IKK promotes naïve T cell survival by repressing RIPK1-dependent apoptosis and activating NF-κB.

The inhibitor of κB kinase (IKK) complex regulates the activation of the nuclear factor κB (NF-κB) family of transcription factors. In addition, IKK represses extrinsic cell death pathways dependent on receptor-interacting serine/threonine-protein kinase 1 (RIPK1) by directly phosphorylating this kinase. Here, we showed that peripheral naïve T cells in mice required the continued expression of IKK1 and IKK2 for their survival; however, the loss of these cells was only partially prevented when extrinsic cell death pathways were blocked by either deleting (which encodes the apoptosis-inducing caspase 8) or inhibiting the kinase activity of RIPK1.

IFN-γ and PPARδ influence the efficacy and retention of multipotent adult progenitor cells in graft vs host disease.

Cell-based therapy for the treatment of inflammatory disorders has focused on the application of mesenchymal stromal cells (MSCs) and multipotent adult progenitor cells (MAPCs). Despite the recent positive findings in industry-sponsored clinical trials of MSCs and MAPCs for graft vs host disease (GvHD), cell therapy is efficacious in some but not all patients, highlighting the need to identify strategies to enhance cell-based therapeutic efficacy. Here, we demonstrate the capacity for interferon (IFN)-γ licensing to enhance human MAPC efficacy and retention following early administration in a humanized mouse model of acute GvHD (aGvHD).

Evaluation of optimised 3D turbo spin echo and gradient echo MR pulse sequences of the knee at 3T and 1.5T.

Introduction: To investigate the impact of parameter optimisation for novel three-dimensional 3D sequences at 1.5T and 3T on resultant image quality.

Methods: Following institutional review board approval and acquisition of informed consent, MR phantom and knee joint imaging on healthy volunteers (n = 16) was performed with 1.

Multipotent Adult Progenitor Cells Suppress T Cell Activation in Models of Homeostatic Proliferation in a Prostaglandin E2-Dependent Manner.

Lymphodepletion strategies are used in the setting of transplantation (including bone marrow, hematopoietic cell, and solid organ) to create space or to prevent allograft rejection and graft versus host disease. Following lymphodepletion, there is an excess of IL-7 available, and T cells that escape depletion respond to this cytokine undergoing accelerated proliferation. Moreover, this environment promotes the skew of T cells to a Th1 pro-inflammatory phenotype.

The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?

Mesenchymal stromal cells (MSC) have emerged as promising cell therapies for multiple conditions based on demonstrations of their potent immunomodulatory and regenerative capacities in models of inflammatory disease. Understanding the effects of MSC on T cells has dominated the majority of work carried out in this field to date; recently, however, a number of studies have shown that the therapeutic effect of MSC requires the presence of macrophages. It is timely to review the mechanisms and manner by which MSC modulate macrophage populations in order to design more effective MSC therapies and clinical studies.

Hepatocyte Growth Factor Is Required for Mesenchymal Stromal Cell Protection Against Bleomycin-Induced Pulmonary Fibrosis.

Unlabelled: : The incidence of idiopathic pulmonary fibrosis is on the rise and existing treatments have failed to halt or reverse disease progression. Mesenchymal stromal cells (MSCs) have potent cytoprotective effects, can promote tissue repair, and have demonstrated efficacy in a range of fibrotic lung diseases; however, the exact mechanisms of action remain to be elucidated. Chemical antagonists and short hairpin RNA knockdown were used to identify the mechanisms of action used by MSCs in promoting wound healing, proliferation, and inhibiting apoptosis.

Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection.

Members of the Burkholderia cepacia complex (Bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (CF), resulting in a gradual lung function decline and, ultimately, patient death. The Bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of Bcc bacteria to lung epithelial cells.

Imaging of bone metastasis: An update.

Early detection of skeletal metastasis is critical for accurate staging and optimal treatment. This paper briefly reviews our current understanding of the biological mechanisms through which tumours metastasise to bone and describes the available imaging methods to diagnose bone metastasis and monitor response to treatment. Among the various imaging modalities currently available for imaging skeletal metastasis, hybrid techniques which fuse morphological and functional data are the most sensitive and specific, and positron emission tomography (PET)/computed tomography and PET/magnetic resonance imaging will almost certainly continue to evolve and become increasingly important in this regard.

