Search Results (419)

Coccidioidal meningitis (CM) is a rare but life-threatening complication of disseminated coccidioidomycosis, occurring in ~16% of cases, particularly among children in endemic regions such as the southwestern US and northern Mexico. Without timely diagnosis and antifungal therapy, pediatric CM is almost universally fatal within the first year. Hydrocephalus develops in up to 50% of cases. In 2000, Galgiani et al. established fluconazole as first-line therapy for CM. Subsequent guidelines refined management but did not specifically address pediatric patients (>1 month–≤19 years). No studies in the fluconazole era have systematically evaluated risk factors for complications in this population. We therefore conducted a systematic review and proportional synthesis of pediatric CM cases, focusing on CNS complications and outcomes. PubMed/MEDLINE, Embase (Ovid), and Web of Science were systematically searched (2000–2025). PROSPERO registration ID (1130290). Inclusion criteria encompassed epidemiological studies, case series, and case reports that described at least one pediatric case of CM or CNS involvement, confirmed by diagnostic methods. Cases in adults, neonates (<1 month), congenital infections, teratogenicity studies, reviews, or incomplete reports were excluded. Only cases with complete individual data (n = 48) were included. Methodological rigor was ensured using JBI Critical Appraisal Tools. Of 1089 studies, 31 met the inclusion criteria, representing 3874 pediatric cases. CM/CNS involvement was confirmed in 165 cases (4.25%; 95% CI: 3.6–4.9%), with hydrocephalus in 62 (37.5%). Among 48 case reports with complete data, fluconazole was first-line therapy in 65%. Serum CF titers ≥ 1:16 were associated with hydrocephalus plus stroke (p = 0.027) and independently predicted adverse outcomes (relapse/death; OR = 4.5, p = 0.037), whereas lifelong azole therapy was associated with improved outcomes (overall survival mean, 82 vs. 32 months; p = 0.002). Pediatric CM remains highly lethal, with hydrocephalus a frequent and severe complication. High serum CF titers (≥1:16) predict poor outcomes, emphasizing the urgent need for standardized, pediatric-specific diagnosis and management guidelines. Full article

Healthcare waste (HCW) represents a growing yet frequently underestimated threat to public health, due to its complex toxicological profile. Exposure to HCW has been associated with a broad spectrum of adverse effects, including infections of bacterial, viral, or fungal origin, as well as systemic consequences such as endocrine disruption, metabolic disturbances, and mutagenic, carcinogenic, or teratogenic outcomes. These risks are particularly elevated among healthcare professionals and waste management personnel, who are directly exposed to hazardous materials. This narrative review aims to consolidate current knowledge on the toxic potential of HCW, emphasizing the variability of risks according to waste category and point of origin. A critical reevaluation of the toxicity–health risk–waste management triad is needed to strengthen preventive and protective strategies in both clinical and waste-handling settings, and the review is therefore structured around targeted questions along this axis. Priority should be given to waste prevention, minimization, and segregation at source, as downstream treatment processes may introduce additional hazards. Each category of hazardous HCW exhibits specific mechanisms of toxicity, underlining the importance of targeted and informed management approaches. Future directions should include enhanced training for waste handlers, the development of unified regulatory frameworks, and improved international data collection and reporting systems. Strengthening these components is essential for reducing occupational and environmental health risks and ensuring safer conditions across healthcare systems. Full article

Cannabis is one of the most studied psychoactive substances due to its increasing prevalence and evolving legal status. Of particular concern is the rising consumption among young individuals, where excessive use may disrupt reproductive processes and pose long-term health risks to offspring. This narrative review examines the effects of cannabis use on male and female reproductive health, including its impact on male fertility, the female reproductive system, placental function, and prenatal and postnatal outcomes, as well as fetal development. A nonsystematic review was conducted using PubMed, Scopus, Web of Science, and Google Scholar databases in November 2024. After screening titles and abstracts and the full-text analysis, 64 studies were included in this narrative review. In men, cannabinoids can interfere with spermatogenesis, reduce sperm motility and quality, and lower testosterone levels, as demonstrated in clinical and experimental studies. In women, cannabinoid-induced disorders include negative effects on ovarian follicle maturation, ovulation, placental function, and prenatal development. Prenatal exposure to cannabis is associated with the risk of reduced birth weight, birth defects, sudden infant death syndrome (SIDS) or lactation problems due to the penetration of cannabis metabolites into breast milk. The findings highlight the potential negative effects of cannabis on reproductive health and fetal development. Given these risks, individuals attempting to conceive, and pregnant women should be advised against cannabis use. Greater awareness is needed among healthcare professionals and the public regarding the reproductive risks associated with cannabis consumption. While the evidence on teratogenic effects is not always conclusive, caution should be exercised, and further research is essential to deepen the understanding of these effects. Full article

