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Background: We aimed to derive a clinical decision rule to identify patients with transient ischemic attack (TIA) or minor stroke most likely to benefit from echocardiography., Methods: This multicentre prospective cohort study enrolled adults diagnosed with TIA/minor stroke in the emergency department who underwent echocardiograms within 90 days, from 13 Canadian academic emergency departments from October 2006 to May 2017. Our outcome was clinically significant echocardiogram findings., Results: In 7149 eligible patients, a clinically significant finding was found in 556 (7.8%). There were a further 2421 (33.9%) with potentially significant findings. History of heart failure (adjusted odds ratio [OR], 3.9) or coronary artery disease (OR, 2.7) were the factors most strongly associated with clinically significant echocardiogram findings, whereas young age, male sex, valvular heart disease, and infarct (any age) on neuroimaging were modestly associated (OR, 1.3-1.9). The model combining these predictors into a score (range: 0-15), had a C-statistic of 0.67 (95% confidence interval [CI], 0.65-0.70). A cut point of 6 points or more classified 6.6% of cases as high likelihood, defined as > 15% for clinically significant echocardiogram findings., Conclusions: Echocardiography is a very useful test in the investigations of patients with TIA/minor stroke. We identified high-risk clinical features-combined to create a clinical decision rule-to identify which patients with TIA/minor stroke are likely to have clinically significant echocardiogram findings requiring an immediate change in management. These patients should have echocardiography prioritized, whereas others may continue to have echocardiography conducted in a less urgent fashion., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency department (ED) and ICU. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications., Methods: We searched Medline, EMBASE, Cochrane, and PubMed from inception to 2 March 2023 for RCTs comparing two or more procedural sedation and analgesia medications in all patients (adults and children >30 days of age) requiring emergent procedures in the ED or ICU. We focused on the outcomes of sedation recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates., Results: We included 82 RCTs (8105 patients, 78 conducted in the ED and four in the ICU) of which 52 studies included adults, 23 included children, and seven included both. Compared with midazolam-opioids, recovery time was shorter with propofol (mean difference 16.3 min, 95% confidence interval [CI] 8.4-24.3 fewer minutes; high certainty), and patient satisfaction was better with ketamine-propofol (mean difference 1.5 points, 95% CI 0.3-2.6 points, high certainty). Regarding AEs, compared with midazolam-opioids, respiratory AEs were less frequent with ketamine (relative risk [RR] 0.55, 95% CI 0.32-0.96; high certainty), gastrointestinal AEs were more common with ketamine-midazolam (RR 3.08, 95% CI 1.15-8.27; high certainty), and neurological AEs were more common with ketamine-propofol (RR 3.68, 95% CI 1.08-12.53; high certainty)., Conclusion: When considering procedural sedation and analgesia in the ED and ICU, compared with midazolam-opioids, sedation recovery time is shorter with propofol, patient satisfaction is better with ketamine-propofol, and respiratory adverse events are less common with ketamine., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Bacteria including Vibrio spp. persist in coastal waters and can contaminate edible seaweeds. Pathogens such as Listeria monocytogenes, shigatoxigenic Escherichia coli (STEC), and Salmonella have been associated with and present serious health risks in minimally processed vegetables including seaweeds. This study evaluated the survival of four pathogens inoculated onto two product forms of sugar kelp subjected to different storage temperatures. The inoculation comprised of a cocktail of two Listeria monocytogenes and STEC strains, two Salmonella serovars, and two Vibrio species. STEC and Vibrio were grown and applied in salt-containing media to simulate preharvest contamination, whereas L. monocytogenes and Salmonella inocula were prepared to simulate postharvest contamination. Samples were stored at 4°C and 10°C for 7 days, and 22°C for 8 h. Microbiological analyses were performed periodically (1, 4, 8, 24 h, etc.) to evaluate the effects of storage temperature on pathogen survival. Pathogen populations decreased under all storage conditions, but survival was greatest for all species at 22°C, with STEC exhibiting significantly less reduction (1.8 log CFU/g) than Salmonella, L. monocytogenes, and