Replication Protein A (RPA) Mediates Radio-Resistance of Glioblastoma Cancer Stem-Like Cells

Glioblastoma (GBM) is among the deadliest of solid tumors with median survival rates of approximately 12–15 months despite maximal therapeutic intervention. A rare population of self-renewing cells referred to as GBM cancer stem-like cells (GSCs) are believed to be the source of inevitable recurrence in GBM. GSCs exhibit preferential activation of the DNA damage response pathway (DDR) and evade ionizing radiation (IR) therapy by superior execution of DNA repair compared to their differentiated counterparts, differentiated GBM cells (DGCs). Replication Protein A (RPA) plays a central role in most of the DNA metabolic processes essential for genomic stability, including DNA repair. Here, we show that RPA is preferentially expressed by GSCs and high RPA expression informs poor glioma patient survival. RPA loss either by shRNA-mediated silencing or chemical inhibition impairs GSCs’ survival and self-renewal and most importantly, sensitizes these cells to IR. This newly uncovered role of RPA in GSCs supports its potential clinical significance as a druggable biomarker in GBM

Immediate psychological impact on citizen responders dispatched through a mobile application to out-of-hospital cardiac arrests

Background: Activating citizen responders may increase survival after out-of-hospital cardiac arrest (OHCA) but could induce significant psychological impact on the citizen responders. We examined psychological impact among citizen responders within the first days following resuscitation attempt. Methods and Results: A mobile phone application to activate citizen responders to perform cardiopulmonary resuscitation (CPR) was implemented in the Capital Region of Denmark. All dispatched citizen responders (September 2017 to May 2019) received a survey 90 minutes after an alarm, including self-rating of perceived psychological impact on a scale of 1–4.Of 5,395 included citizen responders, most (88.6%) completed the survey within 24 hours.The majority reported no psychological impact (68.6%), whereas 24.7%, 5.5% and 1.2% reported low, moderate, or severe impact, respectively. Severe impact was more commonly reported in the following groups: No CPR training (3.8% vs 1.2%, p = 0.02), age < 30 years (2.0% vs 0.9%, p < 0.001), female sex (1.8% vs 0.7%, p < 0.001), provided CPR (2.7% vs 1.0%, p < 0.001), and arrived prior to the emergency medical services (EMS) (2.8% vs 0.7%, p < 0.001) compared to no to moderate impact.Chi square test, Mann-Whitney U test, Fischer’s exact test and a logistic regression model were used to assess differences in psychological impact across groups. Conclusion: Very few citizen responders reported severe psychological impact. Lack of prior CPR training, younger age, female sex, performing CPR and arrival prior to the EMS were associated with greater psychological impact. Though very few citizen responders reported severe impact, the possibility of professional debriefing should be considered in citizen responder programs

Out-of-hospital cardiac arrest:Does rurality decrease chances of survival?

BACKGROUND: Geographical setting is seldomly taken into account when investigating out-of-hospital cardiac arrest (OHCA). It is a common notion that living in rural areas means a lower chance of fast and effective helpwhen suffering a time-critical event. This retrospective cohort study investigates this hypothesis and compares across healthcare-divided administrative regions. METHODS: We included only witnessed OHCAs to minimize the risk that outcome was predetermined by time to caller arrival and/or recognition. Arrests were divided into public and residential. Residential arrests were categorized according to population density of the area in which they occurred. We investigated incidence, EMS response time and 30-day survival according to area type and subsidiarily by healthcare-divided administrative region. RESULTS: The majority (71%) of 8,579 OHCAs were residential, and 53.2% of all arrests occurred in the most densely populated cell group amongst residential arrests. This group had a median EMS response time of six minutes, whereas the most sparsely populated group had a median of 10 minutes. Public arrests also had a median response time of six minutes. 30-day survival was highest in public arrests (38.5%, [95% CI 36.9;40.1]), and varied only slightly with no statistical significance between OHCAs in densely and sparsely populated areas from 14.8% (95% CI 14.4;15.2) and 13.4% (95% CI 12.2;14.7). CONCLUSION: Our study demonstrates that while EMS response times in Denmark are longer in the rural areas, there is no statistically significant decrease in survival compared to the most densely populated areas

Contemporary levels of cardiopulmonary resuscitation training in Denmark

AIM: Many efforts have been made to train the Danish population in cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use. We assessed CPR and AED training levels among the broad Danish population and volunteer responders. METHODS: In November 2018, an electronic cross-sectional survey was sent to (1) a representative sample of the general Danish population (by YouGov) and (2) all volunteer responders in the Capital Region of Denmark. RESULTS: A total of 2,085 people from the general population and 7,768 volunteer responders (response rate 36%) completed the survey. Comparing the general Danish population with volunteer responders, 81.0% (95% CI 79.2–82.7%) vs. 99.2% (95% CI 99.0–99.4%) p < 0.001 reported CPR training, and 54.0% (95% CI 51.8; 56.2) vs. 89.5% (95% CI 88.9–90.2) p < 0.001 reported AED training, at some point in life. In the general population, the unemployed and the self-employed had the lowest proportion of training with CPR training at 71.9% (95% CI 68.3–75.4%) and 65.4% (95% CI 53.8–75.8%) and AED training at 39.0% (95% CI 35.2–42.9%) and 34.6% (95% CI 24.2–46.2%), respectively. Applicable to both populations, the workplace was the most frequent training provider. Among 18–29-year-olds in the general population, most reported training when acquiring a driver's license. CONCLUSIONS: A large majority of the Danish population and volunteer responders reported previous CPR/AED training. Mandatory training when acquiring a driver's license and training through the workplace seems to disseminate CPR/AED training effectively. However, new strategies reaching the unemployed and self-employed are warranted to ensure equal access