Congenital developmental defects are among the postnatal consequences of early exposure to hydrogen peroxide or other teratogens that induce oxidative stress, highlighting a potential mechanistic link between oxidative stress, redox signaling, and developmental processes. This study evaluated the morphological and behavioral abnormalities induced by hydrogen peroxide in the Drosophila melanogaster model, as well as its teratogenic index. The results demonstrated that hydrogen peroxide induces morphological abnormalities in adult wings, legs, and abdomen, as well as necrosis and developmental disruptions during larval and pupal stages. A median lethal concentration (LC₅₀) of 0.16% and a teratogenic index (TI) of 0.44 were calculated when considering anomalies at any development stage; a TI of 0.21 was obtained when considering only adult abnormalities. Regarding behavioral changes, an increase in locomotor activity was observed in both larvae and adults, with significantly greater activity recorded in adult females than in males. These findings suggest that hydrogen peroxide can induce both morphological and behavioral abnormalities in D. melanogaster, although it presents a low teratogenic index. Full article

Fetal exposure to antiseizure medications (ASMs) can impact organogenesis, resulting in elevated risk of congenital malformations. Despite longstanding clinical awareness of the teratogenic potential of ASMs, the molecular mechanisms remain largely unexplored. To address this multisystem impact of ASMs, an OMIC-based approach was considered to understand the impact of ASMs on methylome and subsequently on proteome and how folic acid (FA) supplementation can counter the teratogenic impact. The study employed an established in vitro embryonic cell line model system, treated with varying concentrations of first-generation ASMs, alone and in combination with FA. Integrated analyses included quantification of global DNA methylation, expression analysis of key epigenetic regulators (DNMTs and TETs), genome-wide methylation profiling using the 935K EPIC array, and LC-MS/MS-based proteomics analysis. The study identified that ASMs can induce global DNA hypomethylation, which was likely to be impacted by dysregulation of DNMT and TET expression. Interestingly, FA co-treatment partially restored DNA methylation as evidenced by global DNA methylation and epigenetic gene expression, and also by compensatory effect via one-carbon metabolism. Genome-wide DNA methylation revealed site-specific hypermethylation at key developmental genes, several of which were reversed with FA. Proteomics analysis identified downregulation of developmentally critical proteins, including those linked to key metabolic processes, while FA co-treatment reversed expression of several such proteins. Integrative methylome–proteome analysis revealed the coordinated regulation of target genes that are linked to congenital abnormalities. Together, these findings offer mechanistic insight into ASM-induced teratogenesis and support FA’s potential to mitigate epigenetic and proteomic disruptions. This integrated OMICs based approach identifies key biomarkers which can be used for therapeutic monitoring and help in optimizing maternal epilepsy management. Full article

Pyridine is a recalcitrant organic compound present in industrial wastewater that causes severe effects on the environment and the health of living beings, as it is considered a toxic, mutagenic, teratogenic, and carcinogenic agent. Therefore, this research explored the efficacy of a zinc oxide catalyst, doped with platinum nanoparticles and supported alumina through the precipitation method, for the photocatalytic degradation of pyridine using a fluidized bed reactor. A Box–Behnken experimental design was used to analyze the effect of the pH (4–10), the pyridine concentration (20–300 ppm), and the amount of catalyst (20–100 g). The X-ray diffraction (XRD) characterization results confirmed the hexagonal structure of the zinc oxide and the successful incorporation of platinum. Scanning electron microscopy (SEM) revealed a nano-bar morphology upon catalyst doping, favoring the photocatalytic activity. Pyridine removal of 57.7% was achieved under the following conditions: a pH of 4, 160 ppm of pyridine, and 100 g of catalyst. The process followed a pseudo-first-order model, obtaining the reaction constant k₁ = 1.943 × 10⁻³ min⁻¹ and the adsorption constant k₂ = 1.527 × 10⁻³ L/mg. The results showed high efficiency and stability of the catalyst in the fluidized bed reactor for pyridine degradation, especially under acidic conditions, representing a promising technological alternative for treating industrial wastewater contaminated with N-heterocycles such as pyridine. Full article

