Both Strands of siRNA Have Potential to Guide Posttranscriptional Gene Silencing in Mammalian Cells

Despite the widespread application of RNA interference (RNAi) as a research tool for diverse purposes, the key step of strand selection of siRNAs during the formation of RNA-induced silencing complex (RISC) remains poorly understood. Here, using siRNAs targeted to the complementary region of Survivin and the effector protease receptor 1 (EPR-1), we show that both strands of the siRNA duplex can find their target mRNA and are equally eligible for assembly into Argonaute 2 (Ago2) of RISC in HEK293 cells. Transfection of the synthetic siRNA duplexes with different thermodynamic profiles or short hairpin RNA (shRNA) vectors that generate double-stranded RNAs (dsRNAs), permitting processing specifically from either the 5′ or 3′ end of the incipient siRNA, results in the degradation of the respective target mRNAs of either strand of the siRNA duplex with comparable efficiencies. Thus, while most RNAi reactions may follow the thermodynamic asymmetry rule in strand selection, our study suggests an exceptional mode for certain siRNAs in which both strands of the duplex are competent in sponsoring RNAi, and implies additional factors that might dictate the RNAi targets

Outcome assessment for out-of-hospital cardiac arrest patients in Singapore and Japan with initial shockable rhythm

Abstract Background Singapore and Osaka in Japan have comparable population sizes and prehospital management; however, the frequency of ECPR differs greatly for out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythm. Given this disparity, we hypothesized that the outcomes among the OHCA patients with initial shockable rhythm in Singapore were different from those in Osaka. The aim of this study was to evaluate the outcomes of OHCA patients with initial shockable rhythm in Singapore compared to the expected outcomes derived from Osaka data using machine learning-based prediction models. Methods This was a secondary analysis of two OHCA databases: the Singapore PAROS database (SG-PAROS) and the Osaka-CRITICAL database from Osaka, Japan. This study included adult (18–74 years) OHCA patients with initial shockable rhythm. A machine learning-based prediction model was derived and validated using data from the Osaka-CRITICAL database (derivation data 2012–2017, validation data 2018–2019), and applied to the SG-PAROS database (2010–2016 data), to predict the risk-adjusted probability of favorable neurological outcomes. The observed and expected outcomes were compared using the observed–expected ratio (OE ratio) with 95% confidence intervals (CI). Results From the SG-PAROS database, 1,789 patients were included in the analysis. For OHCA patients who achieved return of spontaneous circulation (ROSC) on hospital arrival, the observed favorable neurological outcome was at the same level as expected (OE ratio: 0.905 [95%CI: 0.784–1.036]). On the other hand, for those who had continued cardiac arrest on hospital arrival, the outcomes were lower than expected (shockable rhythm on hospital arrival, OE ratio: 0.369 [95%CI: 0.258–0.499], and nonshockable rhythm, OE ratio: 0.137 [95%CI: 0.065–0.235]). Conclusion This observational study found that the outcomes for patients with initial shockable rhythm but who did not obtain ROSC on hospital arrival in Singapore were lower than expected from Osaka. We hypothesize this is mainly due to differences in the use of ECPR

Characteristics and outcomes of emergency patients with self-inflicted injuries: A report from ambulance records in Osaka City, Japan

Background: Few studies have evaluated the actual situations of emergency patients with self-inflicted injuries treated by emergency-medical-service (EMS) personnel. Methods: This study retrospectively reviewed population-based ambulance records in Osaka City, Japan, between January 2010 and December 2012, and enrolled emergency patients who suffered from self-inflicted injuries such as poisoning by drugs or gas, cutting/piercing skin, jumping from heights, hanging, and drowning. The endpoint was the annual incidence per 100, 000 populations in Osaka City of emergency patients who presented with self-inflicted injuries by age and sex. Their outcomes including deaths at the scene and hospital arrival were also evaluated. Results: During the study period, a total of 8, 671 patients with 9, 424 incidents of self-inflicted injuries were documented. The annual incidence of self-inflicted injuries was higher among women than men in the whole population and in the age group =50 years (49.0 versus 68.9, P < 0.001). The total number of self-inflicted deaths was 1, 564 (16.6 %), and the overall proportion of self-inflicted deaths was greater among men than women (32.2 % [1075/3340] vs. 7.5 % [451/6027], P < 0.001). The proportion of self-inflicted hanging was 76.7 % [1142/1489], followed by poisoning by carbon monoxide at 57.1 % [56/98] and jumping to death at 47.6 % [254/534]. Discussion: Using large-scale EMS records, we investigated characteristics and outcomes of emergency patients with self-inflicted injuries treated by EMS personnel. Our findings suggested the gender paradox that the proportion of self-inflicted deaths was higher among men than women, while the proportion of non-fatal self-inflicted injuries was higher among women than among men, particularly in the group aged <=49 years. Our findings showing the importance of the prevention for self-inflicted injuries as well as the gender paradox of self-inflicted injuries will provide important epidemiological information to improve psychiatric cares in prehospital emergency settings. Conclusions: In the total population, the annual incidence of self-inflicted injuries responded to by EMS personnel was higher among women than among men. However, the proportion of self-inflicted deaths was greater among men than women, and the most frequent manner among deceased patients was by hanging