A systematic review and meta-analysis of the effect of routine early angiography in patients with return of spontaneous circulation after Out-of-Hospital Cardiac Arrest.

Background: Early coronary angiography (CAG) has been reported in individual studies and systematic reviews to significantly improve outcomes of patients with return of spontaneous circulation (ROSC) after cardiac arrest (CA).

Methods: We undertook a systematic review and meta-analysis to evaluate the impact of early CAG on key clinical outcomes in comatose patients after ROSC following out-of-hospital CA of presumed cardiac origin. We searched the PubMED, EMBASE, CINAHL, ERIC and Cochrane Central Register of Controlled Trials databases from 1990 until April 2020.

Outcomes of out of hospital cardiac arrest in First Nations and non-First Nations patients in Saskatoon.

Introduction: One in nine (11.7%) people in Saskatchewan identify as First Nations. It is known that First Nations people have a higher burden of cardiovascular disease, but not whether outcomes of out of hospital cardiac arrest are different.

Regulation of epithelial-mesenchymal transition and organoid morphogenesis by a novel TGFβ-TCF7L2 isoform-specific signaling pathway.

Alternative splicing contributes to diversification of gene function, yet consequences of splicing on functions of specific gene products is poorly understood. The major transcription factor TCF7L2 undergoes alternative splicing but the biological significance of TCF7L2 isoforms has remained largely to be elucidated. Here, we find that the TCF7L2 E-isoforms maintain, whereas the M and S isoforms disrupt morphogenesis of 3D-epithelial cell-derived organoids via regulation of epithelial-mesenchymal transition (EMT).

Impact of Pit-Crew Cardiopulmonary Resuscitation on Out-of-Hospital Cardiac Arrest in Saskatoon.

Background: In the prehospital setting, pit-crew models of cardiopulmonary resuscitation (CPR) have shown improvements in survival after out-of-hospital cardiac arrest (OHCA). Certain districts in North America have adopted this model, including Saskatoon, Saskatchewan, Canada.

Objectives: Our objectives were to determine whether pit-crew CPR has an impact on survival to discharge after OHCA in Saskatoon, Canada.

Emergency department referrals from a provincial medical call centre: Is it more than just 1-800-go-to-emerg?

Objective: HealthLine is Saskatchewan's provincial 24-hour health information and support telephone line. A proportion of HealthLine's callers are referred to the emergency department (ED) for further assessment. The purpose of this study was to gain insight into the appropriateness of these referrals and assess whether they increased the burden on an already strained ED system.

Diagnostic accuracy of eFAST in the trauma patient: a systematic review and meta-analysis.

Objectives: Performing an extended Focused Assessment with Sonography in Trauma (eFAST) exam is common practice in the initial assessment of trauma patients. The objective of this study was to systematically review the published literature on diagnostic accuracy of all components of the eFAST exam.

Methods: We searched Medline and Embase from inception through October 2018, for diagnostic studies examining the sensitivity and specificity of the eFAST exam.

Evaluation of emergency department ultrasound machines for the presence of occult blood.

Objectives: Bedside ultrasound in the emergency department is a common diagnostic tool, especially when evaluating trauma patients. Many trauma patients have blood on their chest and abdomen that may contact the probe during examination. The primary aim of this study was to investigate whether occult blood contamination was present on the emergency department ultrasound machine, both after daily use and after use in trauma.

A novel role for the SUMO E3 ligase PIAS1 in cancer metastasis.

Tumor metastasis contributes to the grave morbidity and mortality of cancer, but the mechanisms underlying tumor cell invasiveness and metastasis remain incompletely understood. Here, we report that expression of the SUMO E3 ligase PIAS1 suppresses TGFβ-induced activation of the matrix metalloproteinase MMP2 in human breast cancer cells. We also find that knockdown of endogenous PIAS1 or inhibition of its SUMO E3 ligase activity stimulates the ability of TGFβ to induce an aggressive phenotype in three-dimensional breast cancer cell organoids.

Computerized physician order entry and decision support improves ED analgesic ordering for renal colic.