In this paper, a toxicological investigation was carried out on a series of azoic direct dyes generally with an affinity for cellulosic fibers, presenting symmetrical and asymmetrical structures having as a central component a non-carcinogenic, mutagenic, or teratogenic and accessible precursor potential substitute for benzidine, namely 4,4′-diaminobenzanilide, and, as coupling components, 2-hydroxybenzoic acid, 2-hydroxy-3,6-naphthalenesulfonic acid, 2-amino-8-hydroxynaphthalene-6-sulfonic acid, 1-amino-8-hydroxynaphthalene-3,6-disulfonic acid, 1-(4′-sulfophenyl)-3-methyl-5-pyrazolone, and 2-hydroxy-6-naphthalenesulfonic acid, respectively. For the purpose of their safe use, this study shows the results regarding the toxicity of the above-mentioned dyes, obtained through biological tests on colonies of Hydractinia echinata (H. echinata). The toxicity tests were performed on heterotrophic bacteria cultures obtained from the Bega River. The minimum toxic concentration was monitored using the dilutions 0.6 g/L, 24 g/L, and 48 g/L, obtained by dilution of a stock solution of 60 g/L. The symmetric dye with the coupling component 2-hydroxybenzoic acid presents the highest degree of toxicity, the lowest being shown by dyes with symmetric and asymmetric structures with the following coupling components: 2-amino-8-hydroxynaphthalene-6-sulfonic acid, 1-amino-8-hydroxynaphthalene-3,6-disulfonic acid, 1-(4′-sulfophenyl)-3-methyl-5-pyrazolone, and 2-hydroxy-6-naphthalenesulfonic acid. Full article

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder primarily targeting joints, leading to pain, swelling, and stiffness. RA results from the body’s own immune system attacking its own tissues. Currently, there are various treatments available for RA including disease-modifying antirheumatic drugs (DMARDs) and NSAIDs. Leflunomide (LEF) is a USFDA-approved synthetic DMARD which is being widely prescribed for the management of RA; however, it faces several challenges such as prolonged drug elimination, hepatotoxicity, and others. LEF exerts its therapeutic effects by inhibiting dihydroorotate dehydrogenase (DHODH), thereby suppressing pyrimidine synthesis and modulating immune responses. Emerging nanotechnology-based therapies help in encountering the current challenges faced in LEF delivery to RA patients. This review enlists the LEF’s pharmacokinetics, mechanism of action, and clinical efficacy in RA management. A comparative analysis with methotrexate, biologics, and other targeted therapies, highlighting its role in monotherapy and combination regimens and the safety concerns, including hepatotoxicity, gastrointestinal effects, and teratogenicity, is discussed alongside recommended monitoring strategies. Additionally, emerging trends in novel formulations and drug delivery approaches are explored to enhance efficacy and minimize adverse effects. Overall, LEF remains a perfect remedy for RA patients, specifically individuals contraindicated with drugs like methotrexate. The therapeutic applicability of LEF could be enhanced by developing more customized treatments and advanced drug delivery approaches. Full article

Efficient new methods are needed to support initiatives to reduce, refine, and/or replace toxicity testing in vertebrates. 5-fluorouracil (5FU), hydroxyurea (HU), and ribavirin (RV) are mammalian teratogens. Skeletal, endocrine organ, and cardiac effects are often associated with teratogenesis, and a simple nematode like C. elegans lacks these systems. However, many genetic pathways required for mammalian morphogenesis have at least some conserved elements in this small, invertebrate model. The C. elegans lifecycle is 3 days. The effects of 5FU, HU, and RV on the C. elegans morphology were evaluated on day 4 post-initiation of the feeding after hatching for continuous and 24 h (early-only) developmental exposures. Continuous exposures to 5FU and HU induced increases in the incidences of abnormal gonadal structures that were significantly reduced in early-only exposure groups. The incidence of prolapse increased with continuous 5FU and HU exposures and was further increased in early-only exposure groups. Intestinal prolapse through the vulval muscle in C. elegans may be related to reported 5FU and HU effects on skeletal muscle and the gastrointestinal tract in mammals. Continuous RV exposures induced a phenotype lacking a uterus and gonad arms, as well as vulval anomalies that were largely, but not completely, reversed with early-only exposures, which is consistent with reported reversible reproductive tract anomalies after an RV exposure in mammals. These findings suggest that C. elegans can be used to detect the hazard risk from chemicals that adversely affect conserved pathways involved in organismal morphogenesis, but to determine the fit-for-purpose use of this model in chemical safety evaluations, further studies using larger and more diverse chemical test panels are needed. Full article

