A Canadian Retrospective Chart Review Evaluating Concomitant Methotrexate De-escalation Patterns in Patients with Rheumatoid Arthritis Treated with Biologic or Targeted Synthetic DMARDs.

Introduction: Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX)-anchored therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); however, tolerability issues often lead to non-adherence. Canadian data on MTX tapering and/or withdrawal following b/tsDMARD initiation are minimal. This chart review assessed frequency of MTX tapering or withdrawal following b/tsDMARD initiation and the impact on disease status in Canadian adults with RA.

Real-World Effectiveness of Upadacitinib for Treatment of Rheumatoid Arthritis in Canadian Patients: Interim Results from the Prospective Observational CLOSE-UP Study.

Introduction: Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase 4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA.

Methods: Adults with RA who initiated treatment with once daily UPA (15 mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included.

Septin 7: actin cross-organization is required for axonal association of Schwann cells.

Myelin sheaths present two distinct domains: compacted myelin spirals and flanking non-compacted cytoplasmic channels, where lipid and protein segregation is established by unknown mechanisms. Septins, a conserved family of membrane and cytoskeletal interacting GTPases, form intracellular diffusion barriers during cell division and neurite extension and are expressed in myelinating cells. Septins, particularly septin 7 (Sept7), the central constituent of septin polymers, are associated with the cytoplasmic channels of myelinating cells.

Lipidome and proteome map of myelin membranes.

To understand the molecular anatomy of myelin membranes, we performed a large-scale, liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS)-based lipidome and proteome screen on freshly purified human and murine myelin fractions. We identified more than 700 lipid moieties and above 1,000 proteins in the two species, including 284 common lipids and 257 common proteins. This study establishes the first comprehensive map of myelin membrane components in human and mice.

Atomic force microscopy reveals important differences in axonal resistance to injury.

Axonal degeneration after traumatic brain injury and nerve compression is considered a common underlying cause of temporary as well as permanent disability. Because a proper functioning of neural network requires phase coherence of all components, even subtle changes in circuitry may lead to network failure. However, it is still not possible to determine which axons will recover or degenerate after injury.

Substrate Micropatterning as a New in Vitro Cell Culture System to Study Myelination.

Myelination is a highly regulated developmental process whereby oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system ensheathe axons with a multilayered concentric membrane. Axonal myelination increases the velocity of nerve impulse propagation. In this work, we present a novel in vitro system for coculturing primary dorsal root ganglia neurons along with myelinating cells on a highly restrictive and micropatterned substrate.

Rapid assembly of functional presynaptic boutons triggered by adhesive contacts.

CNS synapse assembly typically follows after stable contacts between "appropriate" axonal and dendritic membranes are made. We show that presynaptic boutons selectively form de novo following neuronal fiber adhesion to beads coated with poly-d-lysine (PDL), an artificial cationic polypeptide. As demonstrated by atomic force and live confocal microscopy, functional presynaptic boutons self-assemble as rapidly as 1 h after bead contact, and are found to contain a variety of proteins characteristic of presynaptic endings.

Cellular localization of kinin B1 receptor in the spinal cord of streptozotocin-diabetic rats with a fluorescent [Nalpha-Bodipy]-des-Arg9-bradykinin.

Background: The kinin B1 receptor (B1R) is upregulated by pro-inflammatory cytokines, bacterial endotoxins and hyperglycaemia-induced oxidative stress. In animal models of diabetes, it contributes to pain polyneuropathy. This study aims at defining the cellular localization of B1R in thoracic spinal cord of type 1 diabetic rats by confocal microscopy with the use of a fluorescent agonist, [Nalpha-Bodipy]-des-Arg9-BK (BdABK) and selective antibodies.

Tau interacts with Golgi membranes and mediates their association with microtubules.

Tau, a microtubule-associated protein enriched in the axon, is known to stabilize and promote the formation of microtubules during axonal outgrowth. Several studies have reported that tau was associated with membranes. In the present study, we further characterized the interaction of tau with membranous elements by examining its distribution in subfractions enriched in either Golgi or endoplasmic reticulum membranes isolated from rat brain.

Fragmentation of the Golgi apparatus induced by the overexpression of wild-type and mutant human tau forms in neurons.

Tau is a microtubule-associated protein enriched in the axonal compartment. In several neurodegenerative diseases including Alzheimer's disease, hyperphosphorylated tau accumulates in the somatodendritic compartment, self-aggregates, and forms neurofibrillary tangles. A fragmentation of the neuronal Golgi apparatus (GA) was also observed in Alzheimer's disease.

Interaction of microtubule-associated protein-2 and p63: a new link between microtubules and rough endoplasmic reticulum membranes in neurons.

Neurons are polarized cells presenting two distinct compartments, dendrites and an axon. Dendrites can be distinguished from the axon by the presence of rough endoplasmic reticulum (RER). The mechanism by which the structure and distribution of the RER is maintained in these cells is poorly understood.