Dram1 regulates DNA damage-induced alternative autophagy

Autophagy is an evolutionarily conserved process that degrades subcellular constituents. Mammalian cells undergo two types of autophagy; Atg5-dependent conventional autophagy and Atg5-independent alternative autophagy, and the molecules required for the latter type of autophagy are largely unknown. In this study, we analyzed the molecular mechanisms of genotoxic stress-induced alternative autophagy, and identified the essential role of p53 and damage-regulated autophagy modulator (Dram1). Dram1 was sufficient to induce alternative autophagy. In the mechanism of alternative autophagy, Dram1 functions in the closure of isolation membranes downstream of p53. These findings indicate that Dram1 plays a pivotal role in genotoxic stress-induced alternative autophagy

The impact of blood type O on mortality of severe trauma patients: a retrospective observational study

Abstract Background Recent studies have implicated the differences in the ABO blood system as a potential risk for various diseases, including hemostatic disorders and hemorrhage. In this study, we evaluated the impact of the difference in the ABO blood type on mortality in patients with severe trauma. Methods A retrospective observational study was conducted in two tertiary emergency critical care medical centers in Japan. Patients with trauma with an Injury Severity Score (ISS) > 15 were included. The association between the different blood types (type O versus other blood types) and the outcomes of all-cause mortality, cause-specific mortalities (exsanguination, traumatic brain injury, and others), ventilator-free days (VFD), and total transfusion volume were evaluated using univariate and multivariate competing-risk regression models. Moreover, the impact of blood type O on the outcomes was assessed using regression coefficients in the multivariate analysis adjusted for age, ISS, and the Revised Trauma Score (RTS). Results A total of 901 patients were included in this study. The study population was divided based on the ABO blood type: type O, 284 (32%); type A, 285 (32%); type B, 209 (23%); and type AB, 123 (13%). Blood type O was associated with high mortality (28% in patients with blood type O versus 11% in patients with other blood types; p <  0.001). Moreover, this association was observed in a multivariate model (adjusted odds ratio = 2.86, 95% confidence interval 1.84–4.46; p <  0.001). The impact of blood type O on all-cause in-hospital mortality was comparable to 12 increases in the ISS, 1.5 decreases in the RTS, and 26 increases in age. Furthermore, blood type O was significantly associated with higher cause-specific mortalities and shorter VFD compared with the other blood types; however, a significant difference was not observed in the transfusion volume between the two groups. Conclusions Blood type O was significantly associated with high mortality in severe trauma patients and might have a great impact on outcomes. Further studies elucidating the mechanism underlying this association are warranted to develop the appropriate intervention

Additional file 2: of The impact of blood type O on mortality of severe trauma patients: a retrospective observational study

Table S1. Multivariate analysis of the factors influencing outcomes and the comparison of explanatory variables. (DOCX 72 kb

Additional file 1: of The impact of blood type O on mortality of severe trauma patients: a retrospective observational study

Figure S1. The diagonal line represents the line of perfect fit between observed and predicted risk. (TIFF 2540 kb