Vibrio (3.1, 2.7, and 2.7 log CFU/g, respectively) after storage. The largest population reduction (5.3 log CFU/g) was observed in Vibrio stored at 4°C for 7 days. Regardless of storage temperature, all pathogens remained detectable at the end of the study duration. Results emphasize the need for strict adherence to temperature control for kelp as temperature abuse may support pathogen survival, especially STEC, during storage, and the need for prevention of postharvest contamination, particularly with Salmonella., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We sought to evaluate safety of electrical cardioversion (ECV) for patients with acute atrial fibrillation (AF) or atrial flutter (AFL) in the emergency department (ED)., Methods: This was an analysis of data from 4 multicentre AF/AFL studies conducted from 2008 to 2019 at 23 large EDs. We included adult patients who received attempts at ECV and who had presented acutely after symptom onset. Staff manually reviewed study and clinical records to abstract data., Results: We evaluated 1736 ECV cases with a mean age of 60.1 years and 67.1% male. The overall success of ECV was 90.2% (95% confidence interval 88.7%-91.6%), with 4.9% of patients admitted. ED physicians performed the ECV in 95.2% and provided sedation in 96.5%; 13.9% (12.3%-15.7%) of cases experienced important adverse events that required treatment, and 0.4% were classified as life threatening. Another 5.6% had adverse events that did not require treatment. Logistic regression found that the RAFF-3 study cohort (odds ratio [OR] 2.0), age ≥ 85 years (OR 2.1), coronary artery disease (OR 1.5), midazolam (OR 1.9), and fentanyl (OR 1.5) were associated with important adverse events., Conclusions: This large evaluation of the safety of ECV for acute AF/AFL in the ED found that while serious adverse events were rare, there were a concerning number of events following sedation that required intervention. Physicians should be aware that older age, coronary artery disease, and fentanyl are associated with higher risks of important adverse events. This study provides more information for shared decision making discussions with patients when choosing between drug-shock and shock-only cardioversion strategies., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: We sought to improve care of patients with acute atrial fibrillation (AF) and flutter (AFL) in the emergency department (ED) by implementing the Canadian Association of Emergency Physicians (CAEP) Acute AF/AFL Best Practices Checklist., Methods: We conducted a stepped-wedge cluster randomised trial at 11 large community and academic hospital EDs in 5 Canadian provinces and enrolled consecutive AF/AFL patients. The study intervention was introduction of the CAEP Checklist with the use of a knowledge translation-implementation approach that included behaviour change techniques and organisation/system-level strategies. The primary outcome was length of stay in ED, and secondary outcomes were discharge home, use of rhythm control, adverse events, and 30-day status. Analysis used mixed-effects regression adjusting for covariates., Results: Patient visits in the control (n = 314) and intervention (n = 404) periods were similar with mean age 62.9 years, 54% male, 71% onset < 12 hours, and 86% AF, 14% AFL. We observed a reduction in length of stay of 20.9% (95% confidence interval [CI] 5.5%-33.8%; P = 0.01), an increase in use of rhythm control (adjusted odds ratio [OR] 4.5, 95% CI 1.8-11.6; P = 0.002), and a decrease in use of rate-control medications (OR 0.5, 95% CI 0.2-0.9; P = 0.02). There was no change in adverse events and no strokes or deaths by 30 days., Conclusions: The RAFF-3 trial led to optimised care of AF/AFL patients with decreased ED lengths of stay, increased ED rhythm control by drug or electricity, and no increase in adverse events. Early cardioversion allows AF/AFL patients to quickly resume normal activities., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Invasive mechanical ventilation is often initiated in the ED, and mechanically ventilated patients may be kept in the ED for hours before ICU transfer. Although lung-protective ventilation is beneficial, particularly in ARDS, it remains uncertain how often lung-protective tidal volumes are used in the ED, and whether lung-protective ventilation in this setting impacts patient outcomes., Research Question: What is the association between the use of lung-protective ventilation in the ED and outcomes among invasively ventilated patients?, Study Design and Methods: A retrospective analysis (2011-2017) of a prospective registry from eight EDs enrolling consecutive adult patients (≥ 18 years) who