Objectives: Computerized physician order entry (CPOE) offers the potential for safer, faster patient care, as well as greater use of evidence-based therapy via built-in decision support. However, the effectiveness of CPOE in yielding these benefits has shown mixed results in the emergency department (ED) setting. Our objective was to evaluate the impact of CPOE implementation on analgesic prescribing and dosing practices for renal colic presentations.

Outcomes of children with suspected appendicitis and incompletely visualized appendix on ultrasound.

Objectives: The objective was to review the clinical outcomes of children with suspected appendicitis after an ultrasound (US) examination fails to fully visualize the appendix, the diagnostic characteristics of US in children with suspected appendicitis, and the predictive value of secondary signs of appendicitis when the appendix is not fully visualized.

Methods: This was a retrospective health record review of children aged 3 to 17 years presenting to a tertiary pediatric emergency department (ED) with suspected appendicitis. Descriptive statistics and diagnostic test characteristics are reported.

Identification of a novel function for the chromatin remodeling protein ING2 in muscle differentiation.

The inhibitor of growth (ING) family of zinc-finger plant homeodomain (PHD)-containing chromatin remodeling protein controls gene expression and has been implicated in the regulation of cell proliferation and death. However, the role of ING proteins in cell differentiation remains largely unexplored. Here, we identify an essential function for ING2 in muscle differentiation.

An isoform-specific SnoN1-FOXO1 repressor complex controls neuronal morphogenesis and positioning in the mammalian brain.

Control of neuronal positioning is fundamental to normal brain development. However, the cell-intrinsic mechanisms that govern neuronal positioning remain to be elucidated. Here, we report that the spliced protein products of the transcriptional regulator SnoN, SnoN1 and SnoN2, harbor opposing functions in the coordinate regulation of neuronal branching and positioning.

Suppression of TGFβ-induced epithelial-mesenchymal transition like phenotype by a PIAS1 regulated sumoylation pathway in NMuMG epithelial cells.

Epithelial-mesenchymal-transition (EMT) is a fundamental cellular process that is critical for normal development and tumor metastasis. The transforming growth factor beta (TGFβ) is a potent inducer of EMT like effects, but the mechanisms that regulate TGFβ-induced EMT remain incompletely understood. Using the widely employed NMuMG mammary epithelial cells as a model to study TGFβ-induced EMT, we report that TGFβ downregulates the levels of the SUMO E3 ligase PIAS1 in cells undergoing EMT.

Cyclic AMP phosphodiesterase 4D (PDE4D) Tethers EPAC1 in a vascular endothelial cadherin (VE-Cad)-based signaling complex and controls cAMP-mediated vascular permeability.

Vascular endothelial cell (VEC) permeability is largely dependent on the integrity of vascular endothelial cadherin (VE-cadherin or VE-Cad)-based intercellular adhesions. Activators of protein kinase A (PKA) or of exchange protein activated by cAMP (EPAC) reduce VEC permeability largely by stabilizing VE-Cad-based intercellular adhesions. Currently, little is known concerning the nature and composition of the signaling complexes that allow PKA or EPAC to regulate VE-Cad-based structures and through these actions control permeability.

A SnoN-Ccd1 pathway promotes axonal morphogenesis in the mammalian brain.

The transcriptional corepressor SnoN is a critical regulator of axonal morphogenesis, but how SnoN drives axonal growth is unknown. Here, we report that gene-profiling analyses in cerebellar granule neurons reveal that the large majority of genes altered upon SnoN knockdown are surprisingly downregulated, suggesting that SnoN may activate transcription in neurons. Accordingly, we find that the transcriptional coactivator p300 interacts with SnoN, and p300 plays a critical role in SnoN-induced axon growth.

ING2 as a novel mediator of transforming growth factor-beta-dependent responses in epithelial cells.

