Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra-Articular Space.

Intra-articular glucocorticoid injections are effective in controlling inflammation and pain in arthritides but restricted by short duration of action and risk of joint degeneration. Controlled drug release using biocompatible hydrogels offers a unique solution, but limitations of in situ gelation restrict their application. Gellan sheared hydrogels (GSHs) retain the advantages of hydrogels, however their unique microstructures lend themselves to intra-articular application - capable of shear thinning under force but restructuring at rest to enhance residence.

Organ-on-a-chip for studying immune cell adhesion to liver sinusoidal endothelial cells: the potential for testing immunotherapies and cell therapy trafficking.

Immunotherapy has changed the landscape of treatment options for patients with hepatocellular cancer. Checkpoint inhibitors are now standard of care for patients with advanced tumours, yet the majority remain resistant to this therapy and urgent approaches are needed to boost the efficacy of these agents. Targeting the liver endothelial cells, as the orchestrators of immune cell recruitment, within the tumour microenvironment of this highly vascular cancer could potentially boost immune cell infiltration.

Expression of E-cadherin by CD8 T cells promotes their invasion into biliary epithelial cells.

The presence of CD8 T cells in the cytoplasm of biliary epithelial cells (BEC) has been correlated with biliary damage associated with primary biliary cholangitis (PBC). Here, we characterise the mechanism of CD8 T cell invasion into BEC. CD8 T cells observed within BEC were large, eccentric, and expressed E-cadherin, CD103 and CD69.

Corticosterone and immune responses to dehydration in squamate reptiles.

Many environments present some degree of seasonal water limitations; organisms that live in such environments must be adapted to survive periods without permanent water access. Often this involves the ability to tolerate dehydration, which can have adverse physiological effects and is typically considered a physiological stressor. While having many functions, the hormone corticosterone (CORT) is often released in response to stressors, yet increasing plasma CORT while dehydrated could be considered maladaptive, especially for species that experience predictable bouts of dehydration and have related coping mechanisms.

Urban and rural male song sparrows (Melospiza melodia) differ in territorial aggression and activation of vasotocin neurons in response to song challenge.

When living in urban habitats, 'urban adapter' species often show greater aggression toward conspecifics, yet we do not understand the mechanisms underlying this behavioral shift. The neuroendocrine system regulates socio-sexual behaviors including aggression and thus could mediate behavioral responses to urbanization. Indeed, urban male song sparrows (Melospiza melodia), which are more territorially aggressive, also have greater abundance of the neuropeptide arginine vasotocin (AVT) in nodes of the brain social behavior network.

Student achievement trajectories in Ontario: Creating and validating a province-wide, multi-cohort and longitudinal database.

Introduction: Longitudinal data that tracks student achievement over many years are crucial for understanding children's learning and for guiding effective policies and interventions. Despite being Canada's most populous province, Ontario lacks such large-scale and longitudinal data on student learning. Linking datasets across cohorts requires rigorous linkage protocols, flexible handling of complex cohort structures, methods to validate linked datasets, and viable organizational partnerships.

Spontaneous Intracranial Hypotension: An Uncommon Cause of Postural Vestibulocochlear Symptoms.

Spontaneous intracranial hypotension is an uncommon but increasingly recognized condition characterized by an orthostatic headache secondary to low cerebrospinal fluid pressure. Vestibulocochlear symptoms are common but rarely the only presenting feature and can be challenging to differentiate from Meniere's disease. We present a case series that highlights the common vestibulocochlear symptoms and a review of the literature to increase awareness amongst otolaryngologists and highlight the path to diagnosis and management of this condition.

Non-native grazers affect physiological and demographic responses of greater sage-grouse.

Non-native ungulate grazing has negatively impacted native species across the globe, leading to massive loss of biodiversity and ecosystem services. Despite their pervasiveness, interactions between non-native grazers and native species are not fully understood. We often observe declines in demography or survival of these native species, but lack understanding about the mechanisms underlying these declines.

The Role of B Cells in Adult and Paediatric Liver Injury.

B lymphocytes are multitasking cells that direct the immune response by producing pro- or anti-inflammatory cytokines, by presenting processed antigen for T cell activation and co-stimulation, and by turning into antibody-secreting cells. These functions are important to control infection in the liver but can also exacerbate tissue damage and fibrosis as part of persistent inflammation that can lead to end stage disease requiring a transplant. In transplantation, immunosuppression increases the incidence of lymphoma and often this is of B cell origin.

The human liver microenvironment shapes the homing and function of CD4 T-cell populations.

Objective: Tissue-resident memory T cells (T) are vital immune sentinels that provide protective immunity. While hepatic CD8 T have been well described, little is known about the location, phenotype and function of CD4 T.

Design: We used multiparametric flow cytometry, histological assessment and novel human tissue coculture systems to interrogate the ex vivo phenotype, function and generation of the intrahepatic CD4 T-cell compartment.

An indolent cause of high-output heart failure in end-stage kidney disease-Application of the Nicoladoni-Israel-Branham test: A case report.

Background: A hemodynamically significant arteriovenous fistula (AVF) in end-stage kidney disease (ESKD) causes a high flow state, resulting in pathologic cardiovascular remodeling, and deserves timely clinical recognition.