received invasive mechanical ventilation in the ED was performed. Lung-protective ventilation was defined by use of tidal volumes ≤ 8 mL/kg predicted body weight. The primary outcome was hospital mortality. Secondary outcomes included development of ARDS, hospital length of stay, and total hospital costs., Results: The study included 4,174 patients, of whom 2,437 (58.4%) received lung-protective ventilation in the ED. Use of lung-protective ventilation was associated with decreased odds of hospital death (adjusted OR [aOR], 0.91; 95% CI, 0.84-0.96) and development of ARDS (aOR, 0.87; 95% CI, 0.81-0.92). Patients who received lung-protective ventilation in the ED had shorter median duration of mechanical ventilation (4 vs 5 days; P < 0.01), shorter median hospital length of stay (11 vs 14 days; P < .001), and reduced total hospital costs (Can$44,348 vs Can$52,484 [US$34,153 vs US$40,418]; P = .03) compared with patients who received higher tidal volumes., Interpretation: Use of lung-protective ventilation in the ED was associated with important patient- and system-centered outcomes, including lower hospital mortality, decreased incidence of ARDS, lower hospital length of stay, and decreased total costs. Protocol development promoting the regular use of lung-protective ventilation in the ED may be of value., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Acute atrial fibrillation is the most common arrythmia treated in the emergency department. Our primary aim was to compare conversion to sinus rhythm between pharmacological cardioversion followed by electrical cardioversion (drug-shock), and electrical cardioversion alone (shock-only). Our secondary aim was to compare the effectiveness of two pad positions for electrical cardioversion., Methods: We did a partial factorial trial of two protocols for patients with acute atrial fibrillation at 11 academic hospital emergency departments in Canada. We enrolled adult patients with acute atrial fibrillation. Protocol 1 was a randomised, blinded, placebo-controlled comparison of attempted pharmacological cardioversion with intravenous procainamide (15 mg/kg over 30 min) followed by electrical cardioversion if necessary (up to three shocks, each of ≥200 J), and placebo infusion followed by electrical cardioversion. For patients having electrical cardioversion, we used Protocol 2, a randomised, open-label, nested comparison of anteroposterior versus anterolateral pad positions. Patients were randomly assigned (1:1, stratified by study site) for Protocol 1 by on-site research personnel using an online electronic data capture system. Randomisation for Protocol 2 occurred 30 min after drug infusion for patients who had not converted and was stratified by site and Protocol 1 allocation. Patients and all research and emergency department staff were masked to treatment allocation for Protocol 1. The primary outcome was conversion to normal sinus rhythm for at least 30 min at any time after randomisation and up to a point immediately after three shocks. Protocol 1 was analysed by intention to treat and Protocol 2 excluded patients who did not receive electrical cardioversion. This study is registered at ClinicalTrials.gov, number NCT01891058., Findings: Between July 18, 2013, and Oct 17, 2018, we enrolled 396 patients, and none were lost to follow-up. In the drug-shock group (n=204), conversion to sinus rhythm occurred in 196 (96%) patients and in the shock-only group (n=192), conversion occurred in 176 (92%) patients (absolute difference 4%; 95% CI 0-9; p=0·07). The proportion of patients discharged home was 97% (n=198) versus 95% (n=183; p=0·60). 106 (52%) patients in the drug-shock group converted after drug infusion only. No patients had serious adverse events in follow-up. The different pad positions in Protocol 2 (n=244), had similar conversions to sinus rhythm (119 [94%] of 127 in anterolateral group vs 108 [92%] of 117 in anteroposterior group; p=0·68)., Interpretation: Both the drug-shock and shock-only strategies were highly effective, rapid, and safe in restoring sinus rhythm for patients in the emergency department with acute atrial fibrillation, avoiding the need for return to hospital. The drug infusion worked for about half of patients and avoided the resource intensive procedural sedation required for electrical cardioversion. We also found no significant difference between the anterolateral and anteroposterior pad positions for electrical cardioversion. Immediate rhythm control for patients in the emergency department with acute atrial fibrillation leads to excellent outcomes., Funding: Heart and Stroke Foundation of Canada and the Canadian Institutes of Health