Background:The pathogenic role of phosphorylation of ␣-synuclein in Parkinson disease remains unclear. Results: Ser-129-substituted ␣-synuclein was expressed in transgenic C. elegans. Nonphosphorylatable (S129A) ␣-synuclein showed severe defects. The level of membrane-bound ␣-synuclein was increased in S129A-␣-synuclein. Conclusion: Ser-129 phosphorylation of ␣-synuclein attenuates neuronal dysfunction and downstream stress response by lowering the membrane binding property. Significance: Phosphorylation of ␣-synuclein is protective against neurotoxicity.

Aoki et al.: Utility of the signal intensity ratio of the spleen and myocardium (SMR) on T2-weighted short tau inversion recovery black-blood (T2-STIR BB) images compared to semi-quantitative analysis in patients with images with diffuse high T2 signal intensity, such as that with Takotsubo cardiomyopathy, cardiac amyloidosis, hypereosinophilic myocarditis, and apical hypertrophic cardiomyopathy.

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Background Catheter ablation of atrial fibrillation (AF) is associated with risks of silent cerebral events. However, the timing of intraprocedural micro-embolic events or differences between open-irrigated radiofrequency (RF) and cryoballoon (Cryo) ablation are unclear. Newly developed real-time carotid artery Doppler is a simple non-invasive method to detect micro-embolic signals (MESs) during ablation. Objective We investigated the timing of detecting MESs during RF and Cryo ablation of AF. Methods During the first pulmonary vein isolation (PVI) session of AF, MESs were monitored by real-time carotid artery Doppler monitoring throughout the procedure. The MES counts were collected and evaluated separately during the different steps of the procedure (Figure). Results Thirty-three AF patients (RF/Cryo: 22/11 cases, 9 females, 69.5±11.6 y.o) were included. PVI was successfully accomplished in all patients with no major complications. The MES count was significantly greater in the RF group than Cryo group (table). In both groups, left atrial (LA) access (interatrial puncture) and sheaths insertion to the LA generated a significant number of MESs (RF: 1690 of 9116 MESs [18.5% of the total MESs], Cryo: 793 of 2285 MESs [34.7%]). In the RF group, MESs were observed incessantly during PVI (Figure). The LA dwell time was significantly longer in the RF group than Cryo group (table). In the RF group, the MES count was significantly greater in the longer LA dwell time group (LA dwell time >130min) than the shorter group (464.2±179.7 vs 302.6±138.2: P=0.049). During the cryo-applications in the Cryo group, the MESs were greatest during the first cryoballoon application (625 of 2285 MESs [27.4%]). Conclusions There were more MESs during RF ablation than cryoablation. MESs were recorded during a variety of steps throughout the procedure. In the RF group, most of MESs were recorded incessantly during radiofrequency ablation and greater number of MESs were recorded in patients with longer LA dwell time. In the Cryo group, most of MESs occurred during phases with a high probability of gaseous emboli. Funding Acknowledgement Type of funding source: None

Background The prognosis, the underlying substrate and clinical outcomes of treatment are unclear in patients with cardiac sarcoidosis (CS)-related ventricular tachycardia (VT). Objective This study investigated the prognosis and the relationship between electroanatomical mapping (EAM) and imaging findings in patients with CS-related VT. Methods A total of 203 CS patients (Age 68.1±11.6 years, 87 males) were enrolled at two tertiary care medical centers between 2000 and 2018. All met the 2016 Japanese Circulation Society guidelines for diagnosis of CS. They were followed for a composite of major adverse cardiac events (MACE) including cardiac death, heart transplantation, unscheduled hospitalization for heart failure, and life-threatening ventricular arrhythmias. Distribution of late gadolinium enhancement (LGE) on cardiac MRI (CMR) and/or an abnormal myocardial 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography at diagnosis were examined. The relationship between EAM and the image findings were also analyzed in patients with radiofrequency ablation (RFA) for VT. Results During a median follow-up of 53 months, 87 of the 203 patients (43%) experienced a MACE. Baseline factors associated with MACE were presence of sustained VT (HR, 2.43, 95% CI 1.54–3.85, P<0.001), left ventricular ejection fraction below 50% (HR, 1.95 95% CI 1.07–3.56, P=0.029), and abnormal myocardial FDG uptake (HR, 2.42 95% CI 1.04–5.61, P=0.039). Overall, 69 of the 203 patients (34%) experienced sustained VT. Abnormal myocardial FDG uptake was significantly more prevalent in patients with VT than in those without (92.7% vs. 78.5%, P=0.02). A total of 25 patients (9.9%) required RFA for CS-related VT (Age 64.0±8.7 years, 12 males, 1.32±0.56 RFAs per patient). Abnormal electrocardiograms (EGM) were observed in 22 of the 25 patients (88%). LGE was more frequent than abnormal FDG uptake in areas with an abnormal EGM (77% vs. 41%; P=0.002). Over a mean follow-up period of 67-months, 13 of the 25 patients with RFA (52%) remained free of VT episodes (Figure). VT recurred in nine of the 12 patients with RFA and in 17 of the 47 patients without RFA, but was suppressed by intensive pharmacologic therapy such as the combined use of amiodarone and sotalol. In patients with CS-related VT, survival without experiencing a MACE did not differ in participants with or without RFA. Conclusions In our 203 CS patients, sustained VT and abnormal FDG uptake were associated with worse cardiac outcomes. The prevalence of abnormal FDG uptake was significantly higher in patients with CS-related VT, LGE on CMR was more frequent within localized areas of an abnormal EGM, suggesting that both scar itself and the associated inflammation were involved in the pathogenesis of CS-related VT. Successful RFA of CS-related VT is still challenging, and recurrence is common. Preprocedural CMR can be useful in detecting abnormal EGMs that are potential targets for substrate ablation. Funding Acknowledgement Type of funding source: None