Synaptotagmins (Syt) play important roles in Ca2؉ -induced neuroexocytosis. Insulin secretion of the pancreatic ␤-cell is dependent on an increase in intracellular Ca 2؉ ; however, Syt involvement in insulin exocytosis is poorly understood. Reverse transcriptase-polymerase chain reaction studies showed the presence of Syt isoforms III, IV, V, and VII in rat pancreatic islets, whereas Syt isoforms I, II, III, IV, V, VII, and VIII were present in insulin-secreting ␤TC3 cell. Syt III and VII proteins were identified in rat islets and ␤TC3 and RINm5F ␤-cells by immunoblotting. Confocal microscopy showed that Syt III and VII co-localized with insulin-containing secretory granules. Two-fold overexpression of Syt III in RINm5F ␤-cell (Syt III cell) was achieved by stable transfection, which conferred greater Ca 2؉ sensitivity for exocytosis, and resulted in increased insulin secretion. Glyceraldehyde ؉ carbachol-induced insulin secretion in Syt III cells was 2.5-fold higher than control empty vector cells, whereas potassium-induced secretion was 6-fold higher. In permeabilized Syt III cells, Ca 2؉ -induced and mastoparan-induced insulin secretion was also increased. In Syt VII-overexpressing RINm5F ␤-cells, there was amplification of carbachol-induced insulin secretion in intact cells and of Ca 2؉ -induced and mastoparan-induced insulin secretion in permeabilized cells. In conclusion, Syt III/VII are located in insulincontaining secretory granules, and we suggest that Syt III/VII may be the Ca 2؉ sensor or one of the Ca 2؉ sensors for insulin exocytosis of the ␤-cell.Insulin exocytosis from the ␤-cell of the islets of Langerhans is stimulated by various physiological secretagogues that include glucose, amino acids, and receptor-mediated agonists such as acetylcholine, cholecystokinin, and glucagon like-peptide 1 (1-7). A common mechanism of action for these secretagogues is to cause an increase in cytosolic Ca 2ϩ . Elevation of intracellular Ca 2ϩ is due to an influx of extracellular Ca 2ϩ through voltage-dependent L-type Ca 2ϩ channel and/or mobilization of intracellular Ca 2ϩ from the endoplasmic reticulum (8 -17). However, the mechanisms by which Ca 2ϩ induces insulin granule fusion with the plasma membrane of ␤-cell remain unclear (1,16,18,20,21).1 is a family of membrane proteins initially found to be expressed in brain. At the present, 11 members of Syt have been identified (22,23). The Syt molecule has a single transmembrane domain and two Ca 2ϩ regulatory C 2 domains. The C 2 domains mediate Ca 2ϩ -dependent and Ca 2ϩ -independent interactions with target molecules that may regulate membrane fusion and membrane budding reactions (24,25). Literature concerning the expression and functions of Syt in pancreatic ␤-cell is very limited and contradictory. In an earlier study (26), Syt was found in the non-␤-cell of the islet mantle, but not in the ␤-cell, using a non-isoform-specific antibody, and the mRNAs of Syt A and B were absent in mouse pancreatic ␤-cell and RINm5F cells as demonstrated by in situ hybridization...

In a large multicenter series of Y-stent coiling for bifurcation aneurysms, there were low complication rates and excellent clinical and angiographic outcomes.

Onyx AVM embolization requires increased fluoroscopy and procedure times compared with nBCA. Further investigation is necessary to justify increased radiation exposure and procedure time associated with Onyx.

Cerebral Aneurysms (CAs) are characterized by a pathological wall structure with internal elastic lamina and media disruption which leads to focal weakened pouches of the arterial wall. The prevalence of unruptured CAs is estimated to be 2-5% in the general population. During the past few decades, the pathophysiological mechanisms behind the formation, growth and rupture of CAs have been the focus of numerous research studies. In this review, the inflammatory pathways, genetics and risk factors for the formation, growth and rupture of CAs are summarized. In addition, the concepts of geometrical indices, flow patterns and fluid dynamics that govern CA development are discussed.

