Mariko Sato

To define the intrahepatic distribution of iodized poppyseed oil and its effect on the liver, hepatic artery embolization (HAE) was performed in five mice, 12 rats, four rabbits, and 21 pigs with the iodized oil alone or in combination with gelatin sponge powder (GSPow) in three rats or gelatin sponge particles (GSPs) in nine pigs. All mice, rats, and rabbits underwent radiography of the upper abdomen and in vivo microscopy of the hepatic periphery during and immediately after injection and 1, 4, and 24 hours later. All pigs underwent angiography before and after HAE as well as measurement of portal venous pressure before HAE and 15, 30, 45, and 60 minutes and 4 weeks after HAE. Follow-up radiographs were obtained in 18 pigs. HAE performed with the iodized oil only was well tolerated by the liver, even when high doses were used, likely because of continuous flushing of the sinusoids by high blood flow from peripheral arterioles. When HAE was performed with the iodized oil and GSPow, this blood flow ceased and necrosis developed. The degree of necrosis after HAE with the iodized oil in combination with GSPs was directly associated with the dose of iodized oil. HAE performed with GSPs only did not cause damage.

Epidermal lipids are important for skin homeostasis. However, the entire picture of the roles of lipids, particularly nonceramide lipid species, in epidermal biology still remains obscure. Here, we report that PLA2G2F, a functionally orphan-secreted phospholipase A2 expressed in the suprabasal epidermis, regulates skin homeostasis and hyperplasic disorders. Pla2g2f(-/-) mice had a fragile stratum corneum and were strikingly protected from psoriasis, contact dermatitis, and skin cancer. Conversely, Pla2g2f-overexpressing transgenic mice displayed psoriasis-like epidermal hyperplasia. Primary keratinocytes from Pla2g2f(-) (/-) mice showed defective differentiation and activation. PLA2G2F was induced by calcium or IL-22 in keratinocytes and preferentially hydrolyzed ethanolamine plasmalogen-bearing docosahexaenoic acid secreted from keratinocytes to give rise to unique bioactive lipids (i.e., protectin D1 and 9S-hydroxyoctadecadienoic acid) that were distinct from canonical arachidonate metabolites (prostaglandins and leukotrienes). Ethanolamine lysoplasmalogen, a PLA2G2F-derived marker product, rescued defective activation of Pla2g2f(-/-) keratinocytes both in vitro and in vivo. Our results highlight PLA2G2F as a previously unrecognized regulator of skin pathophysiology and point to this enzyme as a novel drug target for epidermal-hyperplasic diseases.

<h3>Objective</h3> To evaluate lesion location after pediatric cerebellar tumor resection in relation to the development of severe cognitive and affective disturbances, or cerebellar cognitive affective syndrome (CCAS). <h3>Methods</h3> The postsurgical lesion location of 195 pediatric patients with cerebellar tumors was mapped onto a template brain. Individuals with CCAS were matched to 2 participants without CCAS by sex, age, and lesion volume. Lesion analyses included both a hypothesis-driven evaluation of the cerebellar outflow pathway (deep nuclei and superior cerebellar peduncles) and data-driven multivariate lesion symptom mapping. Lesion-associated networks were evaluated by comparing connectivity patterns between the lesion location of cases with and those without CCAS with resting-state functional connectivity MRI data from large normative adult and pediatric cohorts. <h3>Results</h3> CCAS was present in 48 of 195 participants (24.6%) and was strongly associated with cerebellar outflow tract lesions (<i>p</i> &lt; 0.0001). Lesion symptom mapping also highlighted the cerebellar outflow pathway, with peak findings in the fastigial nuclei extending into the inferior vermis. Lesion network mapping revealed that the cerebellar region most associated with CCAS was functionally connected to the thalamic mediodorsal nucleus, among other sites, and that higher connectivity between lesion location and the mediodorsal nucleus predicts CCAS occurrence (<i>p</i> &lt; 0.01). A secondary analysis of 27 participants with mutism revealed similar localization of lesions and lesion-associated networks. <h3>Conclusion</h3> Lesions of the cerebellar outflow pathway and inferior vermis are associated with major cognitive and affective disturbances after pediatric cerebellar tumor resection, and disrupted communication between the cerebellum and the thalamic mediodorsal nucleus may be important.