Suppression of IL-7-dependent Effector T-cell Expansion by Multipotent Adult Progenitor Cells and PGE2.

T-cell depletion therapy is used to prevent acute allograft rejection, treat autoimmunity and create space for bone marrow or hematopoietic cell transplantation. The evolved response to T-cell loss is a transient increase in IL-7 that drives compensatory homeostatic proliferation (HP) of mature T cells. Paradoxically, the exaggerated form of this process that occurs following lymphodepletion expands effector T-cells, often causing loss of immunological tolerance that results in rapid graft rejection, autoimmunity, and exacerbated graft-versus-host disease (GVHD).

Jagged-1 is required for the expansion of CD4+ CD25+ FoxP3+ regulatory T cells and tolerogenic dendritic cells by murine mesenchymal stromal cells.

Introduction: Mesenchymal stromal cells (MSC) have well defined immunomodulatory properties including the suppression of lymphocyte proliferation and inhibition of dendritic cell (DC) maturation involving both cell contact and soluble factors. These properties have made MSC attractive candidates for cellular therapy. However, the mechanism underlying these characteristics remains unclear.

Imaging of periprosthetic infection.

Periprosthetic infection is one of the most challenging and difficult complications in orthopaedics. It can result in significant patient distress and disability, with repeated surgeries, increased cost and utilization of medical resources, and in rare cases even mortality. The biggest challenge to date is the correct diagnosis of periprosthetic infection and implementation of effective treatment regimens capable of eradicating the organism.

Imaging of the postoperative hip.

A basic understanding of the surgical approach, technique, and potential complications in addition to the types of hardware used is essential in interpreting postoperative imaging of the hip. This article reviews the various surgical approaches to the hip and hardware components in total hip arthroplasty and hip preservation surgery and the potential complications that may arise. The various surgical treatments in the management of acetabular dysplasia and avascular necrosis and the imaging appearances of these on different imaging modalities are also discussed.

Intramedullary versus extramedullary alignment of the tibial component in the Triathlon knee.

Background: Long term survivorship in total knee arthroplasty is significantly dependant on prosthesis alignment. Our aim was determine which alignment guide was more accurate in positioning of the tibial component in total knee arthroplasty. We also aimed to assess whether there was any difference in short term patient outcome.

Three-dimensional magnetic resonance imaging analysis of hip morphology in the assessment of femoral acetabular impingement.

Aim: To determine a possible association between femoral-acetabular impingement (FAI) volume and the development of labral tear using a three-dimensional (3D) model reconstruction of the acetabulum and the femoral head.

Materials And Methods: Magnetic resonance arthrography images of the hip in 42 patients with pain and suspected labral tear were acquired using a 1.5T MRI machine.

Whole-body imaging modalities in oncology.

This article outlines the expanding approaches to whole-body imaging in oncology focusing on whole-body MRI and comparing it to emerging applications of whole-body CT, scintigraphy, and above all PET CT imaging. Whole-body MRI is widely available, non-ionizing and rapidly acquired, and inexpensive relative to PET CT. While it has many advantages, WBMRI is non-specific and, when compared to PET CT, is less sensitive.

The role of whole-body imaging in the diagnosis, staging, and follow-up of multiple myeloma.

Multiple myeloma is one of the most common hematological malignancies and accounts for significant morbidity and mortality. In the past, detection of myelomatous deposits by radiography was the main method of radiological assessment in this disease. However, in recent years the introduction of whole-body imaging techniques, specifically low-dose whole-body computed tomography, whole-body magnetic resonance imaging, and positron emission tomography, has facilitated a more comprehensive assessment of this heterogeneous and often diffuse disease.

Comminuted fracture of the thoracic spine.

Background: Road deaths fell initially after the introduction of the penalty points but despite this, the rate of spinal injuries remained unchanged.

Aims: We report a patient with a dramatic spinal injury, though without neurological deficit. We discuss the classification, management and economic impact of these injuries.

Pseudoaneurysm of the occipital artery: an unusual cause of persisting headache after minor head injury.

Post-traumatic pseudoaneurysms of the extracranial arteries in the scalp are uncommon sequelae of head injury. We report on a patient who presented four weeks after a minor head injury with a tender, pulsating and enlarging mass in the course of the left occipital artery. There was associated headache radiating to the vertex.