Staphylococcal Esx Proteins Modulate Apoptosis and Release of Intracellular Staphylococcus aureus during Infection in Epithelial Cells

The opportunistic pathogen Staphylococcus aureus is one of the major causes of health care-associated infections. S. aureus is primarily an extracellular pathogen, but it was recently reported to invade and replicate in several host cell types. The ability of S. aureus to persist within cells has been implicated in resistance to antimicrobials and recurrent infections. However, few staphylococcal proteins that mediate intracellular survival have been identified. Here we examine if EsxA and EsxB, substrates of the ESAT-6-like secretion system (Ess), are important during intracellular S. aureus infection. The Esx proteins are required for staphylococcal virulence, but their functions during infection are unclear. While isogenic S. aureus esxA and esxB mutants were not defective for epithelial cell invasion in vitro, a significant increase in early/late apoptosis was observed in esxA mutant-infected cells compared to wild-type-infected cells. Impeding secretion of EsxA by deleting C-terminal residues of the protein also resulted in a significant increase of epithelial cell apoptosis. Furthermore, cells transfected with esxA showed an increased protection from apoptotic cell death. A double mutant lacking both EsxA and EsxB also induced increased apoptosis but, remarkably, was unable to escape from cells as efficiently as the single mutants or the wild type. Thus, using in vitro models of intracellular staphylococcal infection, we demonstrate that EsxA interferes with host cell apoptotic pathways and, together with EsxB, mediates the release of S. aureus from the host cell.     

Transient Leukaemia: Leukaemia or Leukaemoid? A Diagnostic Dilemma

We report a case of a newborn male who had mongoloid slant and was hypotonic at birth. Routine investigations revealed leucocytosis (WBC > 70,000/cmm) with 50% blasts in peripheral blood film. Marrow examination confirmed the excess of blasts. Karyotyping revealed 47, XY + 21 chromosomes. Due to absence of clinical symptoms, the baby was kept on follow-up without treatment. Within 7 weeks, PBF and bone marrow findings returned to normal, and the child was diagnosed as having Transient leukaemia with Down syndrome.     

Canakinumab: Promises and Future in Cardiometabolic Diseases and Malignancy

Inflammation has proven in multiple studies to be responsible for the progression of cardiometabolic diseases and malignancies. The interleukin family has been critically associated with progression of atherosclerosis, insulin resistance, and various malignancies. Given the advent of pharmacologic interleukin-1 (IL-1) inhibition, this pathway can potentially be targeted to improve outcomes. In the recently concluded Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial, investigators looked at the potential role of IL-1 (especially IL-1β) inhibition in halting the progression of atherosclerosis. In the subset analysis of the data from this trial, IL-1β inhibition with canakinumab was found to have beneficial effects in other cardiometabolic diseases characterized by inflammation, like diabetes, stroke, and chronic kidney disease, and also in patients with lung cancer. In this article, we will try to review the current literature on the role of canakinumab in the treatment of cardiometabolic diseases and malignancies.     

Effect of soft tissue thickness over the posterior border of the vertebral body and disc space on cage placement during posterior lumbar interbody fusion: A cadaveric study

In the present study, we investigated whether there is a difference between visual depth (VD) and radiological image depth (RD) of cages (i.e., structural interbody support devices) placed in disc spaces during posterior lumbar interbody fusion and whether soft tissues covering the posterior border of the vertebral body and associated disc space are the cause of any observed differences. Using digital calipers, cages were inserted at a depth of 5 mm from the soft tissues covering the posterior border of the vertebral body and disc space under direct vision; this depth was defined as VD. After insertion, RD was measured in triplicate. The reliability of RD measurements was evaluated using an intraclass coefficient test. To identify the cause of differences between VD and RD, the thicknesses of soft tissues were measured microscopically. A total of 40 lumbar intervertebral disc spaces with cages were evaluated. The mean RD of cages was 3.12 mm, while the mean difference between the VD and RD of cages (DVRD) was 1.91 mm. On histological examination, the mean thickness of the soft tissue was 2.02 mm. Comparative analysis between histological values and DVRD showed no statistical difference (P = 1.14, 1.55, 0.06). There was a significant difference between VD and RD during cage placement, and soft tissue structure appeared to be responsible for the DVRD of inserted cages. Therefore, cages should be inserted deeper to account for differences between visual and radiological image depths. Clin. Anat. 25:1066–1073, 2012. © 2012 Wiley Periodicals, Inc.     

Initial experience with a self-expanding retrievable stent for recanalization of large vessel occlusions in acute ischemic stroke

Introduction  

Quicker recanalization results in better clinical outcomes in patients with acute ischemic strokes. We describe our experience with the use of a self-expanding, fully retrievable stent in acute intracranial occlusions.