Elevation of the TP53 isoform Δ133p53β in glioblastomas: an alternative to mutant p53 in promoting tumor development

As tumor protein 53 (p53) isoforms have tumor‐promoting, migration, and inflammatory properties, this study investigated whether p53 isoforms contributed to glioblastoma progression. The expression levels of full‐length TP53α (TAp53α) and six TP53 isoforms were quantitated by RT‐qPCR in 89 glioblastomas and correlated with TP53 mutation status, tumor‐associated macrophage content, and various immune cell markers. Elevated levels of Δ133p53β mRNA characterised glioblastomas with increased CD163‐positive macrophages and wild‐type TP53. In situ‐based analyses found Δ133p53β expression localised to malignant cells in areas with increased hypoxia, and in cells with the monocyte chemoattractant protein C‐C motif chemokine ligand 2 (CCL2) expressed. Tumors with increased Δ133p53β had increased numbers of cells positive for macrophage colony‐stimulating factor 1 receptor (CSF1R) and programmed death ligand 1 (PDL1). In addition, cells expressing a murine ‘mimic’ of Δ133p53 (Δ122p53) were resistant to temozolomide treatment and oxidative stress. Our findings suggest that elevated Δ133p53β is an alternative pathway to TP53 mutation in glioblastoma that aids tumor progression by promoting an immunosuppressive and chemoresistant environment. Adding Δ133p53β to a TP53 signature along with TP53 mutation status will better predict treatment resistance in glioblastoma. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Ward-Specific Rates of Nasal Cocolonization with Methicillin-Susceptible and -Resistant Staphylococcus spp. and Potential Impact on Molecular Methicillin-Resistant Staphylococcus aureus Screening Tests

We report that the rates of nasal cocolonization with methicillin-susceptible Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococci can vary widely between patients admitted to different wards within a single hospital. Such cocolonization can greatly influence the performance of molecular methicillin-resistant S. aureus (MRSA) screening tests depending on the methods used and targets selected.     

Dynamic spatio-temporal imaging of early reflow in a neonatal rat stroke model

The aim of the study was to better understand blood-flow changes in large arteries and microvessels during the first 15 minutes of reflow in a P7 rat model of arterial occlusion. Blood-flow changes were monitored by using ultrasound imaging with sequential Doppler recordings in internal carotid arteries (ICAs) and basilar trunk. Relative cerebral blood flow (rCBF) changes were obtained by using laser speckle Doppler monitoring. Tissue perfusion was measured with [¹⁴C]-iodoantipyrine autoradiography. Cerebral energy metabolism was evaluated by mitochondrial oxygen consumption. Gradual increase in mean blood-flow velocities illustrated a gradual perfusion during early reflow in both ICAs. On ischemia, the middle cerebral artery (MCA) territory presented a residual perfusion, whereas the caudal territory remained normally perfused. On reflow, speckle images showed a caudorostral propagation of reperfusion through anastomotic connections, and a reduced perfusion in the MCA territory. Autoradiography highlighted the caudorostral gradient, and persistent perfusion in ventral and medial regions. These blood-flow changes were accompanied by mitochondrial respiration impairment in the ipsilateral cortex. Collectively, these data indicate the presence of a primary collateral pathway through the circle of Willis, providing an immediate diversion of blood flow toward ischemic regions, and secondary efficient cortical anastomoses in the immature rat brain.     

Trabecular Metal Cones Combined With Short Cemented Stem Allow Favorable Outcomes in Aseptic Revision Total Knee Arthroplasty

BackgroundThe purpose of this study was to compare the functional outcomes and implant survivorship at a minimum of 5 years of follow-up of several reconstruction techniques with or without metaphyseal cone and stems of variable length.MethodsA retrospective comparative matched analysis was performed from 2 prospectively collected databases. Only patients who underwent revision total knee arthroplasty procedures for aseptic causes using a single design of rotating hinge knee with a minimum of 5 years of follow-up were analyzed. Patients were separated into 3 groups: trabecular metal (TM) cones + short cemented stems (TM + short stem [SS]), TM cones + long uncemented stems (TM + long stem [LS]), and no cone (NC) + long uncemented stems (NC + LS). A matching process based on age (±5 years) was realized.ResultsAbout 99 patients were included; 33 in the TM + SS group, 33 in the TM + LS group, and 33 in the NC + LS group. The mean time of follow-up was 9.3 years. A significant difference of the improvement of subscale pain, symptom, activities of daily living, quality of life of the Knee Injury and Osteoarthritis Outcome score and knee, function of the Knee Society Score was observed in favor of TM + SS group compared with the 2 other groups. At 8 years of survivorship, the components free of revision for any cause were 90.9% for the TM + SS group, 84.9% for the TM + LS group, and 90.6% for the NC + LS group.ConclusionThe use of a short cemented tibial stem combined with a TM cone in revision total knee arthroplasty offers identical survival rate with better functional outcome compared with the use of a long uncemented stem associated with TM cones or metallic augments at a minimum of 5 years of follow-up.     

Hepatitis E in Transplantation

Hepatitis E virus (HEV) has a worldwide distribution and is known to cause acute and fulminant hepatitis. However, over the last few years, it has been shown to also cause chronic hepatitis and cirrhosis in immunosuppressed patients, especially solid-organ-transplant patients. In immunocompetent and immunosuppressed patients, HEV is also associated with extra-hepatic manifestations, such as neurological symptoms and kidney injury. Unfortunately, a diagnostic assay for HEV infection is still not available in all countries. Reduction of immunosuppression is the first-line therapeutic option for organ-transplant patients with chronic hepatitis. In addition, ribavirin is highly efficient at treating chronic HEV infection. In this comprehensive review, we summarize the current knowledge regarding HEV diagnosis, its natural history, clinical manifestations, and treatments in patients with a solid-organ transplant.     

Synthesis and in vitro evaluation of MR molecular imaging probes using J591 mAb‐conjugated SPIONs for specific detection of prostate cancer

Carcinoma of the prostate is the most frequent diagnosed malignant tumor in men and is the second leading cause of cancer‐related death in this group. The cure rate of prostate cancer is highly dependent on the stage of disease at the diagnosis and early detection is key to designing effective treatment strategies. The objective of the present study is to make a specific MR imaging probe for targeted imaging of cancer cells. We take advantage of the fact that many types of prostate cancer cells express high levels of prostate‐specific membrane antigen (PSMA) on their cell surface. The imaging strategy is to use superparamagnetic iron oxide nanoparticles (SPIONs), attached to an antibody (J591) that binds to the extracellular domain of PSMA, to specifically enhance the contrast of PSMA‐expressing prostate cancer cells. Conjugation of mAb J591 to commercial SPIONs was achieved using a heterobifunctional linker, sulfo‐SMCC. Two types of prostate cancer cell lines were chosen for experiments: LNCaP (PSMA+) and DU145 (PSMA?). MRI and cell uptake experiments demonstrated the high potential of the synthesized nanoprobe as a specific MRI contrast agent for detection of PSMA‐expressing prostate cancer cells. Copyright © 2012 John Wiley & Sons, Ltd.