Case: A 55-year-old woman with history of ESKD with deceased donor kidney transplant with failing graft function and baseline creatinine of 2.8 mg/dl presented to the clinic with nocturnal cough, orthopnea, dyspnea on exertion and pedal edema.

The Hyperlipidaemic Drug Fenofibrate Significantly Reduces Infection by SARS-CoV-2 in Cell Culture Models.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has caused a significant number of fatalities and worldwide disruption. To identify drugs to repurpose to treat SARS-CoV-2 infections, we established a screen to measure the dimerization of angiotensin-converting enzyme 2 (ACE2), the primary receptor for the virus. This screen identified fenofibric acid, the active metabolite of fenofibrate.

Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication.

The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with molecular dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5' UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure.

COVID-19 school closures and educational achievement gaps in Canada: Lessons from Ontario summer learning research.

The 2020 COVID-19 pandemic closed most Canadian public schools for six consecutive months between March and September. This paper explores possible impacts of that closure on student achievement. Longstanding research suggests that lengthy periods of time out of school generally create losses of literacy and numeracy skills and widen student achievement gaps.

Formulation of a Composite Nasal Spray Enabling Enhanced Surface Coverage and Prophylaxis of SARS-COV-2.

Airborne pathogens pose high risks in terms of both contraction and transmission within the respiratory pathways, particularly the nasal region. However, there is little in the way of adequate intervention that can protect an individual or prevent further spread. This study reports on a nasal formulation with the capacity to combat such challenges, focusing on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Hypothalamic-pituitary-adrenal axis regulation and organization in urban and rural song sparrows.

Urban habitats present animals with persistent disturbances and acute stressors not present in rural habitats or present at significantly lower levels. Differences in the glucocorticoid stress response could underlie colonization of these novel habitats. Despite urban habitats characterization as more stressful, previous comparisons of urban and rural birds have failed to find consistent differences in baseline and stress induced glucocorticoid levels.

Targeting Enclysis in Liver Autoimmunity, Transplantation, Viral Infection and Cancer.

Persistent liver inflammation can lead to cirrhosis, which associates with significant morbidity and mortality worldwide. There are no curative treatments beyond transplantation, followed by long-term immunosuppression. The global burden of end stage liver disease has been increasing and there is a shortage of donor organs, therefore new therapies are desperately needed.

Supramolecular Cylinders Target Bulge Structures in the 5' UTR of the RNA Genome of SARS-CoV-2 and Inhibit Viral Replication*.

The untranslated regions (UTRs) of viral genomes contain a variety of conserved yet dynamic structures crucial for viral replication, providing drug targets for the development of broad spectrum anti-virals. We combine in vitro RNA analysis with molecular dynamics simulations to build the first 3D models of the structure and dynamics of key regions of the 5' UTR of the SARS-CoV-2 genome. Furthermore, we determine the binding of metallo-supramolecular helicates (cylinders) to this RNA structure.

Cell-in-Cell Structures in the Liver: A Tale of Four E's.

The liver is our largest internal organ and it plays major roles in drug detoxification and immunity, where the ingestion of extracellular material through phagocytosis is a critical pathway. Phagocytosis is the deliberate endocytosis of large particles, microbes, dead cells or cell debris and can lead to cell-in-cell structures. Various types of cell endocytosis have been recently described for hepatic epithelia (hepatocytes), which are non-professional phagocytes.

Hepatocytes Delete Regulatory T Cells by Enclysis, a CD4 T Cell Engulfment Process.

CD4 T cells play critical roles in directing immunity, both as T helper and as regulatory T (Treg) cells. Here, we demonstrate that hepatocytes can modulate T cell populations through engulfment of live CD4 lymphocytes. We term this phenomenon enclysis to reflect the specific enclosure of CD4 T cells in hepatocytes.

Genetic inheritance and environment determine endocrine plasticity to urban living.

As urban areas continue to expand globally, understanding how and why species respond to novel habitats becomes increasingly important. Knowledge of the mechanisms behind observed phenotypic changes in urban animals will enable us to better evaluate the impact of urbanization on current and future generations of wildlife. Physiological changes, such as those involved in the endocrine stress response, may allow individuals to inhabit and thrive in urbanized areas, but it is currently unknown how these changes arise in natural populations.

Percutaneous screw fixation for painful non-union of lateral malleolus ankle fractures.

Introduction: Lateral malleolus non-union can cause pain and loss of function. Standard treatment involves open approach with debridement, bone-grafting and plate stabilisation, with published surgical site infection rates to 17%. To minimise the risk of soft tissue complications and allow early mobilisation, we describe a technique for percutaneous cannulated screw stabilisation.

The Reactive Oxygen Species-Mitophagy Signaling Pathway Regulates Liver Endothelial Cell Survival During Ischemia/Reperfusion Injury.

Ischemia/reperfusion injury (IRI) is the main cause of complications following liver transplantation. Reactive oxygen species (ROS) were thought to be the main regulators of IRI. However, recent studies demonstrate that ROS activate the cytoprotective mechanism of autophagy promoting cell survival.

Light at night disrupts nocturnal rest and elevates glucocorticoids at cool color temperatures.

Nighttime light pollution is quickly becoming a pervasive, global concern. Since the invention and proliferation of light-emitting diodes (LED), it has become common for consumers to select from a range of color temperatures of light with varying spectra. Yet, the biological impacts of these different spectra on organisms remain unclear.