Pharmacological inhibition of ezrin reduces proliferative and invasive phenotype in acute lymphoblastic leukemia cells.

Ezrin (EZR) is an actin-associated protein that is often upregulated in cancers. Here we investigate the role of EZR in acute lymphoblastic leukemia (ALL) and explore the therapeutic potential of a pharmacological EZR inhibitor, NSC305787. ALL patient cohorts exhibit significantly elevated EZR mRNA levels, indicating its association with the malignant phenotype.

Which adults aged 65 and older are at low-risk for cervical spine injuries after low-level falls?

Objectives: The population is aging and falls are a common reason for emergency department visits. Appropriate imaging in this population is important. The objectives of this study were to estimate the prevalence of cervical spine injury and identify factors associated with cervical spine injuries in adults ≥ 65 years after low-level falls.

Implementation, Clinical Benefit and Safety of a D-Dimer-Focused Pulmonary Embolism Testing Pathway in the Emergency Department.

Study Objective: Computed tomography pulmonary angiogram (CTPA) is overused during pulmonary embolism (PE) testing in the emergency department (ED), whereas prediction rules and D-dimer are underused. We report the adherence, clinical benefit, and safety of a D-dimer-only strategy to guide need for PE imaging in the ED.

Methods: This was a prospective multicenter implementation study in 2 EDs with historical and external controls.

Emergency physician gender and head computed tomography orders for older adults who have fallen.

Objective: Physicians vary in their computed tomography (CT) scan usage. It remains unclear how physician gender relates to clinical practice or patient outcomes. The aim of this study was to assess the association between physician gender and decision to order head CT scans for older emergency patients who had fallen.

A Longitudinal Survey on Canadian Emergency Physician Burnout.

Study Objective: Since Canada eased pandemic restrictions, emergency departments have experienced record levels of patient attendance, wait times, bed blocking, and crowding. The aim of this study was to report Canadian emergency physician burnout rates compared with the same physicians in 2020 and to describe how emergency medicine work has affected emergency physician well-being.

Methods: This longitudinal study on Canadian emergency physician wellness enrolled participants in April 2020.

RhoU forms homo-oligomers to regulate cellular responses.

RhoU is an atypical member of the Rho family of small G-proteins, which has N- and C-terminal extensions compared to the classic Rho GTPases RhoA, Rac1 and Cdc42, and associates with membranes through C-terminal palmitoylation rather than prenylation. RhoU mRNA expression is upregulated in prostate cancer and is considered a marker for disease progression. Here, we show that RhoU overexpression in prostate cancer cells increases cell migration and invasion.

Derivation of the Falls Decision Rule to exclude intracranial bleeding without head CT in older adults who have fallen.

Background: Ground-level falls are common among older adults and are the most frequent cause of traumatic intracranial bleeding. The aim of this study was to derive a clinical decision rule that safely excludes clinically important intracranial bleeding in older adults who present to the emergency department after a fall, without the need for a computed tomography (CT) scan of the head.

Methods: This prospective cohort study in 11 emergency departments in Canada and the United States enrolled patients aged 65 years or older who presented after falling from standing on level ground, off a chair or toilet seat, or out of bed.

Was Virtual Care as Safe as In-Person Care? Analyzing Patient Outcomes at Seven and Thirty Days in Ontario during the COVID-19 Pandemic.

In 2020, almost overnight, the paradigm for healthcare interactions changed in Ontario. To limit person-to-person transmission of COVID-19, the norm of in-person interactions shifted to virtual care. While this shift was part of broader public health measures and an acknowledgment of patient and societal concerns, it also represented a change in care modalities that had the potential to affect the quality of care provided, as well as short- and long-term patient outcomes.

Anticoagulation prescription among atrial fibrillation patients managed with and without an anticoagulant initiation pathway: a cohort study.

Background And Importance: The Canadian Association of Emergency Physicians atrial fibrillation (AF) checklist advises that emergency physicians initiate anticoagulation therapy for patients with AF or flutter who are CHADS65 positive.

Objectives: The aim was to compare anticoagulation initiation rates between patients treated with and without an anticoagulation assessment pathway (the SAFE pathway).

Design: This was a retrospective cohort study.

Absence of Increased Susceptibility to Acetaminophen-Induced Liver Injury in a Diet-Induced NAFLD Mouse Model.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease and its influence on drug-induced liver injury (DILI) is not fully understood. We investigated whether NAFLD can influence acetaminophen (APAP [N-acetyl-p-aminophenol])-induced hepatotoxicity in a diet-induced obese (DIO) mouse model of NAFLD. The male C57BL/6NTac DIO mice, fed a high-fat diet for more than 12 weeks, developed obesity, hyperinsulinemia, impaired glucose tolerance, and hepatomegaly with hepatic steatosis, similar to human NAFLD.

HDAC Inhibition Restores Response to HER2-Targeted Therapy in Breast Cancer via Induction.

The downregulation of Pleckstrin Homology-Like Domain family A member 1 (PHLDA1) expression mediates resistance to targeted therapies in receptor tyrosine kinase-driven cancers. The restoration and maintenance of PHLDA1 levels in cancer cells thus constitutes a potential strategy to circumvent resistance to inhibitors of receptor tyrosine kinases. Through a pharmacological approach, we identify the inhibition of MAPK signalling as a crucial step in downregulation.

Statins change the cytokine profile in -infected U937 macrophages and murine cardiac tissue through Rho-associated kinases inhibition.