Members of the ING (inhibitor of growth) family of chromatin modifying proteins (ING1-ING5) have emerged as critical regulators of gene expression and cellular responses, suggesting that the ING proteins may impinge on specific signal transduction pathways and their mediated effects. Here, we demonstrate a role for the protein ING2 in mediating responses by the transforming growth factor (TGF)-beta-Smad signaling pathway. We show that ING2 promotes TGF-beta-induced transcription.

Both protein kinase A and exchange protein activated by cAMP coordinate adhesion of human vascular endothelial cells.

cAMP regulates integrin-dependent adhesions of vascular endothelial cells (VECs) to extracellular matrix proteins, their vascular endothelial cadherin-dependent intercellular adhesions, and their proliferation and migration in response to growth and chemotactic factors. Previously, we reported that cAMP-elevating agents differentially inhibited migration of human VECs isolated from large vascular structures (macro-VECs, human aortic endothelial cells [HAECs]) or small vascular structures (micro-VECs, human microvascular endothelial cells [HMVECs]) and that cAMP hydrolysis by phosphodiesterase (PDE)3 and PDE4 enzymes was important in coordinating this difference. Here we report that 2 cAMP-effector enzymes, namely protein kinase (PK)A and exchange protein activated by cAMP (EPAC), each regulate extracellular matrix protein-based adhesions of both macro- and micro-VECs.

Adiponectin, ghrelin, and leptin differentially influence human platelet and human vascular endothelial cell functions: implication in obesity-associated cardiovascular diseases.

A very strong epidemiological link exists between obesity, the metabolic syndrome, diabetes and diabetes-associated cardiovascular pathologies. For this reason the peripheral effects of the centrally-acting satiety adipokines, adiponectin and leptin, and of non-adipose-derived hormones with similar effects, like ghrelin, have received considerable attention. In this report, we have extended our previous studies of the pro-thrombotic effects of leptin and determined the effects of adiponectin or ghrelin on human platelet activation.

Sumoylated SnoN represses transcription in a promoter-specific manner.

The transcriptional modulator SnoN controls a diverse set of biological processes, including cell proliferation and differentiation. The mechanisms by which SnoN regulates these processes remain incompletely understood. Recent studies have shown that SnoN exerts positive or negative regulatory effects on transcription.

Vascular endothelial cell cyclic nucleotide phosphodiesterases and regulated cell migration: implications in angiogenesis.

Angiogenesis is necessary during embryonic development and wound healing but can be detrimental in pathologies, including cancer. Because initiation of angiogenesis involves migration and proliferation of vascular endothelial cells (VECs) and cAMP-elevating agents inhibit these events, such agents may represent a novel therapeutic avenue to controlling angiogenesis. Intracellular cAMP levels are regulated by their synthesis by adenylyl cyclases and hydrolysis by cyclic nucleotide phosphodiesterases (PDEs).

Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system.

Cyclic AMP (cAMP) and cGMP regulate a myriad of cellular functions, such as metabolism, contractility, motility, and transcription in virtually all cell types, including those of the cardiovascular system. Considerable effort over the last 20 years has allowed identification of the cellular components involved in the synthesis of cyclic nucleotides, as well as effectors of cyclic nucleotide-mediated signaling. More recently, a central role for cyclic nucleotide phosphodiesterase (PDE) has also been elaborated in many cell types, including those involved in regulating the activities of the cardiovascular system.

Altered phosphodiesterase 3-mediated cAMP hydrolysis contributes to a hypermotile phenotype in obese JCR:LA-cp rat aortic vascular smooth muscle cells: implications for diabetes-associated cardiovascular disease.

Cardiovascular diseases represent a significant cause of morbidity and mortality in diabetes. Of the many animal models used in the study of non-insulin-dependent (type 2) diabetes, the JCR:LA-cp rat is unique in that it develops insulin resistance in the presence of obesity and manifests both peripheral and coronary vasculopathies. In this animal model, arterial vascular smooth muscle cells (VSMCs) from homozygous obese (cp/cp) rats, but not from age-matched healthy (+/+ or + /cp, collectively defined +/?) littermates, display an " activated" phenotype in vitro and in vivo and have an elevated level of cAMP phosphodiesterase (PDE) activity.