Associations of childhood allergies with parental reproductive and allergy history.

PURPOSE: There has been a noted parallel rise in both the use of Assisted Reproductive Technology (ART) to conceive and childhood allergies in the last few decades. The purpose of this study was to investigate the possible association between reproductive and allergy history in parents and allergies in their children. METHODS: This exploratory study used a cross-sectional study design and web-based survey to collect anonymous data on demographics, allergy, and health history from parents and about each of their children under 18 years of age. Children were stratified into two groups by allergy status (yes/no), and associations between each variable and the odds of allergies were tested using univariable and multivariable mixed logistic regression models. RESULTS: Of the 563 children in the study, 237 were reported to have allergies whereas 326 did not. Age, residential community, household income, mode of conception, paternal age at conception, biological parental allergy status, and history of asthma and eczema were significantly associated with allergies in univariable analysis. Multivariable analysis revealed household income ($50 k to $99 k vs ≥ $200 k adj OR = 2.72, 95% CI 1.11, 6.65), biological parental allergies (mother-adj OR 2.74, 95% CI 1.59, 4.72, father-adj OR 2.06, 95% CI 1.24, 3.41) and each additional year of age of children (adj OR 1.17, CI 1.10, 1.24) were significantly associated with odds of allergies in children. CONCLUSION: Although the exploratory nature of this convenience, snowballing sample limited the generalizability of the findings, initial observations warrant further investigation and validation in a larger more diverse population.

Household endotoxin reduction in the Louisa Environmental Intervention Project for rural childhood asthma.

Endotoxin exacerbates asthma. We designed the Louisa Environmental Intervention Project (LEIP) and assessed its effectiveness in reducing household endotoxin and improving asthma symptoms in rural Iowa children. Asthmatic school children (N = 104 from 89 homes) of Louisa and Keokuk counties in Iowa (aged 5-14 years) were recruited and block-randomized to receive extensive (education + professional cleaning) or educational interventions. Environmental sampling collection and respiratory survey administration were done at baseline and during three follow-up visits. Mixed-model analyses were used to assess the effect of the intervention on endotoxin levels and asthma symptoms in the main analysis and of endotoxin reduction on asthma symptoms in exploratory analysis. In the extensive intervention group, dust endotoxin load was significantly reduced in post-intervention visits. The extensive compared with the educational intervention was associated with significantly decreased dust endotoxin load in farm homes and less frequent nighttime asthma symptoms. In exploratory analysis, dust endotoxin load reduction from baseline was associated with lower total asthma symptoms score (Odds ratio: 0.52, 95% confidence interval: 0.29-0.92). In conclusion, the LEIP intervention reduced household dust endotoxin and improved asthma symptoms. However, endotoxin reductions were not sustained post-intervention by residents.

Optimizing Deep Learning for Cardiac MRI Segmentation: The Impact of Automated Slice Range Classification.

RATIONALE AND OBJECTIVES: Cardiac magnetic resonance imaging is crucial for diagnosing cardiovascular diseases, but lengthy postprocessing and manual segmentation can lead to observer bias. Deep learning (DL) has been proposed for automated cardiac segmentation; however, its effectiveness is limited by the slice range selection from base to apex. MATERIALS AND METHODS: In this study, we integrated an automated slice range classification step to identify basal to apical short-axis slices before DL-based segmentation. We employed publicly available Multi-Disease, Multi-View & Multi-Center Right Ventricular Segmentation in Cardiac MRI data set with short-axis cine data from 160 training, 40 validation, and 160 testing cases. Three classification and seven segmentation DL models were studied. The top-performing segmentation model was assessed with and without the classification model. Model validation to compare automated and manual segmentation was performed using Dice score and Hausdorff distance and clinical indices (correlation score and Bland-Altman plots). RESULTS: The combined classification (CBAM-integrated 2D-CNN) and segmentation model (2D-UNet with dilated convolution block) demonstrated superior performance, achieving Dice scores of 0.952 for left ventricle (LV), 0.933 for right ventricle (RV), and 0.875 for myocardium, compared to the stand-alone segmentation model (0.949 for LV, 0.925 for RV, and 0.867 for myocardium). Combined classification and segmentation model showed high correlation (0.92-0.99) with manual segmentation for biventricular volumes, ejection fraction, and myocardial mass. The mean absolute difference (2.8-8.3 mL) for clinical parameters between automated and manual segmentation was within the interobserver variability range, indicating comparable performance to manual annotation. CONCLUSION: Integrating an initial automated slice range classification step into the segmentation process improves the performance of DL-based cardiac chamber segmentation.

