Outcomes of Total Ankle Replacement Versus Ankle Arthrodesis for the Treatment of End-Stage Ankle Arthritis: A Concise Follow-up, at a Minimum of 10 Years, of a Previous Report.

Abstract: Despite the increasing utilization of total ankle replacement (TAR) for end-stage ankle arthritis, there remains a paucity of long-term follow-up data comparing arthroplasty to arthrodesis. The aim of the current paper was to provide the long-term clinical outcomes of TAR and ankle arthrodesis (AA), measured with use of validated scoring instruments, in a prospective multicenter cohort of patients with ankle arthritis. This cohort from the Canadian Orthopaedic Foot and Ankle Society (COFAS) Prospective Ankle Reconstruction Database comprised patients who underwent TAR or AA between 2001 and 2007.

Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.

Background: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide's effect on infarct volume.

Methods: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo.

Single-cell transcriptome analysis reveals CD34 as a marker of human sinoatrial node pacemaker cardiomyocytes.

The sinoatrial node regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its critical function, the cellular and molecular composition of the human sinoatrial node is not resolved.

Guidance for Canadian Breast Cancer Practice: National Consensus Recommendations for Clinical Staging of Patients Newly Diagnosed with Breast Cancer.

The accurate staging of breast cancer is fundamental for guiding treatment decisions and predicting patient outcomes. However, there can be considerable variation in routine clinical practice based on individual interpretation of guidelines and depending on the healthcare provider initially involved in working up patients newly diagnosed with breast cancer, ranging from primary care providers, triage nurses, surgeons, and/or oncologists. The optimal approach for clinical staging, particularly in asymptomatic patients presenting with intermediate-risk disease, remains a topic of dialogue among clinicians.

Catheter Ablation or Antiarrhythmic Drugs for Ventricular Tachycardia.

Background: Patients with ventricular tachycardia and ischemic cardiomyopathy are at high risk for adverse outcomes. Catheter ablation is commonly used when antiarrhythmic drugs do not suppress ventricular tachycardia. Whether catheter ablation is more effective than antiarrhythmic drugs as a first-line therapy in patients with ventricular tachycardia is uncertain.

The dichotomous roles of microbial-modified bile acids 7-oxo-DCA and isoDCA in intestinal tumorigenesis.

The gut microbiota has a significant impact on the development and function of intestinal epithelial cells (IECs) by modifying bile acid (BA) metabolites. Recently, specific gut microbiome-derived BAs, such as 7-oxo-deoxycholic acid (7-oxo-DCA) and isodeoxycholic acid (isoDCA), have been identified to be shifted inversely in colitis and hepatic liver diseases. Although the responsible gut microbes have been identified, metabolites' effects on IECs remain largely unclear.

Psilocin, the Psychoactive Metabolite of Psilocybin, Modulates Select Neuroimmune Functions of Microglial Cells in a 5-HT Receptor-Dependent Manner.

Neuroinflammation that is caused by microglia, the main immune cells of the brain, contributes to neurodegenerative diseases. Psychedelics, including psilocybin and lysergic acid diethylamide (LSD), possess certain anti-inflammatory properties and, therefore, should be considered as drug candidates for treating neuroinflammatory pathologies. When ingested, psilocybin is rapidly dephosphorylated to yield psilocin, which crosses the blood-brain barrier and exerts psychotropic activity by interacting with the 5-hydroxytryptamine 2A receptors (5-HTRs) on neurons.

Polygenic and transcriptional risk scores identify chronic obstructive pulmonary disease subtypes in the COPDGene and ECLIPSE cohort studies.

Background: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics.

Methods: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets.

Side effect management algorithms for niraparib/abiraterone acetate in prostate cancer.

Introduction: Niraparib, a PARP1/2 inhibitor, is newly approved in combination with abiraterone acetate (AA) plus prednisone or prednisolone (niraparib/AA+P) for the treatment of adult patients with BRCA-mutated, treatment-naïve metastatic castration resistant prostate cancer (mCRPC). Detailed guidance beyond the prescribing information may be helpful in managing the side effect profile and dosing practicalities of this combination therapy.

