Evaluation of the Efficacy of an Online Learning Module to Increase Wound Care Theoretical Knowledge Amongst Medical Students.

Objective: We developed and evaluated an online learning module for teaching wound care basics to junior medical learners, which was assessed for its ability to increase theoretical knowledge of wound care, and medical learners' perceptions on the use of an online module to teach wound care practices.

Design: Between February 2022 to November 2022, participants were enrolled into our unblinded, matched-pair single-arm study. Participants completed a pre- and postquiz prior to and after completing the online module, respectively.

Qualitative research in vascular surgery.

Qualitative research aims to understand and describe subjective experiences and perceptions. Qualitative and mixed-methods research, in which quantitative and qualitative research methods are combined, is playing an increasingly bigger role in vascular surgery research. The aim of this review was to describe the fundamentals of qualitative research methods and its application in vascular surgery.

Exploring the psychosocial needs of persons with lower extremity amputation and feasibility of internet cognitive behavioural therapy: a qualitative study.

Purpose: Following major lower extremity amputation (LEA), patients experience significant emotional distress and are at risk for anxiety and depression. There is a lack of mental health supports for this population, and internet-based cognitive behavioural therapy (iCBT) may be a useful resource to meet this need. The purpose of this study was to use a qualitative approach to explore the mental health needs of LEA patients and to gauge their attitudes of the use of iCBT to help them cope with their amputation.

Integration of Th17- and Lymphotoxin-Derived Signals Initiates Meningeal-Resident Stromal Cell Remodeling to Propagate Neuroinflammation.

Tertiary lymphoid tissues (TLTs) have been observed in the meninges of multiple sclerosis (MS) patients, but the stromal cells and molecular signals that support TLTs remain unclear. Here, we show that T helper 17 (Th17) cells induced robust TLTs within the brain meninges that were associated with local demyelination during experimental autoimmune encephalitis (EAE). Th17-cell-induced TLTs were underpinned by a network of stromal cells producing extracellular matrix proteins and chemokines, enabling leukocytes to reside within, rather than simply transit through, the meninges.

A TNF-α-CCL20-CCR6 axis regulates Nod1-induced B cell responses.

Innate immune responses provoke the accumulation of leukocytes at sites of inflammation. In addition to monocytes and granulocytes, B cells also participate in antimicrobial innate immune responses; however, the mechanisms for accumulation of B cells to sites of inflammation are not well understood. To study B cell accumulation following systemic inflammation, we used a model synthetic ligand that stimulates a specific pattern recognition molecule, nucleotide-binding oligomerization domain-containing protein 1 (Nod1).

A sphingosine-1-phosphate receptor 1-directed agonist reduces central nervous system inflammation in a plasmacytoid dendritic cell-dependent manner.

Gradients of the sphingolipid sphingosine-1-phosphate (S1P) are responsible for the egress of lymphocytes from lymph nodes by activating the S1P1 receptor expressed on the surface of lymphocytes. Small molecule drugs that downregulate S1P receptors induce the sequestration of lymphocytes within lymph nodes, thus preventing lymphocytes from accessing sites of inflammation. In particular, FTY720, a pan-S1P receptor agonist, has been efficacious in the treatment of multiple sclerosis as well as its animal model, experimental autoimmune encephalomyelitis (EAE), by virtue of its ability to restrain lymphocytes within the lymph nodes, thus precluding their migration into the CNS.

Fine-tuning of dendritic cell biology by the TNF superfamily.

Members of the tumour necrosis factor (TNF) superfamily have been implicated in a wide range of biological functions, and their expression by cells of the immune system makes them appealing targets for immunomodulation. One common theme for TNF superfamily members is their coordinated expression at the interface between antigen-specific T cells and antigen-presenting dendritic cells and, by virtue of this expression pattern, TNF superfamily members can shape T cell immune responses. Understanding how to manipulate such functions of the TNF superfamily may allow us to tip the balance between immunity and tolerance in the context of human disease.

Nuclear factor-κB1 controls the functional maturation of dendritic cells and prevents the activation of autoreactive T cells.

