In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

Objective:To explore the risk and influencing factors of atrial fibrillation (AF) due to ivabradine.Methods:The database of US FDA Adverse Event Reporting System (FAERS) was searched and the drug-related adverse event (AE) reports from the 2nd quarter of 2015 to the 4th quarter of 2019 were extracted. According to the first suspicious drug, the reports were divided into ivabradine group and other drugs group, which were further divided into AF event group and non AF event group, respectively. The signal intensity of AF events related to ivabradine was screened and statistically analyzed by reporting odds ratio ( ROR). If the number of AF events was more than 3 and the lower limit of 95% confidence interval ( CI) of ROR was more than 1, the AF signal was positive. The stability of the results was evaluated by subgroup analysis and sensitivity analysis and the adjusted ROR value was calculated using logistic regression model in order to reduce the influence of confounding factors. The differences of clinical characteristics such as age, gender, dose, and indications between patients in the AF event group and non AF event group were compared. The clinical characteristics with significant difference ( P<0.05) were enrolled in the multivariate logistic regression model to analyze the influencing factors of AF induced by ivabradine. Results:A total of 6 019 954 reports were entered in the analysis, including 1 799 cases (0.03%) in the ivabradine group and 6 018 155 cases (99.97%) in the other drugs group. There were 51 cases (2.83%) of AF events in the ivabradine group and 24 266 cases (0.40%) of AF events in the other drugs group. The overall ROR of AF events induced by ivabradine was 7.21 (95 %CI: 5.45-9.52) and the overall adjusted ROR was 6.81 (95 %CI: 5.13-9.02). The results of subgroup analysis and sensitivity analysis were consistent with the results of overall analysis basically. Multivariate logistic regression analysis showed that the risks of AF after ivabradine administration in the 70-79 years old and ≥80 years old patients were higher than that in the <60 years old patients [odds ratio ( OR)=6.525, 95 %CI: 1.896-22.456, P=0.003; OR=4.948, 95 %CI: 1.050- 23.315, P=0.043]. Conclusions:Ivabradine has a risk of AF. Advanced age may be associated with increased risk of ivabradine related AF.

Objective:To explore the risk and influencing factors of atrial fibrillation (AF) due to ivabradine.Methods:The database of US FDA Adverse Event Reporting System (FAERS) was searched and the drug-related adverse event (AE) reports from the 2nd quarter of 2015 to the 4th quarter of 2019 were extracted. According to the first suspicious drug, the reports were divided into ivabradine group and other drugs group, which were further divided into AF event group and non AF event group, respectively. The signal intensity of AF events related to ivabradine was screened and statistically analyzed by reporting odds ratio ( ROR). If the number of AF events was more than 3 and the lower limit of 95% confidence interval ( CI) of ROR was more than 1, the AF signal was positive. The stability of the results was evaluated by subgroup analysis and sensitivity analysis and the adjusted ROR value was calculated using logistic regression model in order to reduce the influence of confounding factors. The differences of clinical characteristics such as age, gender, dose, and indications between patients in the AF event group and non AF event group were compared. The clinical characteristics with significant difference ( P<0.05) were enrolled in the multivariate logistic regression model to analyze the influencing factors of AF induced by ivabradine. Results:A total of 6 019 954 reports were entered in the analysis, including 1 799 cases (0.03%) in the ivabradine group and 6 018 155 cases (99.97%) in the other drugs group. There were 51 cases (2.83%) of AF events in the ivabradine group and 24 266 cases (0.40%) of AF events in the other drugs group. The overall ROR of AF events induced by ivabradine was 7.21 (95 %CI: 5.45-9.52) and the overall adjusted ROR was 6.81 (95 %CI: 5.13-9.02). The results of subgroup analysis and sensitivity analysis were consistent with the results of overall analysis basically. Multivariate logistic regression analysis showed that the risks of AF after ivabradine administration in the 70-79 years old and ≥80 years old patients were higher than that in the <60 years old patients [odds ratio ( OR)=6.525, 95 %CI: 1.896-22.456, P=0.003; OR=4.948, 95 %CI: 1.050- 23.315, P=0.043]. Conclusions:Ivabradine has a risk of AF. Advanced age may be associated with increased risk of ivabradine related AF.

Several digital filtering techniques for correcting baseline drift from ECG signals are presented. A bidirectional filter is introduced, which can cantain baseline drift their filtering performance and realization methods are compared.
Electrocardiography ; instrumentation ; methods ; Filtration ; instrumentation ; Signal Processing, Computer-Assisted ; instrumentation