Utilizing Artificial Intelligence-Based Deformable Registration for Global and Layer-Specific Cardiac MRI Strain Analysis in Healthy Children and Young Adults.

RATIONALE AND OBJECTIVES: The absence of published reference values for multilayer-specific strain measurement using cardiac magnetic resonance (CMR) in young healthy individuals limits its use. This study aimed to establish normal global and layer-specific strain values in healthy children and young adults using a deformable registration algorithm (DRA). MATERIALS AND METHODS: A retrospective study included 131 healthy children and young adults (62 males and 69 females) with a mean age of 16.6 ± 3.9 years. CMR examinations were conducted using 1.5T scanners, and strain analysis was performed using TrufiStrain research prototype software (Siemens Healthineers, Erlangen, Germany). Global and layer-specific strain parameters were extracted from balanced Steady-state free precession cine images. Statistical analyses were conducted to evaluate the impact of demographic variables on strain measurements. RESULTS: The peak global longitudinal strain (LS) was -16.0 ± 3.0%, peak global radial strain (RS) was 29.9 ± 6.3%, and peak global circumferential strain (CS) was -17.0 ± 1.8%. Global LS differed significantly between males and females. Transmural strain analysis showed a consistent pattern of decreasing LS and CS from endocardium to epicardium, while radial strain increased. Basal-to-apical strain distribution exhibited decreasing LS and increasing CS in both global and layer-specific analysis. CONCLUSION: This study uses DRA to provide reference values for global and layer-specific strain in healthy children and young adults. The study highlights the impact of sex and age on LS and body mass index on RS. These insights are vital for future cardiac assessments in children, particularly for early detection of heart diseases.

What is the angle of a banana? The difficulty in reliable assessment of hypospadias chordee.

INTRODUCTION: The degree of chordee associated with hypospadias impacts operative management. Unfortunately, poor inter-observer reliability in assessing chordee by multiple methods in vitro has been demonstrated. This variability may be related to the fact that chordee is not a discrete angle, but rather an arc-like curvature similar to that of a banana. On an attempt to improve this variability, we assessed the inter-rater reliability of a novel method of chordee measurement and compared it to measurements with a goniometer both in vitro and in vivo. MATERIALS AND METHODS: In vitro assessment of curvature was performed using 5 bananas. In vivo chordee measurement was performed during 43 hypospadias repairs. On in vitro and in vivo cases, chordee was assessed independently by faculty and resident physicians. Angle assessment was performed in a standard manner with a goniometer and with a smartphone app using ruler measurements of the length and width of the arc (Summary Figure). The proximal and distal aspect of the arc to be measured was marked on the bananas, whereas the penile measurements were taken from the penoscrotal to the sub-coronal junctions. RESULTS: In vitro banana assessment demonstrated strong intra- and inter-rater reliability for length (0.89 and 0.88, respectively) and width measurements (0.97 and 0.96). The calculated angle demonstrated an intra- and inter-rater reliability of 0.67 and 0.67. The banana goniometer/protractor measurements were weak with an intra-rater and inter-rater reliability of 0.33 and 0.21. With hypospadias chordee, the inter-rater reliability was strong for length and width measurements (0.95 and 0.94) and 0.48 for calculated angle. The inter-rater reliability of the goniometer angle was 0.96. Further assessment of inter-rater goniometer reliability was performed relative to degree of chordee as characterized by faculty. The inter-rater reliability for ≤15°, 16-30, and ≥30° was 0.68 (n = 20), 0.34 (n = 14), and 0.90 (n = 9), respectively. When the goniometer angle was classified as ≤15, 16-30, or ≥30° by one physician, it was classified outside of this range by the other physician 23%, 47%, and 25% of the time, respectively. DISCUSSION: Our data demonstrate significant limitations of the goniometer for assessing chordee in vitro and in vivo. We were unable to demonstrate significant improvement in chordee assessment using arc length and width measurements to calculate radians. CONCLUSIONS: Reliable and precise techniques for measuring hypospadias chordee remain elusive and draw into question the validity and usability of management algorithms employing discrete values.