Mature dendritic cells (DCs) are crucial for the induction of adaptive immune responses and perturbed DC homeostasis can result in autoimmune disease. Either uncontrolled expansion or enhanced survival of DCs can result in a variety of autoimmune diseases in mouse models. In addition, increased maturation signals, through overexpression of surface Toll-like receptors (TLRs) or stimulation by type I interferon (IFN), has been associated with systemic autoimmunity.

LTβR and CD40: working together in dendritic cells to optimize immune responses.

Generating an immune response tailored to destroy an infecting organism while limiting bystander damage involves guiding T-cell activation using a variety of cues taken from the immunogen (antigen type, dose, and persistence, accompanying danger signals) as well as the host (tissue environment, T-cell frequency, and affinity for antigen). Dendritic cells (DCs) serve as translators of much of this information and are critically required for effective pathogen and tumor clearance. Moreover, dysregulation of DC activation can lead to autoimmunity.

LTβR signaling in dendritic cells induces a type I IFN response that is required for optimal clonal expansion of CD8+ T cells.

During an immune response, antigen-bearing dendritic cells (DCs) migrate to the local draining lymph node and present antigen to CD4(+) helper T cells. Antigen-activated CD4(+) T cells then up-regulate TNF superfamily members including CD40 ligand and lymphotoxin (LT)αβ. Although it is well-accepted that CD40 stimulation on DCs is required for DC licensing and cross-priming of CD8(+) T-cell responses, it is likely that other signals are integrated into a comprehensive DC activation program.

Retinoic acid modulates chromatin to potentiate tumor necrosis factor alpha signaling on the DIF2 promoter.

Transcriptional activation by nuclear hormone receptors is well characterized, but their cooperation with other signaling pathways to activate transcription remains poorly understood. Tumor necrosis factor alpha (TNFalpha) and all-trans retinoic acid (RA) induce monocytic differentiation of acute promyelocytic leukemia (APL) cells in a synergistic manner. We used the promoter of DIF2, a gene involved in monocytic differentiation, to model the mechanism underlying the cooperative induction of target genes by RA and TNFalpha.

Expression of lymphotoxin-alphabeta on antigen-specific T cells is required for DC function.

During an immune response, activated antigen (Ag)-specific T cells condition dendritic cells (DCs) to enhance DC function and survival within the inflamed draining lymph node (LN). It has been difficult to ascertain the role of the tumor necrosis factor (TNF) superfamily member lymphotoxin-alphabeta (LTalphabeta) in this process because signaling through the LTbeta-receptor (LTbetaR) controls multiple aspects of lymphoid tissue organization. To resolve this, we have used an in vivo system where the expression of TNF family ligands is manipulated only on the Ag-specific T cells that interact with and condition Ag-bearing DCs.

The lymphotoxin pathway: beyond lymph node development.

The first studies of mice deficient in lymphotoxin-alpha (LTalpha), LTbeta and LTbetaR revealed the seminal discovery that the LTbetaR signaling is critical for the development of lymph nodes and Peyer's patches during embryogenesis. Since these initial findings, it is increasingly appreciated that signaling through the lymphotoxin-beta receptor (LTbetaR) plays a key role in numerous biological processes in the adult animal, including the maintenance of specialized stromal cell types and the homeostatic control of chemokine expression within the lymphoid tissues. A major focus of our laboratory is to understand the relevance of LTbetaR signaling in initiating immune responses both dependent and independent of its role in maintaining the organization of lymphoid tissues.

BAFF induces a hyper-IgA syndrome in the intestinal lamina propria concomitant with IgA deposition in the kidney independent of LIGHT.

BAFF is a peripheral B cell survival factor and can mediate antibody (Ab) class switching. Over-expression of BAFF in mice results in B cell hyperplasia, elevated serum immunoglobulin (Ig), spontaneous germinal centre (GC) reactions and mild glomerulonephritis (GN). Here we show that, in addition to driving excessive levels of serum IgA, BAFF over-expression results in increased IgA levels within the intestinal lamina propria (LP) and deposition of IgA immune complexes in the renal glomerular mesangium.