Signals and posttranslational modifications regulating the decapping step in mRNA degradation pathways are poorly defined. In this study we reveal the importance of K63-linked ubiquitylation for the ...assembly of decapping factors, P-body formation, and constitutive decay of instable mRNAs encoding mediators of inflammation by various experimental approaches. K63-branched ubiquitin chains also regulate IL-1-inducible phosphorylation of the P-body component DCP1a. The E3 ligase TRAF6 binds to DCP1a and indirectly regulates DCP1a phosphorylation, expression of decapping factors, and gene-specific mRNA decay. Mutation of six C-terminal lysines of DCP1a suppresses decapping activity and impairs the interaction with the mRNA decay factors DCP2, EDC4, and XRN1, but not EDC3, thus remodeling P-body architecture. The usage of ubiquitin chains for the proper assembly and function of the decay-competent mammalian decapping complex suggests an additional layer of control to allow a coordinated function of decapping activities and mRNA metabolism in higher eukaryotes.
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•K63-linked ubiquitin regulates DCP1a phosphorylation, P-body assembly, and mRNA decay•DCP1a is ubiquitylated and binds to TRAF6 and to ubiquitin binding domains•TRAF6 regulates decapping factors and mRNA decay at multiple levels•DCP1a C-terminal lysines participate in decapping activity and P-body remodeling
Tenekeci et al. (2016) describe the relevance of K63-linked ubiquitylation and TRAF6 as regulators of decapping complex assembly and phosphorylation, formation of cytosolic processing (P)-bodies, and the decay of instable inflammatory RNAs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUNDEarly outcome prediction in out-of-hospital cardiac arrest is still a challenge. End-tidal carbon dioxide (ETCO2) has been shown to be a reliable parameter to reflect the quality of ...cardiopulmonary resuscitation and the chance of return of spontaneous circulation (ROSC).
OBJECTIVESThis study assessed the validity of early capnography as a predictive factor for ROSC and survival in out-of-hospital cardiac arrest victims with an underlying nonshockable rhythm.
DESIGNRetrospective observational study.
SETTING/PATIENTSDuring a 2-year observational period, data from 2223 out-of-hospital cardiac arrest victims within the city of Vienna were analysed. The focus was on the following patientsage more than 18 years, an underlying nonshockable rhythm, and advanced airway management within the first 15 min of advanced life support with subsequent capnography.
INTERVENTIONNo specific intervention was set in this observational study.
MAIN OUTCOME MEASURESThe first measured ETCO2, assessed immediately after placement of an advanced airway, was used for further analysis. The primary outcome was defined as sustained ROSC, and the secondary outcome was 30-day survival.
RESULTSA total of 526 patients met the inclusion criteria. These were stratified into three groups according to initial ETCO2 values (<20, 20 to 45, >45 mmHg). Baseline data and resuscitation factors were similar among all groups. The odds of sustained ROSC and survival were significantly higher for patients presenting with higher values of initial ETCO2 (>45 mmHg)3.59 95% CI, 2.19 to 5.85 P = 0.001 and 5.02 95% CI, 2.25 to 11.23 P = 0.001, respectively. On the contrary ETCO2 levels less than 20 mmHg were associated with significantly poorer outcomes.
CONCLUSIONPatients with a nonshockable out-of-hospital cardiac arrest who presented with higher values of initial ETCO2 had an increased chance of sustained ROSC and survival. This finding could help decision making as regards continuation of resuscitation efforts.
Abstract Aim Recently three large post product placement studies, comparing mechanical chest compression (cc) devices to those who received manual cc, found equivalent outcome results for both ...groups. Thus the question arises whether those results could be replicated using the devices on a daily routine. Methods We prospectively enrolled 948 patients over a 12 months period. Chi-Square test and Mann–Whitney- U test were used to assess differences between “manual” and “mechanical” cc subgroups. Uni- and multivariate Cox regression hazard analysis were used to assess the influence of cc type on survival. Results A mechanical cc device was used in 30.1% ( n = 283) cases. Patients who received mechanical cc had a significantly worse neurological outcome – measured in cerebral performance category (CPC) – than the manual cc group (56.8% vs. 78.6%, p = 0.009). Patients receiving mechanical cc were significantly younger, more were male and were more likely to have bystander CPR and an initially shock-able ECG rhythm. There was no difference in the quality of CPR that might explain the worse outcome in mechanical cc patients. Conclusion Even with high quality CPR in both, manual and mechanical cc groups, outcome in patients who received mechanical cc was significantly worse. The anticipated benefits of a higher compression ratio and a steadier compression depth of a mechanical cc device remain uncertain. In this study selection for mechanical cc was not standardized, and was non-random. This merits further investigation. Further research on how mechanical cc is chosen and used should be considered. Clinical trial registration: https://ekmeduniwien.at/core/catalog/2013/ (EK-Nr:1221/2013)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Acute pulmonary embolism is a frequent potentially reversible cause of sudden cardiac arrest. The early diagnosis is challenging but essential for further treatment. New therapeutic options in ...resuscitation, such as extracorporeal resuscitation, are leading to frequent transports of patients to emergency rooms with ongoing resuscitation. A transoesophageal echo performed during resuscitation can give hints for reversible causes for the cardiac arrest. We present a case of a 40-year-old female patient who was transferred to our department with ongoing resuscitation and received a transoesophageal echo immediately on arrival. The examination showed a massive intracardiac thrombus. The subsequent thrombolysis and following resuscitation were observed and documented via transoesophageal echo.
Pediatric cervical spine clearance guidelines should reduce computed tomography (CT) usage in combined pediatric and adult trauma centers biased by adult CT clearance.
Cervical spine clearance under ...age 15 years was compared 12 months before (128 patients) and after (105 patients) guideline implementation, emphasizing National Emergency X-Radiography Utilization Study (NEXUS) criteria when appropriate.
CT scans in patients clearable by NEXUS criteria decreased 23% (p = 0.01) and decreased by 16% in cases where radiography other than CT was indicated by guidelines (p = 0.01).
Guideline implementation can have an immediate effect in decreasing pediatric cervical spine CT usage and should improve across time.
Care management study, level IV.
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