Research., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Rapid response teams (RRTs) respond to hospitalized patients with deterioration and help determine subsequent management, including ICU admission. In such patients with sepsis and septic shock, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) clinical criteria have a potential role in detection, risk stratification, and prognostication; however, their accuracy in comparison with the systemic inflammatory response syndrome (SIRS)-based septic shock criteria is unknown. We sought to evaluate prognostic accuracy of the Sepsis-3 criteria for in-hospital mortality among infected hospitalized patients with acute deterioration., Methods: Prospectively collected registry data (2012-2016) from two hospitals, including consecutive hospitalized patients with suspected infection seen by the RRT. We compared the Sepsis-3 criteria with the SIRS-based criteria for prediction of in-hospital mortality., Results: Of 1,708 included patients, 418 (24.5%) met the Sepsis-3 septic shock criteria, whereas 545 (31.9%) met the SIRS-based septic shock criteria. Patients meeting the Sepsis-3 septic shock criteria had higher in-hospital mortality (40.9% vs 33.5%; P < .0001), ICU admission (99.5% vs 89.2%; P < .001), and discharge rates to long-term care (66.3% vs 53.7%; P < .0001) than patients meeting the SIRS-based septic shock criteria, respectively. Sensitivity and specificity of the quick Sequential (Sepsis-Related) Organ Failure Assessment were 64.9% and 92.2% for prediction of in-hospital mortality, whereas SIRS criteria had a sensitivity and specificity of 91.6% and 23.6%, respectively., Conclusions: Hospitalized patients with deterioration from suspected infection had higher risk of in-hospital mortality if they met the Sepsis-3 septic shock criteria than the SIRS-based septic shock criteria. Therefore, use of the Sepsis-3 criteria may be preferable in the prognostication and disposition of these patients who are critically ill., (Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Despite evidence supporting the implementation of supervised injection facilities (SIFs) by multiple stakeholders, no evaluation of emergency physicians' attitudes has ever been documented towards such facilities in Canada or internationally. The primary goal of our study was to determine the opinions and perceptions of emergency physicians regarding the implementation of SIFs in Canada., Methods: We conducted a national electronic survey of staff and resident emergency physicians in Canada using an iteratively designed survey tool in consultation with content experts. Invitations to complete the survey were sent via email by the Canadian Association of Emergency Physicians. Inclusion criteria required respondents to have treated an adult patient in a Canadian emergency department within the preceding 6 months. The primary measure was the proportion of respondents who would support, not support or were unsure of supporting SIFs in their community with the secondary measure being the likelihood of respondents to refer patients to a SIF if available., Results: We received 280 responses out of 1353 eligible physicians (20.7%), with the analysis conducted on 250 responses that met inclusion criteria (18.5%). The majority of respondents stated they would support the implementation of SIFs in their community (N=172; 74.5%) while 10.8% (N=25) would not and 14.7% (N=34) did not know. The majority of respondents said they would refer their patients to SIFs (N=198; 84.6%), with 4.3% (N=10) who would not and 11.1% (N=26) who were unsure., Conclusion: The findings from our study demonstrate that the majority of emergency physician respondents in Canada support the implementation of such sites (74.5%) while 84.6% of respondents would refer patients from the emergency department to such sites if they did exist. Given that many Canadian cities are actively pursuing the creation of SIFs or imminently opening such sites, it appears that our sample population of emergency physicians would both support this approach and would utilize such facilities in an effort to improve patient-centered outcomes for this often marginalized population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: We recently conducted a multicentre implementation study on the use of the Canadian C-Spine Rule (CCR) by emergency department (ED) nurses to clear the c-spine in alert and stable trauma patients (n = 4506). The objective of this study was to conduct a survey of nurses, physicians, and administrators to evaluate their views on the facilitators and barriers to the implementation of the CCR., Methods: We conducted both a paper-based and an electronic survey