Acrylamide, an air pollutant, enhances allergen-induced eosinophilic lung inflammation via group 2 innate lymphoid cells.

Air pollution significantly impacts the aggravation of asthma. Exposure to acrylamide, a volatile organic compound in tobacco smoke, is associated with elevated risks of allergy-related outcomes among active smokers. As group 2 innate lymphoid cells (ILC2s) can act as an environmental sensor and significantly contribute to protease allergen-induced lung inflammation, we aimed to elucidate the causal relationship and how inhaled acrylamide worsens allergic lung inflammation via ILC2s. Intranasal acrylamide exposure at nanomolar levels significantly enhanced allergen-induced or recombinant mouse interleukin-33-induced lung inflammation in C57BL/6 mice or Rag1-/- mice, respectively. The cardinal features of lung inflammation included accumulated infiltration of ILC2s and eosinophils. Transcriptomic analysis revealed a gene expression pattern associated with proliferation-related pathways in acrylamide-treated ILC2s. Western blotting revealed significantly higher expression of Ras and phospho-Erk in acrylamide-treated ILC2s than the control, suggesting Ras-Erk signaling pathway involvement. Ex vivo and in vitro analysis showed that acrylamide treatment mainly increased Ki-67+ ILC2s and the cell number of ILC2s whereas PD98059, a highly selective Erk inhibitor, effectively counteracted the acrylamide effect. Intratracheal administration of acrylamide-treated ILC2s significantly enhanced eosinophil infiltration in Rag1-/- mice. This study suggests that airborne acrylamide may enhance the severity of allergen-induced airway eosinophilic inflammation, partly via altering ILC2 proliferative activity.

Maternal di-(2-ethylhexyl) phthalate exposure elicits offspring IFN-λ upregulation: Insights from birth cohort, murine model, and in vitro mechanistic analysis.

Maternal exposure to di-(2-ethylhexyl)-phthalate (DEHP), an environmental endocrine disruptor, may lead to developmental immunotoxicity in offspring. The causal relationship and underlying mechanism require further study. A subset of Taiwan Maternal and Infant Cohort Study data (n = 283) was analyzed and found a significant association between urinary DEHP metabolite levels from the third trimester of pregnancy and plasma levels of IL-28A and IL-29, named IFNλs, in cord blood. A trans-maternal murine model mimicking human DEHP exposure way showed that bone marrow-derived dendritic cells from maternal DEHP-exposed F1 offspring secreted higher IL-28A levels than control cells, indicating a potential causal relationship. Human bronchial epithelial cell lines treated with DEHP or its primary metabolite, mono-(2-ethyl-5-hexyl) phthalate (MEHP), expressed significantly higher levels of IFNλs mRNA or protein than controls. MEHP's effect on IFNλs expression was blocked by peroxisome proliferator-activated receptor α (PPARα) and PPARγ antagonists, and inhibited by a histone acetyltransferase inhibitor or a histone methyltransferase inhibitor. Chromatin immunoprecipitation assay showed that MEHP treatment promoted histone modifications at H3 and H4 proteins at the promoter regions of Il28a and Il29 genes. These results suggest maternal DEHP exposure could result in high IFNλ expression in offspring, and the health risk of early-life exposure requires further investigation.

Di-(2-ethylhexyl) Phthalate Promotes Allergic Lung Inflammation by Modulating CD8α+ Dendritic Cell Differentiation via Metabolite MEHP-PPARγ Axis.

Di-(2-ethylhexyl) phthalate (DEHP), a common plasticizer, is a ubiquitous environmental pollutant that can disrupt endocrine function. Epidemiological studies suggest that chronic exposure to DEHP in the environment is associated with the prevalence of childhood allergic diseases; however, the underlying causal relationship and immunological mechanism remain unclear. This study explored the immunomodulatory effect of DEHP on allergic lung inflammation, while particularly focusing on the impact of DEHP and its metabolite on dendritic cell differentiation and activity of peroxisome proliferator-activated receptor gamma (PPARγ). The results showed that exposure to DEHP at a human tolerable daily intake dose exacerbated allergic lung inflammation in mice. Ex vivo flow cytometric analysis revealed that DEHP-exposed mice displayed a significantly decreased number of CD8α+ dendritic cells (DCs) in spleens and DC progenitors in the bone marrow, as well as, less interleukin-12 production in splenic DCs and increased T helper 2 polarization. Pharmacological experiments showed that mono-(2-ethylhexyl) phthalate (MEHP), the main metabolite of DEHP, significantly hampered the differentiation of CD8α+ DCs from Fms-like tyrosine kinase 3 ligand-differentiated bone marrow culture, by modulating PPARγ activity. These results suggested that chronic exposure to DEHP at environmentally relevant levels, promotes allergic lung inflammation, at least in part, by altering DC differentiation through the MEHP-PPARγ axis. This study has crucial implications for the interaction(s) between environmental pollutants and innate immunity, with respect to the development of allergic asthma.

Accurate Image-guided (Re)Placement of NIRS Probes.

