BackgroundThe pervasive nature of plastics has raised concerns about the impact of continuous exposure to plastic additives on human health. Of particular concern is the use of phthalates in the production of flexible polyvinyl chloride (PVC) products. Di-2-ethylhexyl-phthalate (DEHP) is a commonly used phthalate ester plasticizer that imparts flexibility and elasticity to PVC products. Recent epidemiological studies have reported correlations between urinary phthalate concentrations and cardiovascular disease, including an increased risk of high blood pressure and coronary risk. Yet, there is little direct evidence linking phthalate exposure to adverse effects in human cells, including cardiomyocytes.Methods and ResultsThe effect of DEHP on calcium handling was examined using monolayers of gCAMP3 human embryonic stem cell-derived cardiomyocytes, which contain an endogenous calcium sensor. Cardiomyocytes were exposed to DEHP (5 – 50 μg/mL), and calcium transients were recorded using a Zeiss confocal imaging system. DEHP exposure (24 – 72 hr) had a negative chronotropic and inotropic effect on cardiomyocytes, increased the minimum threshold voltage required for external pacing, and modified connexin-43 expression. Application of Wy-14,643 (100 μM), an agonist for the peroxisome proliferator-activated receptor alpha, did not replicate DEHP’s effects on calcium transient morphology or spontaneous beating rate.ConclusionsPhthalates can affect the normal physiology of human cardiomyocytes, including DEHP elicited perturbations in cardiac calcium handling and intercellular connectivity. Our findings call for additional studies to clarify the extent by which phthalate exposure can alter cardiac function, particularly in vulnerable patient populations who are at risk for high phthalate exposure.

Analysis of cranial nerve systems, such as the anterior visual pathway (AVP), from MRI sequences is challenging due to their thin long architecture, structural variations along the path, and low contrast with adjacent anatomic structures. Segmentation of a pathologic AVP (e.g., with low-grade gliomas) poses additional challenges. In this work, we propose a fully automated partitioned shape model segmentation mechanism for AVP steered by multiple MRI sequences and deep learning features. Employing deep learning feature representation, this framework presents a joint partitioned statistical shape model able to deal with healthy and pathological AVP. The deep learning assistance is particularly useful in the poor contrast regions, such as optic tracts and pathological areas. Our main contributions are: 1) a fast and robust shape localization method using conditional space deep learning, 2) a volumetric multiscale curvelet transform-based intensity normalization method for robust statistical model, and 3) optimally partitioned statistical shape and appearance models based on regional shape variations for greater local flexibility. Our method was evaluated on MRI sequences obtained from 165 pediatric subjects. A mean Dice similarity coefficient of 0.779 was obtained for the segmentation of the entire AVP (optic nerve only =0.791 ) using the leave-one-out validation. Results demonstrated that the proposed localized shape and sparse appearance-based learning approach significantly outperforms current state-of-the-art segmentation approaches and is as robust as the manual segmentation.

Greater OPG and AVP volume predicts axonal degeneration, a biomarker of vision loss, in children with NF1-OPGs. MRI volumetric measures may help stratify the risk of visual loss from NF1-OPGs.

Quantitative reference values for AVP enlargement will enhance the development of objective diagnostic criteria for OPGs secondary to NF1.

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Biomonitoring studies indicate that 90% of the population is routinely exposed to Bisphenol‐A (BPA), a compound commonly found in household plastics. Environmental exposure varies between 1– 100 nM, while clinical and industrial exposure can reach 10 uM. Epidemiological studies have shown an association between increased BPA exposure and cardiovascular diseases. We aimed to test the direct effects of BPA on cardiac function using a Langendorff‐perfusion model. Excised female rat hearts were treated with 1 nM‐10 uM BPA and the resulting effects on cardiac mechanical function and calcium handling were monitored. For calcium imaging, excised hearts were treated with Blebbistatin to arrest mechanical function, and then stained with Rhod‐2, a calcium indicator dye. Epicardial calcium transients were recorded using an Andor CCD camera equipped with wavelength specific filters (570+/‐ 30 nm), and an LED spotlight (535 nm) was used for dye excitation. Calcium transients were initiated at various pacing frequencies (5Hz, 6.6Hz, and 9Hz). To assess the effect of BPA on the mechanical function of the heart, a latex balloon was inserted into the left‐ventricle to quantitate left‐ventricular developed pressure (LVDP) and maximum contractility. At high pacing frequencies, BPA decreased LVDP by 16% at 1 nM, 24% at 100nM and 36% at 10 uM, while the maximum contractility decreased by 23% at 100 nM and 33% at 10 uM. We conclude that alterations to mechanical function and calcium handling are a sensitive parameter for assessing BPA cardiac toxicity.