of the three different ED hospital staff groups of nine large teaching hospitals in Ontario, including six regional trauma centres. The content of this survey was informed by a qualitative evaluation of the opinions of the study nurses who had participated in the validation study., Results: 57.5% (281/489) ED triage nurses, 50.2% ED physicians, and 82.8% of administrators responded. Nurse responses most often showed support from manager/educators and teamwork between physicians, nurses, and managers as being important facilitators to the use of the CCR. Physician responses most often identified the importance of a nurse leader/champion/educator, and presence of strong physician leaders. Administrator responses indicated the importance of nurse educators/champions, nurse engagement, and educational support. Barriers indicated by all three groups included busy department, lack of physician support, and lack of nursing support., Conclusions: Bringing about change in clinical practice is complex. Strong leadership, effective communication, and senior physician buy-in appear to be very important. Identification of system-specific barriers and facilitators are important components of successful knowledge translation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

DNMT1 (DNA methyltransferase 1) is responsible for propagating the DNA methylation patterns during DNA replication. DNMT1 contains, in addition to a C-terminal methyltransferase domain, a large N-terminal regulatory region that is composed of an RFTS (replication foci targeting sequence) domain, a CXXC zinc finger domain and a pair of BAH (bromo adjacent homology) domains. The regulatory domains of DNMT1 mediate a network of protein-protein and protein-DNA interactions to control the recruitment and enzymatic activity of DNMT1. Here we report the crystal structure of human DNMT1 with all the structural domains (hDNMT1, residues 351-1600) in complex with S-adenosyl-l-homocysteine at 2.62Å resolution. The RFTS domain directly associates with the methyltransferase domain, thereby inhibiting the substrate binding of hDNMT1. Through structural analysis, mutational, biochemical and enzymatic studies, we further identify that a linker sequence between the CXXC and BAH1 domains, aside from its role in the CXXC domain-mediated DNMT1 autoinhibition, serves as an important regulatory element in the RFTS domain-mediated autoinhibition. In comparison with the previously determined structure of mouse DNMT1, this study also reveals a number of distinct structural features that may underlie subtle functional diversity observed for the two orthologues. In addition, this structure provides a framework for understanding the functional consequence of disease-related hDNMT1 mutations., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: There is little evidence to guide physicians on management of patients who sustain head injuries while on warfarin., Objectives: Our objective was to determine the rate of intracranial bleeding in anticoagulated patients with minor and minimal head injuries and the association with clinical features and international normalized ratio (INR)., Methods: We conducted a historical cohort study of adult patients, taking warfarin, at two tertiary care emergency departments over 2 years with minor (Glasgow Coma Score 13-15, with loss of consciousness, amnesia, or confusion) or minimal (Glasgow Coma Score 15 without loss of consciousness, amnesia, or confusion) head injuries. Patients with penetrating injuries, INR < 1.5, or a new focal neurological deficit were excluded. Our outcome, intracranial bleeding, was determined by the radiologist's final computed tomography (CT) report for imaging performed within 2 weeks., Results: There were 176 patients enrolled, of which 157 (89.2%) had CT and 28 (15.9%) had intracranial bleeding. Comparing patients with and without intracranial bleeding found no significant differences in INR, and loss of consciousness was associated with higher rate of intracranial bleeding. The rate of intracranial bleeding in the minor and minimal head injury groups was 21.9% and 4.8%, respectively., Conclusions: The rate of intracranial bleeding in patients on warfarin is considerable. Loss of consciousness is associated with high rates of intracranial bleeding. This study supports a low threshold for ordering CT scans for anticoagulated patients with head injuries., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The purpose of this study was to investigate the effect of osmotic shock and adaptation at low water activity (aw) and the type of humectant used to lower the aw, on heat resistance of three Salmonella enterica serovars (Saintpaul 