Axin, a negative regulator of Wnt signaling, is a key scaffold protein for the b-catenin destruction complex. It has been previously shown that multiple post-translational modification enzymes regulate the level of Axin. Here, we provide evidence that protein arginine methyltransferase 1 (PRMT1) directly interacts with and methylates the 378th arginine residue of Axin both in vitro and in vivo. We found that the transient expression of PRMT1 led to an increased level of Axin and that knockdown of endogenous PRMT1 by short hairpin RNA reduced the level of Axin. These results suggest that methylation by PRMT1 enhanced the stability of Axin. Methylation of Axin by PRMT1 also seemingly enhanced the interaction between Axin and glycogen synthase kinase 3b, leading to decreased ubiquitination of Axin. Consistent with the role of PRMT1 in the regulation of Axin, knockdown of PRMT1 enhanced the level of cytoplasmic b-catenin as well as b-catenin-dependent transcription activity. In summary, we show that the methylation of Axin occurred in vivo and controlled the stability of Axin. Therefore, methylation of Axin by PRMT1 may serve as a finely tuned regulation mechanism for Wnt/b-catenin signaling.
Objective This study aimed to compare the outcomes of adult out-of-hospital cardiac arrest (OHCA) before and after the coronavirus disease 2019 (COVID-19) outbreak in a large metropolitan city.Methods This before-and-after observational study used a prospective citywide OHCA registry. Adult patients with emergency medical service-treated OHCA, with presumed cardiac etiology, pre-and post-COVID-19 outbreak were enrolled. The study period spanned 2 months, starting from February 18, 2020. The control period was 2 months from February 18, 2019. The primary and secondary outcomes were good neurologic outcome and survival to hospital discharge, respectively. The association between the COVID-19 outbreak and OHCA outcomes was assessed using multivariable logistic regression analysis.
ResultsThis study analyzed 297 OHCA patients (control period, 145; study period, 152). The bystander cardiopulmonary resuscitation rates were 64.8% and 60.5% during the control and study periods, respectively. Response and on-scene times increased by 2 minutes, supraglottic airway use increased by 35.6%, and mechanical chest compression device use increased by 13% post-COVID-19 outbreak. Good neurologic outcome was significantly lower during the study period in overall OHCAs (adjusted odds ratio, 0.23; 95% confidence interval, 0.05-0.98) and in witnessed OHCAs (adjusted odds ratio, 0.14; 95% confidence interval, 0.02-0.90). No significant difference was found in the survival to hospital discharge of OHCA patients between the two periods.
ConclusionDuring the COVID-19 pandemic, the response and on-scene times were longer, and good neurologic outcome was significantly lower than that in the control period.
Background: There is currently a lack of evidence-based postresuscitation or postmortem guidelines for patients with out-of-hospital cardiac arrest (OHCA) in the setting of an emerging infectious disease. This study aimed to develop and validate a multimodal screening tool that aids in predicting the disease confirmation in emergency situations and patients with OHCA during a coronavirus disease 2019 (COVID-19) outbreak. Materials and Methods: We conducted a retrospective, multicenter observational study of adult patients with OHCA in Daegu, Korea. To identify the potential predictors that could be used in screening tools in the emergency department, we applied logistic regression to data collected from March 1 to March 14. The prediction performance of the screening variables was then assessed and validated on the data of patients with OHCA who were treated between February 19 and March 31, 2020. General patient characteristics and hematological findings of the COVID-19-negative and COVID-19-positive groups were compared. We also evaluated confirmation test criteria as predictors for COVID-19 positivity in patients with OHCA. Results: Advanced age, body temperature, and abnormal chest X-ray (CXR) revealed significant predictive ability in the derivation cohort. Of the 184 adult patients with OHCA identified in the validation cohort, 80 patients were included in the analysis. Notably, 9 patients were positive and 71 were negative on the COVID-19 reverse transcription polymerase chain reaction test. Five patients (55.6%) in the COVID-19-positive group had a fever before OHCA, and 12 (16.9%) of the COVID-19-negative group had a fever before OHCA (P = 0.018). Eight patients (88.9%) in the COVID-19-positive group had a CXR indicating pneumonic infiltration. Of the criteria for predicting COVID-19, fever or an abnormal CXR had a sensitivity of 100% (95% confidence interval [CI]: 65.4 -100) and a specificity of 22.5% (95% CI: 13.5 -34.0).
Conclusion:The screening tools that combined fever or abnormal CXR had a good
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