Does the Canadian Occupational Performance Measure (COPM) Capture the Complex Experiences of Cancer Survivors? A Mixed Methods Approach.

Occupational therapy practitioners are uniquely positioned to address the needs of cancer survivors. This study aimed to understand the complex needs of survivors using The Canadian Occupational Performance Measure and in-depth interviewing. A convergent, mixed methods approach was utilized with a purposive sample of 30 cancer survivors. The results indicate that while the COPM can be a practical tool to address basic occupational performance problems, the in-depth interviews exposed these challenges are intricately connected to identity, relationships, and roles. Implications for occupational therapy practitioners include a critical approach to evaluation and interventions to capture the complex needs of survivors.

Cancer Survivors' Disability Experiences and Identities: A Qualitative Exploration to Advance Cancer Equity.

Eliminating cancer-related disparities is a global public health priority. Approximately 40% of cancer survivors experience long-term effects of cancer which can lead to activity limitations and participation restrictions; yet discussions of disability are largely absent from clinical and research cancer health equity agendas. The purpose of this study was to explore how cancer survivors experience and make sense of the long-term disabling effects of cancer and its treatments. In this qualitative study, data were collected via in-depth semi-structured interviews with survivors of breast cancer, head and neck cancer, and sarcoma (n = 30). Data were analyzed thematically using a 2-phase iterative process proceeding from descriptive to conceptual coding. Survivors experienced a wide range of long-term physical, sensory, cognitive, and emotional effects, that intertwined to restrict their participation in self-care, work, leisure, and social roles. While the interaction between impairments and participation restrictions meets the definition of disability; participants articulated a range of responses when asked about their disability identity, including (1) rejecting, (2) othering, (3) acknowledging, and (4) affirming. Findings may be indicative of structural and internalized ableism which can impede cancer care and survivorship. To support cancer survivors' transition to post-treatment life, cancer care providers should implement anti-ableist practices and engage in frank discussions about cancer's long-term impacts.

Tissue-Specific stem cell differentiation in an in vitro airway model.

The respiratory tract is the primary site of exposure to airborne compounds, with the bronchial epithelium providing one of the first lines of defence. A growing need exists for an accurate in vitro model of the bronchial epithelium. Here, normal human bronchial epithelial (NHBE) cells cultured at an air/liquid interface create a fully differentiated, in-vivo-like model of the human bronchial epithelium. Developmental characterisation includes (i) trans-epithelial electrical resistance, (ii) morphology and (iii) bronchial cell specific stains/markers. It is concluded that the basal/progenitor cells create a pseudo-stratified, mucociliary NHBE model containing basal, serous, Clara, goblet and ciliated cells, reflective of the normal human bronchial epithelium (days 24-33 ALI culture).

Basal forebrain cholinergic lesions reduce heat shock protein 72 response but not pathology induced by the NMDA antagonist MK-801 in the rat cingulate cortex.

Non-competitive N-methyl-D-aspartate (NMDA) antagonists, in addition to their neuroprotective potential, possess neurotoxic properties and induce seizures and psychosis. MK-801 induces cytoplasmic vacuoles and heat shock protein in pyramidal neurones in the rodent posterior cingulate and retrosplenial cortex. The mechanism of this neurotoxicity is unclear, involving many neurotransmitter systems. The aim of this study was to investigate the role of cholinergic pathways from the nucleus basalis of Meynert in mediating MK-801-induced neurotoxicity. Cholinergic projections from the nucleus basalis of Meynert were lesioned by focal injection of 192-IgG-saporin (80 ng), which after 7 days reduced the number of cholinergic cell bodies by 70% in the lesioned nucleus compared to the uninjected nucleus. Following a unilateral cholinergic lesion, MK-801 (5 mg/kg s.c.) induced expression of hsp72 mRNA (6 h) and HSP72 protein immunoreactivity (24 h) was reduced by 42 and 60%, respectively in the ipsilateral compared to the contralateral posterior cingulate. Despite this apparent protective effect, the unilateral cholinergic lesion did not affect the degree of neuronal vacuolation (6 h), necrosis (24 h) or the large and prolonged increase in cerebral blood flow which occurred over the first 9h following MK-801 administration. These results demonstrate that cholinergic neurones in the nucleus basalis of Meynert play an important role in the heat shock response to NMDA antagonist-induced neurotoxicity but also reveal an unexpected divergence between the heat shock response and the pathophysiological response. This suggests that other cholinergic pathways or non-cholinergic mechanisms are responsible for the pathological changes induced by MK-801.

CTLA4-Ig abrogates the anti-globulin response and prolongs cardiac allograft survival after anti-CD2 treatment.

CD2 is expressed on T cells and NK cells and is important in T cell activation, making it a potential target for immune intervention. Here, we report a series of experiments aimed at defining the ability of mAbs directed against the CD2 molecule to prevent cardiac allograft rejection in low and high responder rat strain combinations. Administration of the mouse anti-rat CD2 mAbs OX34 or OX55 around the time of transplantation prolonged survival of fully allogeneic Lewis (RT1l) cardiac allografts in low responder DA (RT1a) recipients (MST 14 days for OX55 and >100 days for OX34). Treatment with OX34 prolonged graft survival in the reciprocal high responder DA to Lewis rat strain combination (MST 19 days) and when combined with CTLA4-Ig resulted in long-term graft survival (MST>100 days). Despite these in vivo effects, OX34 had little effect on in vitro assays of lymphocyte activation. Instead, the ability of OX34 to extend allograft survival correlated with T cell depletion. Administration of OX34 induced a similar degree of CD4 T cell depletion in DA and Lewis recipients, but the CD4 depletion observed was more transient in Lewis recipients. Lewis, but not DA strain rats, developed an anti-murine Ig response. Combined treatment with CTLA4-Ig abolished the anti-globulin response to OX34 in Lewis recipients, prolonged circulation of OX34 and increased the extent and duration of CD4 depletion. We conclude that anti-CD2 treatment effectively prolongs cardiac allograft survival and addition of CTLA4-Ig increases its efficacy by abrogating the production of neutralising antibodies.

Inhibition of proliferation and signalling mechanisms in human lymphocytes by fluvastatin.

1. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) reduce serum cholesterol and have proven benefits in the treatment of cardiovascular disease. However, recent work suggests that statins may exert immunosuppressive effects in isolated lymphocytes and in solid organ transplant recipients. Fluvastatin does not interfere with the metabolism of commonly used immunosuppressive agents and, therefore, may have benefits in transplant recipients. 2. The aim of the present study was to investigate the potential immunomodulatory effects of fluvastatin in vitro in human lymphocytes and the underlying effects on signal transduction. 3. In vitro, fluvastatin (10 micromol/L) caused a time-dependent inhibition of T cell proliferation in response to cross-linking of CD3. 4. Thymidine incorporation was reduced by 22, 81 and 92% at days 1, 3 and 5, respectively. 5. Mevalonate (1 micromol/L) treatment for 4 or 24 h significantly reduced the inhibitory effects of fluvastatin; the reversal was abrogated by simultaneous exposure to mevalonate and a farnesyl transferase inhibitor. 6. At a subcellular level, fluvastatin treatment was associated with reduced functional activity of Ras-dependent extracellular signal-regulated kinase pathways and of Rho-dependent p38 activation. 7. These data suggest that the potential immunosuppressive actions of statins involve inhibition of subcellular pathways dependent on isoprenylation of signal peptides, including Ras, Rho and related G-proteins.