02-109, Tennessee 2053H, and Elmsbuettel 1236H). The serovars were grown (adapted) or transferred (osmotic shocked) in low-aw broths and subjected to heat treatment at 55°C for up to 45 min; samples were removed at 5-min intervals and immediately placed in an ice-water bath until plating. The aw of tryptic soy broth (TSB) was lowered by the addition of 20% (wt/wt) glycerol (aw 0.94), 4% (wt/wt) sodium chloride (NaCl; aw 0.97), or 35% sucrose (wt/wt) (aw 0.95). The type of humectant and cell adaptation significantly affected the D55°C-value. Cells merely suspended in 20% glycerol broth (i.e., nonadapted) prior to heat treatment showed a larger D55°C-value (3.0 to 3.9 min), when compared with that of cells adapted in the same medium (D55°C-values of 0.86 to 0.98 min). Interestingly, cells adapted to TSB plus glycerol were not more resistant to heat than were the controls. NaCl and sucrose showed a net protective effect for all serovars under both the adapted and nonadapted conditions, with sucrose providing the most protection. Highest D55°C-values were obtained for cultures adapted to TSB plus sucrose. Based on these results, the effect of reduced aw on thermal resistance of Salmonella serovars varies greatly, depending on medium constituents and adaptation of the pathogen in these media.

Background: Little is known about the outcomes of adults with syncope seen in Canadian Emergency Departments (EDs)., Objectives: We sought to determine the frequency, timing, and type of serious adverse outcomes occurring in these patients, and the proportion that occur outside the hospital., Methods: We conducted a health records review of syncope patients presenting to a tertiary care ED over an 18-month period. We included all patients older than 16 years of age who fulfilled the syncope definition (sudden transient loss of consciousness with spontaneous complete recovery), and excluded those with altered mental status, alcohol or illicit drug use, seizure, or trauma. We assessed for outcomes in the ED and after ED disposition. We also evaluated follow-up arrangements for patients discharged from the ED., Results: Of the total 87,508 patient visits, 505 (0.6%) were due to syncope. The mean age was 58.5 years (range 16-101 years), 70.1% arrived by ambulance, and 12.3% were admitted to the hospital. Five patients died: 2 in the ED, 1 as an inpatient, and 2 after discharge. Overall, there were 49 (9.7%) serious outcomes, with dysrhythmias being the most common (4.6%); 22 (4.4%) occurred in the ED, 15 (3.0%) in the hospital, and 12 (2.4%) outside the hospital. Eight serious outcomes occurred in patients discharged from the ED without any planned follow-up., Conclusion: Although syncope represented < 1% of all patient visits, morbidity was substantial, particularly in patients discharged from the ED. Future research should help clinicians identify syncope patients at high risk for serious outcomes., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Infection of laying hens with Salmonella enterica serovar Enteritidis leads to deposition of the pathogen into the albumen or yolk of forming eggs. Heat treatment can inactivate internalized Salmonella Enteritidis in shell eggs, but factors such as the nature and location of contamination may influence the efficacy of thermal treatments. In the current research, natural contamination was mimicked by introducing small inocula of Salmonella Enteritidis into different locations of shell eggs and incubating inoculated eggs. These pathogen-containing eggs were heated at 57°C for 40 min, and temperature within eggs was monitored at the locations of inocula. Comparison of inactivation at equivalent internal temperatures revealed similar levels of lethality regardless of inoculum location. Refrigeration between incubation and heat treatment did not increase thermal resistance of cells in albumen but decreased cell inactivation in yolk. Sequential application of heat and gaseous ozone allows for the development of a process capable of decontaminating shell eggs with minimal thermal treatment and impact on egg quality. Inoculated eggs were subjected to (i) an immersion heating process similar to that used in commercial pasteurization or (ii) immersion heating, at reduced duration, followed by vacuum (50.8 kPa) and treatment with ozone gas (maximum 160 g/m(3)) under pressure (∼187.5 kPa). All treatments tested produced greater than 5-log inactivation, which is required for "pasteurization" processes. Differences were observed in the visual quality of eggs depending on treatment parameters. Application of ozone subsequent to heating allows for a significant reduction in heating time without decreasing process lethality.