Valproic acid (VPA) is a widely prescribed antiepileptic agent whose teratogenic potential has been recognized. In recent years, VPA has been shown to promote neuronal regeneration; however, the exact molecular mechanisms are not fully understood. This study elucidates the pH-dependent pathway through which VPA promotes the differentiation of satellite glial cells (SGCs) into neurons. We observed sustained intracellular pH elevation during the VPA-induced neural differentiation of SGCs, and the modulation of intracellular pH was shown to influence this differentiation process. Then, we found that VPA regulates intracellular pH through NHE1 (sodium–hydrogen exchanger 1), and that the pharmacological inhibition of NHE1 not only attenuated intracellular pH elevation but also substantially impaired VPA-induced neuronal differentiation. Finally, our results showed that the elevated intracellular pH promoted the neuronal differentiation of SGCs by activating β-catenin signaling. These findings provide novel insights into the mechanisms of VPA-induced neurogenesis, advancing our understanding of its pharmacological profile and informing its potential therapeutic application in neuronal regeneration strategies. Full article

Background: Oral isotretinoin is an effective treatment for refractory and moderate acne unresponsive to conventional therapies, considered the most effective option for such cases. Objective: This study aimed to evaluate the knowledge, concerns, and experiences of acne patients undergoing isotretinoin treatment in Qassim, Saudi Arabia, with a focus on commonly reported adverse effects. Methods: A cross-sectional study was conducted from December 2023 to February 2024 using a self-administered questionnaire. This study targeted male and female acne vulgaris patients from the Qassim region attending the outpatient dermatology clinic at King Saud Hospital (KSH). Results: A total of 131 acne patients participated. Of these, 97.7% had heard of isotretinoin, and 92.4% were aware of its side effects. The most common sources of information were colleagues, friends, or family (37.4%), followed by previous use (26%) and healthcare professionals (24%). The most frequently reported side effect was dryness (51.9%), followed by liver function changes (24.4%) and fetal abnormalities (13%). There was a significant association between educational level and knowledge of isotretinoin’s side effects (p = 0.003) and awareness of specific side effects (p < 0.001). Conclusion: Most acne patients had sufficient knowledge of isotretinoin and its adverse effects, with dryness being the most commonly reported side effect. The primary sources of information were non-medical, highlighting the need for health education to ensure informed and safe isotretinoin use. Full article

Hypoglossia and micrognathia are rare congenital malformations. They are most likely to occur after disruption of blastogenesis during embryonic development and formation of the first pharyngeal arch. They may be associated with other malformations such as otocephaly or hypogenesis syndrome of the oromandibular limb. We present the case of a female infant with hypoglossia, micrognathia, and situs inversus as a very rare triadic combination. This clinical presentation does not correspond to the description of existing syndromes. In the available literature, we were able to find only a small number of described cases that are somewhat similar to ours. The etiology of hypoglossia with micrognathia and situs inversus is unknown and has been attributed to both genetic and teratogenic causes. It is also unclear whether the combination of these three malformations can be classified as its own syndrome or not. Here, we present a child born from a pregnancy exposed to the SARS-CoV-2 virus in the first weeks of embryonic development, whose whole genome sequencing confirmed normality, as a contribution to elucidating the etiology of these congenital malformations. The possible influence of the SARS-CoV-2 virus on the occurrence of these anomalies and the exact mechanism of action should be confirmed in subsequent research. Full article

