Perioperative Cardiac Arrests

Perioperative cardiac arrests represent the most serious complication of anesthesia and surgery. It is believed that the incidence and mortality of cardiac arrest has declined, however, a more recent review questioned whether these rates have changed over the last 5 decades. It is difficult to compare the reports from different epochs, because medical practice has advanced, surgical acuity increased, and patients in extremes of age undergo surgery today. In the present article we review the information regarding the incidence of perioperative cardiac arrests and predictors of survival covering the period since the first comprehensive report by Beecher and Todd in 1954. We focus on our publications that report perioperative cardiac arrest at Mayo Clinic for adult noncardiac surgery, during regional anesthesia, and arrests in our pediatric surgical practice

TRAIP is a regulator of the spindle assembly checkpoint.

Accurate chromosome segregation during mitosis is temporally and spatially coordinated by fidelity-monitoring checkpoint systems. Deficiencies in these checkpoint systems can lead to chromosome segregation errors and aneuploidy, and promote tumorigenesis. Here, we report that the TRAF-interacting protein (TRAIP), a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation, is localized close to mitotic chromosomes. Its knockdown in HeLa cells by RNA interference (RNAi) decreased the time of early mitosis progression from nuclear envelope breakdown (NEB) to anaphase onset and increased the percentages of chromosome alignment defects in metaphase and lagging chromosomes in anaphase compared with those of control cells. The decrease in progression time was corrected by the expression of wild-type but not a ubiquitin-ligase-deficient form of TRAIP. TRAIP-depleted cells bypassed taxol-induced mitotic arrest and displayed significantly reduced kinetochore levels of MAD2 (also known as MAD2L1) but not of other spindle checkpoint proteins in the presence of nocodazole. These results imply that TRAIP regulates the spindle assembly checkpoint, MAD2 abundance at kinetochores and the accurate cellular distribution of chromosomes. The TRAIP ubiquitin ligase activity is functionally required for the spindle assembly checkpoint control

Pediatric surgical extracorporeal membrane oxygenation - a case series

Objective. To review demographic and procedural factors and their association with weaning rate and survival from extracorporeal membrane oxygenation (ECMO) in pediatric patients undergoing repair of cardiac malformations. Methods. The hospital records of children requiring ECMO during cardiac operation due to failure to wean from cardio-pulmonary by pass (CPB) were retrospectively reviewed, and an analysis of variables affecting survival was performed. Results. Thirty-five pediatric patients between January 1, 2000 and December 31, 2006 required ECMO for cardiopulmonary support during cardiac operations. ECMO survival was 54.3% and was comparable across all age groups. The lowest pH during ECMO treatment was the only predictor of mortality (P = 0.006). No other patient, surgical or anesthetic, factor was associated with either weaning from ECMO or hospital survival. Conclusions. No clear risk factor could be identified for survival from ECMO in our pediatric patients who underwent cardiac surgery and failed weaning from cardiopulmonary bypass

Ontology-Based Support for Security Requirements Specification Process

The security requirements specification (SRS) is an integral aspect of the development of secured information systems and entails the formal documentation of the security needs of a system in a correct and consistent way. However, in many cases there is lack of sufficiently experienced security experts or security requirements (SR) engineer within an organization, which limits the quality of SR that are specified. This paper presents an approach that leverages ontologies and requirements boilerplates in order to alleviate the effect of lack of highly experienced personnel for SRS. It also offers a credible starting point for the SRS process. A preliminary evaluation of the tool prototype – ReqSec tool - was used to demonstrate the approach and to confirm its usability to support the SRS process. The tool helps to reduce the amount of effort required, stimulate discovery of latent security threats, and enables the specification of good quality SR

Functional characterisation of the mammalian NDR1 and NDR2 protein kinases and their regulation by the mammalian Ste20-like kinase MST3

Protein modification is a common regulatory mechanism in order to transduce a signal from one molecule to another. One of the best-studied protein modifications is phosphorylation. The enzymes that are capable of transferring phosphate groups onto other proteins are called protein kinases. Depending on the acceptor group, kinases can be distinguished into tyrosine, serine/threonine and dual-specificity kinases. This work describes the characterisation of human and mouse NDR1 and NDR2 kinases, members of the AGC group of serine/threonine kinases. The NDR protein kinase family is highly conserved between yeast and human, and several members have been shown to be involved in the regulation of cell morphology and the control of cell cycle progression. For example, the yeast NDR kinases Sid2p (Schizosaccharomyces pombe) and Dbf2p (Saccharomyces cerevisiae) are central components of the septation-initiation network and the mitosis exit network, respectively. The closest yeast relatives Cbk1p and Orb6p, members of the regulation of Ace2p transcription and morphogenesis network and Orb6 signalling pathways, are implicated in the coordination of cell cycle progression and cell morphology. This study, as well as studies using worms and flies, provide evidence that not only NDR is conserved, but also the NDR signalling pathway and regulation. Similar to yeast, NDR kinase activation is regulated by phosphorylation at the activation segment phosphorylation site and the hydrophobic motif phosphorylation site. This phosphorylation is regulated by a conserved signaling module consisting of MOB proteins and a STE20–like kinase. Here we show that the STE20-like kinase MST3 activates NDR by phosphorylation specifically at the hydrophobic motif in vitro and in vivo. Furthermore, MOB1A binding is important for the release of autoinhibition and full kinase activation. The data also indicate that NDR is part of a feedback mechanism, which induces cleavage and nuclear translocation of MST3. The data presented here also show that NDR1 and NDR2 are differentially expressed, but regulated in a similar manner. Mouse Ndr1 mRNA is mainly expressed in spleen, thymus and lung, whereas Ndr2 mRNA is more ubiquitously expressed, with the highest levels in the gastrointestinal tract. Both, NDR1 and NDR2, are activated by S100B protein and okadaic acid stimulated phosphorylation; NDR1 and NDR2 are also indistinguishable in the biochemical assays used: membrane targetting, phosphorylation by MST3, and activation by MOB. Further, this work describes the generation and initial characterisation of a mouse model for NDR1 deficiency. Protein analysis using NDR1 knockout mouse embryonic fibroblasts suggest a compensation of the loss of NDR1 by upregulation of NDR2 expression