MUC1 is a transmembrane glycoprotein expressed by normal breast epithelium and virtually all breast cancers. MUC1 is normally restricted to the apical surface of epithelia and loss of this polarized distribution in breast carcinomas is associated with lymph node metastasis. Our previous work found that MUC1 can bind intercellular adhesion molecule-1 (ICAM-1), mediating adhesion of breast cancer cells to a simulated blood vessel wall, and also triggering a calcium-based signal in the MUC1-bearing cells. It is possible that the depolarized membrane distribution of MUC1 in breast carcinomas may facilitate interactions with stromal/endothelial ICAM-1 leading to adhesion and subsequent migration through the vessel wall. In the current study, we provide evidence that ICAM-1 can influence the migration of cells that express endogenous or transfected MUC1. Migration across a gelatin-coated Transwell membrane could be increased in a step-wise manner by the sequential addition of ICAM-1-expressing cells (endothelial cells and fibroblasts), and ICAM-1-inducing inflammatory cytokines (tumour necrosis factor-alpha and interleukin-1 beta). Antibodies against MUC1 or ICAM-1, but not a control antibody, could abrogate migratory increases. Cells that did not express MUC1 were unresponsive to ICAM-1. Our current findings build on our earlier work, by suggesting that the end result of the MUC1/ICAM-1-mediated cell-cell adhesion and calcium-based signal is migration. This has implications for the exit of circulating tumour cells from the vasculature, as well as tumour cell migration through fibroblast-containing stroma underlying the endothelial wall.

Benzodiazepines are recognised as being potentially inappropriate medications for seniors due to their considerable side-effect profile, yet they are commonly prescribed and infrequently discontinued (deprescribed). The study’s primary objective was the deprescription or the dose reduction of benzodiazepines among newly hospitalised seniors using a patient education intervention. A 3-month duration quality improvement study based on the plan–do–study–act model was conducted across two units (3C and 4D) in the Glenrose Rehabilitation Hospital to improve benzodiazepine deprescribing among newly admitted seniors (65 years or older) who were using benzodiazepines. The primary outcome measure was the number of eligible patients who had benzodiazepine deprescribing initiated. A patient education intervention comprising a structured medication review, written patient education (the Eliminating Medications Through Patient Ownership of End Results (EMPOWER) brochure) and at least one brief supportive counselling session by the clinical pharmacist or physician was applied to all eligible patients. All 12 eligible patients consented to benzodiazepine deprescribing; however, only 11 of them (92%) initiated benzodiazepine deprescribing. Six of the 11 patients (55%) had their benzodiazepines discontinued, with the 5 remaining patients (45%) achieving greater than 50% dosage reduction. Seven patients (64%) experienced side effects during the deprescribing process, with over half (57%, n=4) of these seven patients experiencing worsening anxiety symptoms. Five of the 11 patients (45%) required benzodiazepine substitute medications. The use of a structured patient education intervention involving the use of a structured medication review, written patient education material and one-on-one patient counselling can promote benzodiazepine deprescribing. Although worsening anxiety was frequently observed, this was easily managed by the substitution of a more appropriate and clinically indicated medication, which was well tolerated and acceptable by all of our participants. Targeted screening for the presence of anxiety would help to guide the deprescribing process and the need for medication substitution.

Although our understanding of the apoptotic processes is gradually increasing, many important aspects remain obscure. These include interconnections between pathways, wavelength-specific differences and cell type differences.

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Background: Legionnaires disease is the systemic manifestation of an infection by the gram-negative bacterium Legionella pneumophila. It most commonly presents with pneumonia, but can also cause extrapulmonary manifestations like cardiac, renal, gastrointestinal as well as neurologic symptoms like encephalopathy. It tends to occur in people who are elderly, immunocompromised and those with impaired respiratory (smokers) or cardiac (advanced heart failure) functions. The Legionella Urinary antigen is commonly used to diagnose Legionella infection. Almost half of the patients diagnosed with Legionnaires disease exhibit neurologic signs and symptoms. These neurologic abnormalities are usually not evident on neuroimaging, laboratory findings, and neuropathology.