Introduction: Chronic Chagasic cardiomyopathy (CCC), caused by the protozoan Trypanosoma cruzi, is the most severe manifestation of Chagas disease.CCC is characterized by cardiac inflammation and fibrosis caused by a persistent inflammatory response. Following infection, macrophages secrete inflammatory mediators such as IL-1β, IL-6, and TNF-α to control parasitemia.

Comparison of YEARS and Adjust-Unlikely D-dimer Testing for Pulmonary Embolism in the Emergency Department.

Study Objective: We prospectively assessed the diagnostic accuracy of YEARS and a modified age-adjusted clinical decision rule ("Adjust-Unlikely") for pulmonary embolism (PE) testing in the emergency department.

Methods: This study was conducted in tertiary care Canadian emergency departments. When the D-dimer was <500 ng/ml, PE was excluded.

Humans not heroes: Canadian emergency physician experiences during the early COVID-19 pandemic.

Background: The pandemic has upended much clinical care, irrevocably changing our health systems and thrusting emergency physicians into a time of great uncertainty and change. This study is a follow-up to a survey that examined the early pandemic experience among Canadian emergency physicians and aimed to qualitatively describe the experiences of these physicians during the global pandemic. The study was conducted at a time when Canadian COVID-19 case numbers were low.

Assembly of nuclear dimers of PI3K regulatory subunits is regulated by the Cdc42-activated tyrosine kinase ACK.

Activated Cdc42-associated kinase (ACK) is an oncogenic nonreceptor tyrosine kinase associated with poor prognosis in several human cancers. ACK promotes proliferation, in part by contributing to the activation of Akt, the major effector of class 1A phosphoinositide 3-kinases (PI3Ks), which transduce signals via membrane phosphoinositol lipids. We now show that ACK also interacts with other key components of class 1A PI3K signaling, the PI3K regulatory subunits.

Short-term tetrabromobisphenol A exposure promotes fibrosis of human uterine fibroid cells in a 3D culture system through TGF-beta signaling.

Tetrabromobisphenol A (TBBPA), a derivative of BPA, is a ubiquitous environmental contaminant with weak estrogenic properties. In women, uterine fibroids are highly prevalent estrogen-responsive tumors often with excessive accumulation of extracellular matrix (ECM) and may be the target of environmental estrogens. We have found that BPA has profibrotic effects in vitro, in addition to previous reports of the in vivo fibrotic effects of BPA in mouse uterus.

Diagnostic Performance of Serial High-Sensitivity Cardiac Troponin Measurements in the Emergency Setting.

Serial high-sensitivity cardiac troponin (hsTn) testing in the emergency department (ED) and the intensive cardiac care unit may assist physicians in ruling out or ruling in acute myocardial infarction (MI). There are three major algorithms proposed for high-sensitivity cardiac troponin I (hsTnI) using serial measurements while incorporating absolute concentration changes for MI or death following ED presentation. We sought to determine the diagnostic estimates of these three algorithms and if one was superior in two different Canadian ED patient cohorts with serial hsTnI measurements.

Which older emergency patients are at risk of intracranial bleeding after a fall? A protocol to derive a clinical decision rule for the emergency department.

Introduction: Falling on level ground is now the most common cause of traumatic intracranial bleeding worldwide. Older adults frequently present to the emergency department (ED) after falling. It can be challenging for clinicians to determine who requires brain imaging to rule out traumatic intracranial bleeding, and often head injury decision rules do not apply to older adults who fall.

Reliability of patient-reported outcome measures: Hemorrhage, anticoagulant, antiplatelet medication use.

Background: Most antithrombotic medication users are older adults. Patient-reported outcome measures are commonly used in clinical research on antithrombotic medication, such as the diagnosis of intracranial hemorrhage.

Objectives: To determine the reliability of patient-reported intracranial hemorrhage, anticoagulant and platelet aggregation inhibitor use in the older adult population.

Anticoagulation for newly diagnosed atrial fibrillation and 90-day rates of stroke and bleeding.

Background: Atrial fibrillation increases the risk of stroke, which can be mitigated by anticoagulant prescription. We evaluated local emergency physician anticoagulation practice for patients discharged from the emergency department with atrial fibrillation, along with 90-day incidence of stroke and major bleeding.

Methods: This was a health record review of patients diagnosed with new onset atrial fibrillation in two emergency departments between 2014 and 2017.

Feasibility of a quality improvement project to increase adherence to evidence-based pulmonary embolism diagnosis in the emergency department.

Background: Many evidence-based clinical decision tools are available for the diagnosis of pulmonary embolism (PE). However, these clinical decision tools have had suboptimal uptake in the everyday clinical practice in emergency departments (EDs), despite numerous implementation efforts. We aimed to test the feasibility of a multi-faceted intervention to implement an evidence-based PE diagnosis protocol.

Using the clinical chemistry score in the emergency department to detect adverse cardiac events: a diagnostic accuracy study.

Background: The ability to rule out or in a major adverse cardiac event (MACE) in patients with suspected acute coronary syndrome at emergency department (ED) presentation would be beneficial to patient care and the health care system. The clinical chemistry score (CCS) was evaluated in this context.

Methods: This diagnostic accuracy study evaluated 2 different ED cohorts with suspected acute coronary syndrome.

Canadian emergency physician psychological distress and burnout during the first 10 weeks of COVID-19: A mixed-methods study.

Objectives: The aim of this study was to report burnout time trends and describe the psychological effects of working as a Canadian emergency physician during the first weeks of the coronavirus disease 2019 (COVID-19) pandemic.

Methods: This was a mixed-methods study. Emergency physicians completed a weekly online survey.