A method for the simultaneous determination of two biocidal quaternary ammonium compounds; didecyldimethylammonium chloride (didecyldimethyl quat) and dodecylbenzyldimethylammonium chloride (benzyl quat), in seawater by solid phase extraction (SPE) followed by liquid chromatography-mass spectrometry (LC-MS) was developed. The optimised procedure utilised off-line extraction of the analytes from seawater using polymeric (Strata-X) SPE cartridges. Recoveries ranged from 80 to 105%, with detection limits at the low parts-per-trillion (ng/l) level for both analytes. To demonstrate sensitivity, environmental concentrations were measured at three different locations along the North East coast of England with measured values in the range 120-270ng/l., (Copyright © 2010 Elsevier B.V. All rights reserved.)

The mitogen-activated protein (MAP) kinase protein family has a critical role in cellular signaling events, with MAP kinase p38alpha acting in inflammatory processes and being an important drug discovery target. MAP kinase drug design efforts have focused on small-molecule inhibitors of the ATP catalytic site, which exhibit dose-limiting adverse effects. Therefore, characterizing other potential sites that bind substrates, inhibitors, or allosteric effectors is of great interest. Here, we present the crystal structure of human p38alpha MAP kinase, which has a lead compound bound both in the active site and in the lipid-binding site of the C-terminal cap. This C-terminal cap is formed from an extension to the kinase fold, unique to the MAP kinase and cyclin-dependent kinase families and glycogen synthase kinase 3. Binding of this lead, 4-[3-(4-fluorophenyl)-1H-pyrazol-4-yl]pyridine, to wild-type p38alpha induces movement of the C-terminal cap region, creating a hydrophobic pocket centered around residue Trp197. Computational analysis of this C-terminal domain pocket indicates notable flexibility for potentially binding different-shaped compounds, including lipids, oxidized arachidonic acid species such as leukotrienes, and small-molecule effectors. Furthermore, our structural results defining the open p38alpha C-lobe pocket provide a detailed framework for the design of novel small molecules with affinities comparable to active-site binders: to bind and potentially modulate the shape and activity of p38alpha in predetermined ways. Moreover, these results and analyses of p38alpha suggest strategies for designing specific binding compounds applicable to other MAP kinases, as well as the cyclin-dependent kinase family and glycogen synthase kinase 3beta that also utilize the C-terminal insert in their interactions.

Post-translational modification of the cell's proteome by ubiquitin and ubiquitin-like proteins provides dynamic functional regulation. Ubiquitin and SUMO are well-studied post-translational modifiers that typically impart distinct effects on their targets. The recent discovery that modification by SUMO can target proteins for ubiquitination and proteasomal degradation sets a new paradigm in the field, and offers insights into the roles of SUMO and ubiquitin in genome stability.

Background: In many patients, transient ischemic attack (TIA) precedes stroke. Prompt recognition of TIA patients who are at increased short-term risk for stroke may facilitate efficient resource utilization and improved patient outcomes. Three prognostic decision aids have been derived and validated to empower emergency physicians to stratify TIA patients for 2-day stroke risk based upon information readily available at the bedside., Clinical Question: Can a TIA stratification tool predict short-term stroke risk?, Evidence Review: Two relevant tool derivation studies and one validation study were selected from an evidence search and a structured review., Results: The three tools reveal similar prognostic capabilities, although the ABCD(2) prognostic guide may be slightly superior. A proposal scoring system for TIA patients at low risk for stroke within 90 days is presented., Conclusion: Stroke risk stratification is possible with a simple prediction rule.