Materials And Methods: A panel of specialists convened to design management algorithms for four common niraparib/AA+P treatment-related adverse events (AEs) in mCRPC; anemia, thrombocytopenia, hypertension, and nausea.

In-person vs mobile app facilitated life skills education to improve the mental health of internally displaced persons in Nigeria: protocol for the RESETTLE-IDPs cluster randomized hybrid type 2 effectiveness-implementation trial.

Background: Internally displaced persons (IDPs) in Nigeria face a high burden of mental health disorders, with limited access to evidence-based, culturally relevant interventions. Life skills education (LSE) is a promising approach to promote mental health and psychosocial well-being in humanitarian settings. This study aims to evaluate the effectiveness and implementation of a culturally adapted LSE program delivered through in-person and mobile platforms among IDPs in Northern Nigeria.

Emerging interactions between RNA methylation and chromatin architecture.

Epitranscriptomics, the study of chemical modifications of RNA molecules, is increasingly recognized as an important component of gene expression regulation. While the majority of research has focused on N-methyladenosine (mA) RNA methylation on mRNAs, emerging evidence has revealed that the mA modification extends beyond mRNAs to include chromatin-associated RNAs (caRNAs). CaRNAs constitute an important class of RNAs characterized by their interaction with the genome and epigenome.

Protein requirements in adults with phenylketonuria and bioavailability of glycomacropeptide compared to an l-amino acid-based product.

Background: Phenylketonuria (PKU) is caused by phenylalanine hydroxylase deficiency. Treatment is primarily a low-Phe diet combined with l-amino acid-based products (l-AA). Protein requirements in adults with PKU have not been directly determined.

Transient CAR T cells with specificity to oncofetal glycosaminoglycans in solid tumors.

Glycosaminoglycans are often deprioritized as targets for synthetic immunotherapy due to the complexity of glyco-epitopes and limited options for obtaining specific subtype binding. Solid tumors express proteoglycans that are modified with oncofetal chondroitin sulfate (CS), a modification normally restricted to the placenta. Here, we report the design and functionality of transient chimeric antigen receptor (CAR) T cells with selectivity to oncofetal CS.

(Mis)Alignment in resident and advisor co-regulated learning in competency-based training.

Background/objective: In implementing competence-based medical education (CBME), some Canadian residency programmes recruit clinicians to function as Academic Advisors (AAs). AAs are expected to help monitor residents' progress, coach them longitudinally, and serve as sources of co-regulated learning (Co-RL) to support their developing self-regulated learning (SRL) abilities. Implementing the AA role is optional, meaning each residency programme must decide whether and how to implement it, which could generate uncertainty and heterogeneity in how effectively AAs will "monitor and advise" residents.

Prodrug Nanomedicine for Synovium Targeted Therapy of Inflammatory Arthritis: Insights from Animal Model and Human Synovial Joint Fluid.

Many patients cannot tolerate low-dose weekly methotrexate (MTX) therapy for inflammatory arthritis treatment due to life-threatening toxicity. Although biologics offer a target-specific therapy, it raises the risk of serious infections and even cancer due to immune system suppression. We introduce an anti-inflammatory arthritis MTX ester prodrug using a long-circulating biocompatible polymeric macromolecule: folic acid (FA) functionalized hyperbranched polyglycerol (HPG).

Interfacial modulation of TiCT MXene using functionalized cellulose nanofibrils for enhanced electrochemical actuation.

Electrochemical actuators (ECAs) with low voltage actuation and large deformation ranges generally require electrode materials with high ion kinetic energy transport, high charge storage, and excellent electrochemical-mechanical properties. However, the fabrication of such actuators remains a major challenge. In the present work, hybrid electroactive films were fabricated by self-assembling one-dimensional functionalized cellulose nanofibrils (CNFs) with two-dimensional MXene (TiCT).