Background/Objectives: Maternal use of medication during pregnancy may have teratogenic effects, as seen with drugs like thalidomide, valproate, and phenytoin. Despite rigorous testing, both new and established drugs still pose a risk of teratogenesis, particularly if the teratogenic effects are probabilistic and not deterministic. Public health organizations maintain registers to centralize and evaluate adverse drug reactions (ADR). However, underreporting in these registries can obscure the signals of drug-related congenital malformations. This study aims to evaluate potential ADR-associated congenital malformations in Denmark over the past decade; Methods: An observational cross-sectional study was conducted using data from the national Danish Medicines Agency’s pharmacovigilance database, which includes all spontaneous ADR reports submitted to the Danish Medicines Agency from 1 July 2013 to 30 June 2023. Maternal antenatal drug use was identified, and reported ADRs were assessed for congenital malformations; Results: We identified reports of potential ADR-related congenital malformations in 75 children, with 92 diagnoses as classified by ICD-10. Eighty-five different drugs from 58 ATC codes were implicated. Only three diagnoses were reported in five or more children. The reports were generally sporadic, with no new signals detected; Conclusions: Public awareness is crucial when novel threats arise from medications, infections, or technologies, as these may pose risks to unborn children. Ongoing monitoring of potential ADR-related congenital malformations remains a critical component of public health. Given the potential underreporting, we encourage a low threshold for reporting ADRs based on suspicion alone, with final causality assessments made by health authorities. Full article

Background and Objectives: The use of antiseizure medications (ASMs) during pregnancy is critical to seizure control in women with epilepsy but raises concerns regarding the use of these drugs and their possible effect on the maternal serum biochemical markers used for second-trimester prenatal screening. The aim of this study was to assess the effect of ASMs on the levels of maternal serum alpha-fetoprotein (AFP), unconjugated estriol (uE3), and human chorionic gonadotropin (hCG) assessed in the serum biomarker analyses part of second-trimester prenatal screening. Materials and Methods: This retrospective cohort study included 43 pregnant women in the ASM-exposed group (levetiracetam, lamotrigine, carbamazepine, or combined therapy) and 43 matched controls without medication use. Groups were matched based on maternal age, gravidity, parity, abortion history, gestational age at testing, body mass index, and smoking status with propensity score matching. Serum AFP, uE3, and hCG levels measured at 15–20 weeks of gestation were compared between groups. The incidence of fetal congenital anomalies or aneuploidies was also compared between groups. Results: Pregnant women in the ASM-exposed group had significantly higher maternal serum AFP (1.34 ± 0.42 vs. 1.01 ± 0.31 MoM; p < 0.001) and uE3 (1.28 ± 0.39 vs. 1.05 ± 0.34 MoM; p = 0.004) than the controls. However, hCG did not differ significantly between the groups (1.07 ± 0.46 vs. 1.01 ± 0.42 MoM; p = 0.523). Regarding the ASM subgroups (levetiracetam, lamotrigine, and carbamazepine), there were no significant differences in the serum biomarkers (p > 0.05). There was no significant difference between the ASM-exposed and control groups in terms of the incidence of congenital anomalies or aneuploidies (2.3% in the ASM-exposed group vs. 2.3% in the control group; p = 1.000). Conclusions: The use of ASMs during pregnancy significantly alters second-trimester maternal serum biochemical markers, including our primary concerns, AFP and uE3, which could cause inaccurate interpretations of second-trimester prenatal screening. Clinicians should carefully consider maternal medication exposure when interpreting these biochemical markers in pregnant women with epilepsy to prevent the misclassification of fetal risks and avoid unnecessary invasive procedures. Full article

Medium chain triglycerides (MCTs) are regarded as an important ingredient for functional foods and nutraceuticals. Cinnamomum camphora seed kernel oil (CCSKO) contains more than 95% medium chain fatty acids (MCFAs), which is a significantly higher level than palm kernel oil (62%) and coconut oil (55%). However, the safety assessment of CCSKO, as the only natural MCT oil rich in capric acid and lauric acid found so far in the world, has not been fully verified. The study aimed to investigate the 90-day sub-chronic oral toxicity and teratogenicity of CCSKO. In the sub-chronic oral toxicity study, no clinically significant adverse events occurred in male or female Sprague–Dawley (SD) rats with CCSKO daily administration for 13 weeks. Moreover, there were no dose–response relationships between CCSKO and body-weight gain, food intake and food utilization in male or female SD rats. No significant differences (p > 0.05) were found in the hematological properties or organ weights between the male and female SD rats. In the teratogenicity test, no toxicological signs were observed in either Wister pregnant rats or fetuses. The no-observed-adverse-effect level of CCSKO was determined to be more than 4 mL/kg body weight. These results suggested that CCSKO may be an excellent edible oil with high oral safety. Full article