BACKGROUND AND OBJECTIVE: Functional near-infrared spectroscopy (fNIRS) has become an attractive choice to neuroscience because of its high temporal resolution, ease of use, non-invasiveness, and affordability. With the advent of wearable fNIRS technology, on-the-spot studies of brain function have become viable. However, the lack of within-subject reproducibility is one of the barriers to the full acceptability of fNIRS. To support the validation of the claim that within-subject reproducibility of fNIRS could benefit from accurate anatomical information, we present in this paper a method to develop an image-based system that improves the placement of the sensors on the scalp at interactive rates. METHODS: The proposed solution consists of an electromagnetic digitizer and an interactive visualization system that allows monitoring the movements of the digitizer on a real head with respect to the underlying cerebral cortical structures. GPU-based volume raycasting rendering is applied to unveil these structures from the corresponding magnetic resonance imaging volume. Scalp and cortical surface are estimated from the scanned volume to improve depth perception. An alignment algorithm between the real and scanned heads is devised to visually feedback the position of the stylus of the digitizer. Off-screen rendering of the depthmaps of the visible surfaces makes spatial positioning of a 2D interaction pointer possible. RESULTS: We evaluated the alignment accuracy using four to eight anatomical landmarks and found seven to be a good compromise between precision and efficiency. Next, we evaluated reproducibility in positioning five arbitrarily chosen points on three volunteers by four operators over five sessions. In every session, seven anatomical landmarks were applied in the alignment of the real and the scanned head. For the same volunteer, one-way analysis of variance (ANOVA) revealed no significant differences within the five points digitized by the same operator over five sessions (α = 0.05). In addition, preliminary study of motor cortex activation by right-hand finger tapping showed the potential of our approach to increase functional fNIRS reproducibility. CONCLUSIONS: Results of experiments suggest that the enhancement of the visualization of the location of the probes on the scalp, relative to the underlying cortical structures, improves reproducibility of fNIRS measurements. As further work, we plan to study the fNIRS reproducibility in other cortical regions and in clinical settings using the proposed system.

Integration of Spatial Information Increases Reproducibility in Functional Near-Infrared Spectroscopy.

As functional near-infrared spectroscopy (fNIRS) is developed as a neuroimaging technique and becomes an option to study a variety of populations and tasks, the reproducibility of the fNIRS signal is still subject of debate. By performing test-retest protocols over different functional tasks, several studies agree that the fNIRS signal is reproducible over group analysis, but the inter-subject and within-subject reproducibility is poor. The high variability at the first statistical level is often attributed to global systemic physiology. In the present work, we revisited the reproducibility of the fNIRS signal during a finger-tapping task across multiple sessions on the same and different days. We expanded on previous studies by hypothesizing that the lack of spatial information of the optodes contributes to the low reproducibility in fNIRS, and we incorporated a real-time neuronavigation protocol to provide accurate cortical localization of the optodes. Our proposed approach was validated in 10 healthy volunteers, and our results suggest that the addition of neuronavigation can increase the within-subject reproducibility of the fNIRS data, particularly in the region of interest. Unlike traditional approaches to positioning the optodes, in which low intra-subject reproducibility has been found, we were able to obtain consistent and robust activation of the contralateral primary motor cortex at the intra-subject level using a neuronavigation protocol. Overall, our findings support the hypothesis that at least part of the variability in fNIRS cannot be only attributed to global systemic physiology. The use of neuronavigation to guide probe positioning, as proposed in this work, has impacts to longitudinal protocols performed with fNIRS.

Interactive patient-customized curvilinear reformatting for improving neurosurgical planning.

PURPOSE: Visualizing a brain in its native space plays an essential role during neurosurgical planning because it allows the superficial cerebral veins and surrounding regions to be preserved. This paper describes the use of a visualization tool in which single gadolinium contrast-enhanced T1-weighted magnetic resonance imaging was applied in nondefective and nonresective skulls to promote visualization of important structures. METHODS: A curvilinear reformatting tool was applied on the supratentorial compartment to peel the tissues to the depth of the dura mater and thereby revealing cortical and vascular spatial relationships. The major advantage of our proposed tool is that it does not require coregistration of anatomical and vascular volumes. RESULTS: The reliability of this technique was supported by comparisons between preoperative images and digital photographs of the brain cortical surface obtained after the dura mater was removed in 20 patients who underwent surgery in the Clinics Hospital of the University of Campinas from January 2017 to April 2018. CONCLUSION: Single fat-suppressed GAD contrast-enhanced T1-weighted magnetic resonance scans provide accurate preoperative 3D views of cortical and vascular relationships similar to neurosurgeons' intraoperative views. In developing countries with limited access to state-of-the-art health technologies, this imaging approach may improve the safety of complex neurosurgeries.

Toward a Multimodal Diagnostic Exploratory Visualization of Focal Cortical Dysplasia.

Focal cortical dysplasia (FCD) is a malformation of cortical development and a common cause of pharmacoresistant epilepsy. Resective surgery of clear-cut lesions may be curative. However, the localization of the seizure focus and the evaluation of its spatial extent can be challenging in many situations. For concordance assessment, medical studies show the relevance of accurate correlation of multisource imaging sequences. to improve the sensitivity and specificity of the evaluation. In this paper, we share the process we went through to reach our simple, but effective, solution for integrating multi-volume rendering into an exploratory visualization environment for the diagnosis of FCD. We focus on fetching of multiple data assigned to a sample when they are rendered. Knowing that the major diagnostic role of multiple volumes is to complement information, we demonstrate that appropriate geometric transformations in the texture space are sufficient for accomplishing this task. This allows us to fully implement our proposal in the OpenGL rendering pipeline and to easily integrate it into the existing visual diagnostic application. Both time performance and the visual quality of our proposal were evaluated with a set of clinical data volumes for assessing the potential practical impact of our solution in routine diagnostic use.