Cerium Oxide Enhances the Toxicity of Zinc Oxide Nanoparticles in Human Lung Epithelial Cell Cultures.

Recently, many approaches have been developed to improve the performance of nanomaterials. Combining more than one nanomaterial is one such approach that achieves superior results. However, during the fabrication of nanomaterials or formulation of end products, materials can be released into the ambient air and be inhaled by workers. The adverse health outcomes of inhaling such compounds are unknown. In this study, we examined such effects in combining two of the most utilized nanomaterials in several industrial sectors: zinc oxide (ZnO) and cerium oxide (CeO2). These materials can be found together in sunscreens, polyvinyl alcohol (PVA) films, and construction products. The aim of this study was to assess the adverse biological outcomes of CeO2-ZnO nano-mixtures in human lung epithelial cells. A549 human lung epithelial cells were treated with increasing concentrations of ZnO or CeO2 NPs alone, or as a mixture of both, under submerged conditions for 24 h. After treatment, cell viability, reactive oxygen species (ROS) formation, cell membrane integrity, and cytokine production were examined. ZnO NPs showed a dose-dependent trend for all endpoints. CeO2 NPs did not exhibit any toxic effect in any individual concentrations. When higher doses of ZnO were combined with increasing doses of CeO2, loss of cell viability and an elevation in cell membrane leakage were observed. Interleukin 8 (IL-8) and ROS generation were higher when ZnO NPs were combined with CeO2 NPs, compared to cells that were treated with ZnO alone. The release of monocyte chemoattractant protein-1 (MCP-1) was reduced in the cells that were treated with higher doses of ZnO and CeO2. Thus, the presence of CeO2 enhanced the toxicity of ZnO in A549 cells at non-toxic levels of CeO2. This suggests an additive toxicity of these two nanomaterials.

Factors contributing to missed opportunities for human papillomavirus vaccination among adolescents, ages 11 to 13, in Iowa.

Introduction: Rates of human papillomavirus (HPV) vaccination remain low and missed opportunities for HPV vaccination are widespread. Researchers have identified factors related to HPV vaccination, but less is known about missed opportunities. Methods: We used medical claims data from a large Midwestern insurance provider to explore relationships between adolescent and provider characteristics and missed opportunities for HPV vaccination. We stratified models by initiation status with adolescents who had received one or more HPV vaccinations in one group (n = 6,123) and adolescents with no record of an HPV vaccination in the other (n = 8,107). Results: There were significant differences in comparisons of all variables between initiators and non-initiators. Notably, non-initiators had lower rates of vaccination for HPV and other adolescent vaccinations, and fewer well-child visits. For all adolescents, birth year, having other recommended vaccines, and number of well-child visits were significantly associated with missed opportunities. Additionally, among initiators, pediatrician as a primary care provider and being in a rural area were significantly associated. Discussion: Overall, adolescents with greater healthcare utilization had more missed opportunities, indicating that, despite increased numbers of visits, providers are not taking advantage of these opportunities to vaccinate. Future research should prioritize developing a deeper understanding of why these missed opportunities are occurring and implementing new and existing strategies to prevent them. Reducing missed opportunities will help to prevent future HPV-related cancers and the significant morbidity and mortality that they can cause.

Evaluation of the Limulus amebocyte lysate and recombinant factor C assays for assessment of airborne endotoxin.

