Factors Influencing the Timeliness and Completeness of Appropriate Staging Investigations for Patients with Stage I-III Lung Cancer in Southeastern Ontario.

(1) Background: Comprehensive and timely lung cancer (LC) staging is essential for prognosis and management. The Lung Diagnostic Assessment Program (LDAP) in Southeastern (SE) Ontario aims to provide rapid, guideline-concordant care for suspected LC patients. We evaluated factors affecting the completeness and timeliness of staging for stage I-III LC patients in SE Ontario, including the impact of LDAP management.

Optimized protocol for in vivo affinity purification proteomics and biochemistry using C. elegans.

We present an optimized protocol for in vivo affinity purification proteomics and biochemistry using the model organism C. elegans. We describe steps for target tagging, large-scale culture, affinity purification using a cryomill, mass spectrometry and validation of candidate binding proteins.

Influence of a patient navigation program on timeliness of care in patients with esophageal cancer.

Background: Patient navigation (P.N.) is designed to eliminate barriers to care.

Loss-of-function variants in MYCBP2 cause neurobehavioural phenotypes and corpus callosum defects.

The corpus callosum is a bundle of axon fibres that connects the two hemispheres of the brain. Neurodevelopmental disorders that feature dysgenesis of the corpus callosum as a core phenotype offer a valuable window into pathology derived from abnormal axon development. Here, we describe a cohort of eight patients with a neurodevelopmental disorder characterized by a range of deficits including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy and autistic features.

Ptchd1 mediates opioid tolerance via cholesterol-dependent effects on μ-opioid receptor trafficking.

Repeated exposure to opioids causes tolerance, which limits their analgesic utility and contributes to overdose and abuse liability. However, the molecular mechanisms underpinning tolerance are not well understood. Here, we used a forward genetic screen in Caenorhabditis elegans for unbiased identification of genes regulating opioid tolerance which revealed a role for PTR-25/Ptchd1.

Assessment and treatment of depression in people with multiple sclerosis: A qualitative analysis of specialist clinicians' experiences.

Background: Depression is common in people with multiple sclerosis (MS), with lifetime prevalence estimates between 25 and 50%. Depression is commonly underdiagnosed and undertreated in people with MS. This qualitative study assessed current practices, as well as facilitators and required resources to improve detection and management of depression in people with MS.

O-GlcNAc transferase OGT-1 and the ubiquitin ligase EEL-1 modulate seizure susceptibility in C. elegans.

Neurodevelopmental disorders such as epilepsy and autism have been linked to an imbalance of excitation and inhibition (E/I) in the central nervous system. The simplicity and tractability of C. elegans allows our electroconvulsive seizure (ES) assay to be used as a behavioral readout of the locomotor circuit and neuronal function.

Genetic modeling of GNAO1 disorder delineates mechanisms of Gαo dysfunction.

GNAO1 encephalopathy is a neurodevelopmental disorder with a spectrum of symptoms that include dystonic movements, seizures and developmental delay. While numerous GNAO1 mutations are associated with this disorder, the functional consequences of pathological variants are not completely understood. Here, we deployed the invertebrate C.

Ingested removable partial denture causing esophageal perforation in a patient with autism: Management and prevention.

A 60-year-old woman with autism and a repetitive swallowing behavior ingested a removable partial denture that impacted in the proximal esophagus. Attempts at endoscopic removal were unsuccessful. Esophageal perforation was recognized, necessitating emergency transcervical surgical exploration, esophagotomy with foreign body removal, and repair of the esophageal perforation.

Impact of the acute care surgery model on resident operative experience in emergency general surgery.

Background: The acute care surgery (ACS) model has been shown to improve patient, hospital and surgeon-specific outcomes. To date, however, little has been published on its impact on residency training. Our study compared the emergency general surgery (EGS) operative experiences of residents assigned to ACS versus elective surgical rotations.

Lung Resection Without Tissue Diagnosis: A Pragmatic Perspective on the Indeterminate Pulmonary Nodule.

Background: The indeterminate pulmonary nodule is a common clinical problem. Preoperative tissue diagnosis is not always possible, despite all attempts. The objectives of this study were to determine the frequency of a malignant diagnosis in this scenario and whether attempted preoperative biopsy impacted estimation of the risk of malignancy.

Operative timing is associated with increased morbidity and mortality in patients undergoing emergency general surgery: a multisite study of emergency general services in a single academic network.

Background: Despite the widespread implementation of the acute care surgery (ACS) model, limited access to operating room time represents a barrier to the optimal delivery of emergency general surgery (EGS) care. The objective of this study was to describe the effect of operative timing on outcomes in EGS in a network of teaching hospitals.

Methods: We conducted a retrospective review of EGS operations performed at 3 teaching hospitals in a single academic network.

Diagnosis and management of acute cholecystitis: a single-centre audit of guideline adherence and patient outcomes.

Background: The Tokyo Guidelines were published in 2007 and updated in 2013 and 2018, with recommendations for the diagnosis and management of acute cholecystitis. We assessed guideline adherence at our academic centre and its impact on patient outcomes.

Methods: This is a retrospective chart review of patients with acute calculous cholecystitis who underwent cholecystectomy at our institution between November 2013 and March 2015.

Roles of the HUWE1 ubiquitin ligase in nervous system development, function and disease.

Huwe1 is a highly conserved member of the HECT E3 ubiquitin ligase family. Here, we explore the growing importance of Huwe1 in nervous system development, function and disease. We discuss extensive progress made in deciphering how Huwe1 regulates neural progenitor proliferation and differentiation, cell migration, and axon development.

Context-dependent operation of neural circuits underlies a navigation behavior in .

The nervous system evaluates environmental cues and adjusts motor output to ensure navigation toward a preferred environment. The nematode navigates in the thermal environment and migrates toward its cultivation temperature by moving up or down thermal gradients depending not only on absolute temperature but on relative difference between current and previously experienced cultivation temperature. Although previous studies showed that such thermal context-dependent opposing migration is mediated by bias in frequency and direction of reorientation behavior, the complete neural pathways-from sensory to motor neurons-and their circuit logics underlying the opposing behavioral bias remain elusive.

Autophagy is inhibited by ubiquitin ligase activity in the nervous system.

Autophagy is an intracellular catabolic process prominent in starvation, aging and disease. Neuronal autophagy is particularly important, as it affects the development and function of the nervous system, and is heavily implicated in neurodegenerative disease. Nonetheless, how autophagy is regulated in neurons remains poorly understood.