Using ion mobility spectrometry-mass spectrometry to decipher the conformational and assembly characteristics of the hepatitis B capsid protein.

The structural and functional analysis of the core protein of hepatitis B virus is important for a full understanding of the viral life cycle and the development of novel therapeutic agents. The majority of the core protein (CP149) comprises the capsid assembly domain, and the C-terminal region (residues 150-183) is responsible for nucleic acid binding. Protein monomers associate to form dimeric structural subunits, and helices 3 and 4 (residues 50-111 of the assembly domain) have been shown to be important for this as they constitute the interdimer interface. Here, using mass spectrometry coupled with ion mobility spectrometry, we demonstrate the conformational flexibility of the CP149 dimer. Limited proteolysis was used to locate involvement in this feature to the C-terminal region. A genetically fused CP dimer was found to show decreased disorder, consistent with a more restricted C-terminus at the fusion junction. Incubation of CP149 dimer with heteroaryldihydropyrimidine-1, a small molecule known to interfere with the assembly process, was shown to result in oligomers different in shape to the capsid assembly-competent oligomers of the fused CP dimer. We suggest that heteroaryldihydropyrimidine-1 affects the dynamics of CP149 dimer in solution, likely affecting the ratio between assembly active and inactive states. Therefore, assembly of the less dynamic fused dimer is less readily misdirected by heteroaryldihydropyrimidine-1. These studies of the flexibility and oligomerization properties of hepatitis B virus core protein illustrate both the importance of C-terminal dynamics in function and the utility of gas-phase techniques for structural and dynamical biomolecular analysis

The Automated External Defibrillator : Heterogeneity of Legislation, Mapping and Use across Europe. New Insights from the ENSURE Study

Introduction: The rapid use of an automated external defibrillator (AED) is crucial for increased survival after an out-of-hospital cardiac arrest (OHCA). Many factors could play a role in limiting the chance of an AED use. We aimed to verify the situation regarding AED legislation, the AED mapping system and first responders (FRs) equipped with an AED across European countries. Methods: We performed a survey across Europe entitled “European Study about AED Use by Lay Rescuers” (ENSURE), asking the national coordinators of the European Registry of Cardiac Arrest (EuReCa) program to complete it. Results: Nineteen European countries replied to the survey request for a population covering 128,297,955 inhabitants. The results revealed that every citizen can use an AED in 15 countries whereas a training certificate was required in three countries. In one country, only EMS personnel were allowed to use an AED. An AED mapping system and FRs equipped with an AED were available in only 11 countries. The AED use rate was 12–59% where AED mapping and FR systems were implemented, which was considerably higher than in other countries (0–7.9%), reflecting the difference in OHCA survival. Conclusions: Our survey highlighted a heterogeneity in AED legislation, AED mapping systems and AED use in Europe, which was reflected in different AED use and survival

Intraosseous Versus Peripheral Intravenous Access During Out-of-Hospital Cardiac Arrest: a Comparison of 30-Day Survival and Neurological Outcome in the French National Registry.

International audiencePurposeTo compare intraosseous access with peripheral venous access on adults out-of-hospital cardiac arrest (OHCA) patients’ clinical outcomes.MethodsA national retrospective multicentre study was conducted based on the French National Cardiac Arrest Registry. Comparison of patients (intraosseous vs. peripheral venous access) was conducted before and after a matching using a propensity score. The propensity score included confounding factors: age, time between the call (T0) to epinephrine (to take account of how quickly vascular access was achieved), the aetiology of OHCA, the shock and the patient initial rhythm at MMT arrival.ResultsA total of 1576 patients received intraosseous access, and 27,280 received peripheral intravenous access. Before matching, OHCA patients with intraosseous access were less likely to survive at all stages (return of spontaneous circulation (ROSC), 0-day survival and 30-day survival). No significant difference in neurological outcome was observed. After propensity score matching, no significant differences in 30-day survival rates (OR = 0.763 [0.473;1.231]) and neurological outcome (OR = 1.296 [0.973;1.726]) were observed. However, intraosseous patients still showed lower likelihood of short-term survival (ROSC and 0-day survival) even after propensity score matching was implemented.ConclusionThe populations we investigated were similar to those of other studies suggesting that intraosseous access is associated with reduced survival and poorer neurological outcome. Our findings suggest that intraosseous access is a comparably effective alternative to peripheral intravenous access for treating OHCA patients on matched populations

The Automated External Defibrillator : Heterogeneity of Legislation, Mapping and Use across Europe. New Insights from the ENSURE Study

Introduction: The rapid use of an automated external defibrillator (AED) is crucial for increased survival after an out-of-hospital cardiac arrest (OHCA). Many factors could play a role in limiting the chance of an AED use. We aimed to verify the situation regarding AED legislation, the AED mapping system and first responders (FRs) equipped with an AED across European countries. Methods: We performed a survey across Europe entitled "European Study about AED Use by Lay Rescuers " (ENSURE), asking the national coordinators of the European Registry of Cardiac Arrest (EuReCa) program to complete it. Results: Nineteen European countries replied to the survey request for a population covering 128,297,955 inhabitants. The results revealed that every citizen can use an AED in 15 countries whereas a training certificate was required in three countries. In one country, only EMS personnel were allowed to use an AED. An AED mapping system and FRs equipped with an AED were available in only 11 countries. The AED use rate was 12-59% where AED mapping and FR systems were implemented, which was considerably higher than in other countries (0-7.9%), reflecting the difference in OHCA survival. Conclusions: Our survey highlighted a heterogeneity in AED legislation, AED mapping systems and AED use in Europe, which was reflected in different AED use and survival.Peer reviewe

The automated external defibrillator: Heterogeneity of legislation, mapping and use across europe. new insights from the ensure study

Introduction: The rapid use of an automated external defibrillator (AED) is crucial for increased survival after an out-of-hospital cardiac arrest (OHCA). Many factors could play a role in limiting the chance of an AED use. We aimed to verify the situation regarding AED legislation, the AED mapping system and first responders (FRs) equipped with an AED across European countries. Methods: We performed a survey across Europe entitled “European Study about AED Use by Lay Rescuers” (ENSURE), asking the national coordinators of the European Registry of Cardiac Arrest (EuReCa) program to complete it. Results: Nineteen European countries replied to the survey re-quest for a population covering 128,297,955 inhabitants. The results revealed that every citizen can use an AED in 15 countries whereas a training certificate was required in three countries. In one country, only EMS personnel were allowed to use an AED. An AED mapping system and FRs equipped with an AED were available in only 11 countries. The AED use rate was 12–59% where AED mapping and FR systems were implemented, which was considerably higher than in other countries (0–7.9%), reflecting the difference in OHCA survival. Conclusions: Our survey highlighted a heterogeneity in AED legislation, AED mapping systems and AED use in Europe, which was re-flected in different AED use and survival