As a potent inflammatory agent, endotoxin is a key analyte of interest for studies of lung ailments in domestic environments and occupational settings with organic dust. A relatively unexplored advance in endotoxin exposure assessment is the use of recombinant factor C (rFC) from the Limulus pathway in a fluorometric assay. In this study, we compared airborne endotoxin concentrations in laboratory- and field-collected parallel air samples using the kinetic Limulus amebocyte lysate (LAL) assay and the rFC assay. Air sampling was performed using paired Institute of Occupational Medicine (IOM) samplers, Button samplers, closed-face cassettes, and cyclone samplers. Field sampling was performed in 10 livestock production facilities, including those housing swine, chicken, turkey, dairy cows, cattle, and horses. Laboratory sampling was performed in exposure chambers using resuspended airborne dust collected in five livestock facilities. Paired samples were extracted in pyrogen-free water with 0.05% Tween 20 and analyzed using LAL and rFC assays. In 402 field sample pairs there was excellent agreement between endotoxin concentrations determined by LAL and rFC (r = 0.93; P < 0.0001). In 510 laboratory sample pairs there was also excellent agreement between the two assays (r = 0.86; P < 0.0001). Correlations for subgroups of facility or dust type ranged from 0.65 to 0.96. Mixed-model analysis of variance (ANOVA) for the field studies showed significant interactions of facility-sampler and facility-assay. rFC/LAL ratios of the geometric means were 0.9 to 1.14 for the samplers (not significantly different from 1.0). The data from this study demonstrate that the LAL assay and the rFC assay return similar estimates of exposure in livestock facilities. Both methods provided suitable lower limits of detection such that all but 19 of 1,824 samples were quantifiable.

Modulation of reactive oxygen species by Rac1 or catalase prevents asbestos-induced pulmonary fibrosis.

The release of reactive oxygen species (ROS) and cytokines by alveolar macrophages has been demonstrated in asbestos-induced pulmonary fibrosis, but the mechanism linking alveolar macrophages to the pathogenesis is not known. The GTPase Rac1 is a second messenger that plays an important role in host defense. In this study, we demonstrate that Rac1 null mice are protected from asbestos-induced pulmonary fibrosis, as determined by histological and biochemical analysis. We hypothesized that Rac1 induced pulmonary fibrosis via generation of ROS. Asbestos increased TNF-alpha and ROS in a Rac1-dependent manner. TNF-alpha was elevated only 1 day after exposure, whereas ROS generation progressively increased in bronchoalveolar lavage cells obtained from wild-type (WT) mice. To determine whether ROS generation contributed to pulmonary fibrosis, we overexpressed catalase in WT monocytes and observed a decrease in ROS generation in vitro. More importantly, administration of catalase to WT mice attenuated the development of fibrosis in vivo. For the first time, these results demonstrate that Rac1 plays a crucial role in asbestos-induced pulmonary fibrosis. Moreover, it suggests that a simple intervention may be useful to prevent progression of the disease.

Maximum Pairwise Pseudo-Likelihood Estimation of the Covariance Matrix from Left-Censored Data.

Toxicological studies often depend on laboratory assays that have thresholds below which environmental pollutants cannot be measured with accuracy. Exposure levels below this limit of detection may well be toxic and hence it is vital to use data analytic methods that handle such left-censored data with as little estimation bias as possible. In an on-going study for which our methodology is developed, levels of residential exposure to polychlorinated biphenyls (PCBs) and the interrelationships of their subtypes (congeners) are characterized. In any given sample many of the congeners may fall below the detection limit. The main problem tackled in this paper is estimation of mean exposure levels and corresponding covariance and correlation matrices for a large number of potentially left-censored measures that have very low bias and are computationally feasible. The proposed methods are likelihood based, using marginal likelihoods for means and variances and pairwise pseudo-likelihoods for correlations and covariances. In the simple bi- variate case, head-to-head comparisons show the proposed methods to be computationally more stable than ordinary maximum likelihood estimates (MLEs) and still maintain comparable bias. When the number of variables is much larger than 2, the proposed methods are far more computationally feasible than MLE. Furthermore, they exhibit much less bias when compared to popular imputation procedures. Analysis of the PCB data uncovered interesting correlational structures.