The guanine nucleotide exchange factor (GEF) Vav1 plays an important role in T-cell activation and tumorigenesis. In the GEF superfamily, Vav1 has the ability to interact with multiple families of Rho GTPases. The structure of the Vav1 DH-PH-CRD/Rac1 complex to 2.6 A resolution reveals a unique intramolecular network of contacts between the Vav1 cysteine-rich domain (CRD) and the C-terminal helix of the Vav1 Dbl homology (DH) domain. These unique interactions stabilize the Vav1 DH domain for its intimate association with the Switch II region of Rac1 that is critical for the displacement of the guanine nucleotide. Small angle x-ray scattering (SAXS) studies support this domain arrangement for the complex in solution. Further, mutational analyses confirms that the atypical CRD is critical for maintaining both optimal guanine nucleotide exchange activity and broader specificity of Vav family GEFs. Taken together, the data outline the detailed nature of Vav1's ability to contact a range of Rho GTPases using a novel protein-protein interaction network.

Introduction: Traumatic injuries to the ankle/foot, knee, cervical spine, and head are very commonly seen in emergency and accident departments around the world. There has been much interest in the development of clinical decision rules to help guide the investigations of these patients in a standardised and cost-effective manner., Methods: In this article we reviewed the impact of the Ottawa ankle rules, Ottawa knee rules, Canadian C-spine rule and the Canadian CT head rule., Results: The studies conducted have confirmed that the use of well developed clinical decision rules results in less radiography, less time spent in the emergency department and does not decrease patient satisfaction or result in misdiagnosis., Conclusions: Emergency physicians around the world should adopt the use of clinical decision rules for ankle/foot, knee, cervical spine and minor head injuries. With relatively simple implementation strategies, care can be standardized and costs reduced while providing excellent clinical care.

Secondary myelodysplastic syndromes (MDS) have been reported after autologous transplantation. It is not known whether the MDS results from the pretransplant conventional-dose chemotherapy or from the high-dose chemotherapy (HDC) used for the transplant procedure. We performed a multicenter, retrospective analysis of morphologically normal pretransplant marrow or stem cell specimens from 12 patients who subsequently developed myelodysplasia after HDC. To determine if the abnormal clone was present before HDC, we used fluorescence in situ hybridization (FISH) to detect the cytogenetic markers observed at the onset of posttransplant MDS. Cryopreserved, pretransplant bone marrow, peripheral blood stem cell specimens, obtained at the time of harvest, or archival smears were used. Standard cytogenetic analysis had been performed pretransplant in four patients, showing a normal karyotype. In 9 of 12 cases, the same cytogenetic abnormality observed at the time of MDS diagnosis was detected by FISH in the pre-HDC specimens. Our findings support the hypothesis that, in many cases of posttransplant MDS, the stem cell damage results from prior conventional-dose chemotherapy and may be unrelated to HDC or the transplantation process itself.

Bone marrow transplant recipients are at risk for acquiring hepatitis C infection from the donated marrow. Twelve patients who were hepatitis C virus (HCV) RNA-negative pretransplant received marrow from anti-HCV seropositive donors. HCV RNA was present in the sera of seven of these donors. After transplant, serial serum specimens were obtained from all marrow recipients for determination of HCV RNA and aminotransferase levels. All seven recipients of marrow from HCV RNA-positive donors were HCV RNA-positive after marrow infusion; none cleared virus from the serum. All five recipients of marrow from anti-HCV seropositive, HCV RNA-negative donors remained free of HCV RNA in serum up to day 100. Abnormal serum aminotransferases were common in both HCV RNA-negative and HCV RNA-positive marrow recipients. One HCV-infected recipient developed marked elevation in aminotransferases after immunosuppressive drugs were stopped. We conclude that the presence of HCV RNA in the serum of marrow donors is an accurate predictor of HCV infection in marrow recipients. The acute infection was subclinical in all patients. The long-term risk of chronic hepatitis C virus infection in these patients remains to be determined.