Classifications of seizures and epilepsies, where are we? - A brief historical review and update.

In March 2017, the International League Against Epilepsy (ILAE) announced their new classifications of seizures and epilepsies. Development of these classification systems led by the ILAE is a long and complicated process. Outsiders may find it difficult to understand the arguments behind. We summarize the major developmental milestones of the ILAE classification schemata. An update of the latest classification is also included. It is hope that this review can serve as an outline in learning the taxonomy in epileptology.

Correlation of PD-L1 Expression of Tumor Cells with Survival Outcomes after Radical Intensity-Modulated Radiation Therapy for Non-Metastatic Nasopharyngeal Carcinoma.

PURPOSE: We investigated if programmed death-ligand 1 (PD-L1) expression levels were prognostic of survival outcomes after intensity-modulated radiation therapy (IMRT) for non-metastatic nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: 104 patients with non-metastatic NPC treated with radical IMRT were investigated for their PD-L1 expression by immunohistochemistry (IHC) which were correlated with survival endpoints including locoregional failure-free survival (LRFFS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and overall survival (OS). RESULTS: After a median follow-up of 7.6 years, 21 (20.2%), 19 (18.3%) and 31 (29.8%) patients suffered from locoregional failure, distant metastases and overall disease progression, respectively, and 31 (29.8%) patients died. Patients whose tumors had PD-L1 IHC 2+ (moderate to strong membrane staining in ≥ 25% of tumor cells) enjoyed longer LRFFS (5-year 100% vs. 74.4%, Hazard ratio [HR], 0.159, 95% confidence interval [CI], 0.021-0.988; P = 0.042) and marginally longer PFS (5-year 95.0% vs. 65.2%, HR, 0.351, 95% CI, 0.08-0.999, P = 0.067) compared to those whose tumors had PD-L1 IHC 0 (minimal membrane staining with PD-L1 in < 5% tumor cells or no staining with PD-L1) or 1+ (minimal to moderate membrane staining with PD-L1 in between 5-24% tumor cells). PD-L1 IHC 2+ was independently prognostic of both LRFFS (P = 0.014) and PFS (P = 0.045) in multivariable analyses. Only induction chemotherapy followed by concurrent chemoradiation was prognostic of DMFS (P = 0.003) and no prognostic factor for OS was identified. CONCLUSION: PD-L1 expression levels correlated with LRRFS and PFS in non-metastatic NPC treated with radical IMRT. It may play a role in radiosensitivity for NPC, which should be further confirmed in prospective studies using immunotherapy together with IMRT.

Quantitative image analysis of cell behavior and molecular dynamics during tissue morphogenesis.

The cell behaviors that drive tissue morphogenesis, such as division, migration, or death, are regulated at the molecular scale. Understanding how molecular events determine cell behavior requires simultaneous tracking and measurement of molecular and cellular dynamics. To this end, we have developed SIESTA, an integrated tool for Scientific ImagE SegmenTation and Analysis that enables quantification of cell behavior and molecular events from image data. Here we use SIESTA to show how to automatically delineate cells in images (segmentation) using the watershed algorithm, a region-growing method for boundary detection. For images in which automated segmentation is not possible due to low or inappropriate contrast, we use a minimal path search algorithm to semiautomatically delineate the cells. We use the segmentation results to quantify cellular morphology and molecular dynamics in different subcellular compartments, and demonstrate the whole process by analyzing cell behavior and the dynamics of the motor protein non-muscle myosin II during axis elongation in a Drosophila embryo. Finally, we show how image analysis can be used to quantify molecular asymmetries that orient cell behavior, and demonstrate this point by measuring planar cell polarity in Drosophila embryos. We describe all methods in detail to allow their implementation and application using other software packages. The use of (semi) automated quantitative imaging enables the analysis of a large number of samples, thus providing the statistical power necessary to detect subtle molecular differences that may result in differences in cell behavior.

A paradoxical teratogenic mechanism for retinoic acid.

Retinoic acid, an active metabolite of vitamin A, plays essential signaling roles in mammalian embryogenesis. Nevertheless, it has long been recognized that overexposure to vitamin A or retinoic acid causes widespread teratogenesis in rodents as well as humans. Although it has a short half-life, exposure to high levels of retinoic acid can disrupt development of yet-to-be formed organs, including the metanephros, the embryonic organ which normally differentiates into the mature kidney. Paradoxically, it is known that either an excess or a deficiency of retinoic acid results in similar malformations in some organs, including the mammalian kidney. Accordingly, we hypothesized that excess retinoic acid is teratogenic by inducing a longer lasting, local retinoic acid deficiency. This idea was tested in an established in vivo mouse model in which exposure to excess retinoic acid well before metanephric rudiments exist leads to failure of kidney formation several days later. Results showed that teratogen exposure was followed by decreased levels of Raldh transcripts encoding retinoic acid-synthesizing enzymes and increased levels of Cyp26a1 and Cyp26b1 mRNAs encoding enzymes that catabolize retinoic acid. Concomitantly, there was significant reduction in retinoic acid levels in whole embryos and kidney rudiments. Restoration of retinoic acid levels by maternal supplementation with low doses of retinoic acid following the teratogenic insult rescued metanephric kidney development and abrogated several extrarenal developmental defects. This previously undescribed and unsuspected mechanism provides insight into the molecular pathway of retinoic acid-induced teratogenesis.