Human endothelial cells express thrombin receptors and PAR-2, the two known members of the family of protease-activated G protein-coupled receptors. Because previous studies have shown that the biology of the human thrombin receptor varies according to the cell in which it is expressed, we have taken advantage of the presence of both receptors in endothelial cells to examine the enabling and disabling interactions with candidate proteases likely to be encountered in and around the vascular space to compare the responses elicited by the two receptors when they are present in the same cell and to compare the mechanisms of thrombin receptor and PAR-2 clearance and replacement in a common cellular environment. Of the proteases that were tested, only trypsin activated both receptors. Cathepsin G, which disables thrombin receptors, had no effect on PAR-2, while urokinase, kallikrein, and coagulation factors IXa, Xa, XIa, and XIIa neither substantially activated nor noticeably disabled either receptor. Like thrombin receptors, activation of PAR-2 caused pertussis toxin-sensitive phospholipase C activation as well as activation of phospholipase A 2 , leading to the release of PGI 2 . Concurrent activation of both receptors caused a greater response than activation of either alone. It also abolished a subsequent response to the PAR-2 agonist peptide, SLIGRL, while only partially inhibiting the response to the agonist peptide, SFLLRN, which activates both receptors. After proteolytic or nonproteolytic activation, PAR-2, like thrombin receptors, was cleared from the endothelial cell surface and then rapidly replaced with new receptors by a process that does not require protein synthesis. Selective activation of either receptor had no effect on the clearance of the other. These results suggest that the expression of both thrombin receptors and PAR-2 on endothelial cells serves more to extend the range of proteases to which the cells can respond than it does to extend the range of potential responses. The results also show that proteases that can disable these receptors can distinguish between them, just as do most of the proteases that activate them. Finally, the residual response to SFLLRN after activation of thrombin receptors and PAR-2 raises the possibility that a third, as yet unidentified member of this family is expressed on endothelial cells, one that is activated by neither thrombin nor trypsin.

Our initial experience with treatment of high cervical and skull base dissections with the PED appears to show that this technique may be a safe and viable treatment option. However, long-term results are needed to fully evaluate the efficacy of such treatment.

Background and Purpose: Stent-assisted coil embolization using the new generation Neuroform Atlas Stent System has shown promising safety and efficacy. The primary study results of the anterior circulation aneurysm cohort of the treatment of wide-neck, saccular, intracranial, aneurysms with the Neuroform Atlas Stent System (ATLAS trial [Safety and Effectiveness of the Treatment of Wide Neck, Saccular Intracranial Aneurysms With the Neuroform Atlas Stent System]) are presented. Methods: ATLAS IDE trial (Investigational Device Exemption) is a prospective, multicenter, single-arm, open-label study of wide-neck (neck ≥4 mm or dome-to-neck ratio <2) intracranial aneurysms in the anterior circulation treated with the Neuroform Atlas Stent and approved coils. The primary efficacy end point was complete aneurysm occlusion (Raymond-Roy class 1) on 12-month angiography, in the absence of retreatment or parent artery stenosis (>50%) at the target location. The primary safety end point was any major stroke or ipsilateral stroke or neurological death within 12 months. Adjudication of the primary end points was performed by an independent Imaging Core Laboratory and the Clinical Events Committee. Results: A total of 182 patients with wide-neck anterior circulation aneurysms at 25 US centers were enrolled. The mean age was 60.3±11.4 years, 73.1% (133/182) women, and 80.8% (147/182) white. Mean aneurysm size was 6.1±2.2 mm, mean neck width was 4.1±1.2 mm, and mean dome-to-neck ratio was 1.2±0.3. The most frequent aneurysm locations were the anterior communicating artery (64/182, 35.2%), internal carotid artery ophthalmic artery segment (29/182, 15.9%), and middle cerebral artery bifurcation (27/182, 14.8%). Stents were placed in the anticipated anatomic location in all patients. The study met both primary safety and efficacy end points. The composite primary efficacy end point of complete aneurysm occlusion (Raymond-Roy 1) without parent artery stenosis or aneurysm retreatment was achieved in 84.7% (95% CI, 78.6%–90.9%) of patients. Overall, 4.4% (8/182, 95% CI, 1.9%–8.5%) of patients experienced a primary safety end point of major ipsilateral stroke or neurological death. Conclusions: In the ATLAS IDE anterior circulation aneurysm cohort premarket approval study, the Neuroform Atlas stent with adjunctive coiling met the primary end points and demonstrated high rates of long-term complete aneurysm occlusion at 12 months, with 100% technical success and <5% morbidity. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02340585.

In a case-control study of patients with multiple cerebral aneurysms, increased bottleneck factor and height-width ratio were consistently associated with rupture.