Intrauterine smoke (IUS) exposure during early childhood has been associated with a number of negative health consequences, including reduced lung function and asthma susceptibility. The biological mechanisms underlying these associations have not been established. MicroRNAs regulate the expression of numerous genes involved in lung development. Thus, investigation of the impact of IUS on miRNA expression during human lung development may elucidate the impact of IUS on post-natal respiratory outcomes. We sought to investigate the effect of IUS exposure on miRNA expression during early lung development. We hypothesized that miRNA–mRNA networks are dysregulated by IUS during human lung development and that these miRNAs may be associated with future risk of asthma and allergy. Human fetal lung samples from a prenatal tissue retrieval program were tested for differential miRNA expression with IUS exposure (measured using placental cotinine concentration). RNA was extracted and miRNA-sequencing was performed. We performed differential expression using IUS exposure, with covariate adjustment. We also considered the above model with an additional sex-by-IUS interaction term, allowing IUS effects to differ by male and female samples. Using paired gene expression profiles, we created sex-stratified miRNA–mRNA correlation networks predictive of IUS using DIABLO. We additionally evaluated whether miRNAs were associated with asthma and allergy outcomes in a cohort of childhood asthma. We profiled pseudoglandular lung miRNA in n = 298 samples, 139 (47%) of which had evidence of IUS exposure. Of 515 miRNAs, 25 were significantly associated with intrauterine smoke exposure (q-value < 0.10). The IUS associated miRNAs were correlated with well-known asthma genes (e.g., ORM1-Like Protein 3, ORDML3) and enriched in disease-relevant pathways (oxidative stress). Eleven IUS-miRNAs were also correlated with clinical measures (e.g., Immunoglobulin E andlungfunction) in children with asthma, further supporting their likely disease relevance. Lastly, we found substantial differences in IUS effects by sex, finding 95 significant IUS-miRNAs in male samples, but only four miRNAs in female samples. The miRNA–mRNA correlation networks were predictive of IUS (AUC = 0.78 in males and 0.86 in females) and suggested that IUS-miRNAs are involved in regulation of disease-relevant genes (e.g., A disintegrin and metalloproteinase domain 19 (ADAM19), LBH regulator of WNT signaling (LBH)) and sex hormone signaling (Coactivator associated methyltransferase 1(CARM1)). Our study demonstrated differential expression of miRNAs by IUS during early prenatal human lung development, which may be modified by sex. Based on their gene targets and correlation to clinical asthma and atopy outcomes, these IUS-miRNAs may be relevant for subsequent allergy and asthma risk. Our study provides insight into the impact of IUS in human fetal lung transcriptional networks and on the developmental origins of asthma and allergic disorders.
Background/Objectives: Pediatric critical illness constitutes a highly stressful event not only for the critically ill child but also for the broader family unit. Recognizing and addressing these family-level effects is essential to optimizing outcomes for PICU survivors. Methods: This prospective observational cohort study examined anxiety and depression in parents of pediatric ICU patients prior to PICU discharge using the Hospital Anxiety and Depression (HADS) scale, and again after 30 days. At follow-up, parents were also screened for post-traumatic stress symptoms (PTSS) using the Impact of Events (IES) scale. Parent demographics and characteristics of the child’s hospitalization were collected. Results: 235 parents enrolled and completed a HADS; 126 parents (54%) subsequently completed a follow-up HADS and IES. 50% of parents screened positive for anxiety and/or depression prior to discharge; 44% of parents demonstrated anxiety, depression, and/or PTSS on follow-up screening. A positive HADS prior to discharge was the only independent predictor of persistent psychological symptoms. Conclusions: Parental psychological distress is both common and persistent following a child’s PICU admission. Screening at discharge is a feasible method to identify families at the highest risk for enduring anxiety, depression, and post-traumatic stress symptoms.
Formal medical toxicology training is limited in many resource-constrained regions, including India, where poisonings and envenomations are highly prevalent. There is an urgent need for accessible toxicology education for healthcare providers in these settings. This study evaluates a novel augmented reality-based observed simulation model to remotely teach medical toxicology concepts to physicians-in-training in India. A toxicology topic relevant to India was selected, and key learning objectives defined. An augmented reality-based module was developed involving a clinical-case simulation with overlaid visuals. The trainer in the United States, streamed the session via an augmented reality headset to learners in India using a virtual communication platform. A user experience survey and pre-/post-tests were conducted immediately before and after the educational session, with knowledge gain analyzed using a paired t-test (P <0.05). One hundred and twenty-four participants attended, comprising third- and fourth-year medical students and interns. The mean post-test score improved significantly from 11.10 (±2.81) to 16.80 (±2.37; maximum score: 20), with a mean increase of 5.70 (±2.91, P <0.001). Qualitative feedback supported augmented reality and simulation as effective remote teaching tools. This study demonstrates the feasibility of using an augmented reality and simulation-based remote model to teach medical toxicology. A statistically significant improvement in test scores indicated short-term knowledge gain. Important limitations included the absence of delayed post-testing to assess retention, lack of a comparator group taught using traditional instructional methods, and no use of validated tools to measure immersion and motivation. Augmented reality and simulation-based remote teaching models can serve as effective, immersive, and interactive tools where in-person training is constrained. They offer a much-needed opportunity to link institutions with established medical toxicology programs to physicians in countries lacking formal training, helping bridge critical global education gaps.