulate growth, metabolism, and reproduction. These hormones often function at low concentrations, making them especially susceptible to disruption via endocrine-disrupting chemicals (EDCs) that can mimic, block, or disturb normal hormone signaling. Among these EDCs, polychlorinated biphenyls (PCBs) and per- and polyfluoroalkyl substances (PFAS) are of special concern for human health because they are persistent and bioaccumulate. In this review, we focus on effects of PCBs and PFAS on female reproduction, with emphasis on steroidogenesis, ovarian function, fertility, and assisted reproductive technology (ART) outcomes. We describe the chemical properties and exposure routes of PCBs and PFAS, and how these features explain their long half-lives and ability to transfer to the female reproductive system and fetus. Evidence suggests that both PCBs and PFAS can reduce follicle numbers, disturb oocyte quality, and increase oxidative stress and apoptosis. Human and animal data also link PCB and PFAS exposure with altered ART outcomes. Together, the literature indicates that persistent exposure to PCBs and PFAS poses a significant and long-lasting risk to female reproductive health. Full article

Background: Opioid use during pregnancy is linked to preterm birth, fetal growth restriction, and Neonatal Opioid Withdrawal Syndrome. While the placenta is the primary regulator of the uterine environment, the precise molecular mechanisms by which opioids dismantle placental function remain poorly defined. Methods: The transcriptomic landscape of opioid-exposed human placentas from a unique Hawai’i-based cohort was characterized. Results: Transcriptional signatures were defined by genes involved in translational inhibition and metabolic attenuation. Integrative network modeling predicted a prominent stress-signaling hub centered on p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Related Kinase 1/2, paralleling a broad suppression of ribosomal protein transcripts (Ribosomal Protein 27S, -29, and -39). This response was further characterized by the inhibition of the Myelecytomatosis Proto-Oncogene regulatory hub, predicting a loss of mitochondrial phosphate transport through associated genes (via Solute Carrier Family 25A3) and cell-cycle progression (via S-Phase Kinase-Associated Protein 1). Additionally, the genes in this model suggested upregulation of antisense regulatory brakes, such as RAP2C Antisense RNA 1, which might further reinforce this inhibitory state. Conclusion: The findings suggest that prenatal opioid exposure is associated with the disruption of placental homeostasis. This may be coordinated by protein synthesis and bioenergetic flux, as inferred from the modeled eukaryotic Translation Initiation Factor-mediated Integrated Stress Response. These findings establish a localized, clinical baseline of human placental stress, highlighting candidate molecular regulatory nodes to guide future mechanistic studies and biomarker discovery in exposed pregnancies. Full article

Glyphosate is an herbicide used to control plant growth and ripen specific crops. Glyphosate exposure has been associated with cancer, metabolic and neurological diseases, and reproductive issues in humans. A common element linking these disorders could be vitamin D deficiency. However, the relationship between glyphosate exposure and vitamin D status in the general population remains unclear. This analysis focused on the association between urinary glyphosate levels and serum 25-hydroxy vitamin D [25(OH)D] concentrations in a large representative sample of U.S. adults. Data from 4284 participants in the National Health and Nutrition Examination Survey (NHANES) between 2013–2018 were analyzed. Serum 25(OH)D levels were modeled using multivariable weighted linear regression, with adjustment for age, sex, race/ethnicity, body mass index, season, education, income, physical activity, smoking, and kidney function. Urinary glyphosate concentration was inversely associated with serum 25(OH)D in both the design-based univariate weighted analysis (β = −3.537, p = 0.035) and adjusted survey-weighted models for major confounding factors (β = −4.208, p = 0.009), using Taylor linearization for variance estimation to account for the complex NHANES survey design. In stratified analysis, the relationship between total vitamin D intake and serum 25(OH)D was found to be significantly modified by glyphosate exposure, with stronger dietary dependence observed in the high-exposure tertile (β = 12.88, p < 0.0066) than in the low-exposure tertile (β = 7.41, p < 0.0165). Higher urinary glyphosate concentration was associated with lower serum 25(OH)D levels in U.S. adults, suggesting it may represent an unrecognized risk factor for vitamin D deficiency. Longitudinal and experimental studies are needed to clarify causality, the underlying mechanisms, and public health implications. Full article