Quantitative measurement of postural sway in mouse models of human neurodegenerative disease

Detection of motor dysfunction in genetic mouse models of neurodegenerative disease requires reproducible, standardized and sensitive behavioral assays. We have utilized a Center of Pressure (CoP) assay in mice to quantify postural sway produced by genetic mutations that affect motor control centers of the brain. As a positive control for postural instability, wild type mice were injected with harmaline, a tremorigenic agent, and the average areas of the 95% confidence ellipse, which measures 95% of the CoP trajectory values recorded in a single trial, were measured. Ellipse area significantly increased in mice treated with increasing doses of harmaline and returned to control values after recovery. We also examined postural sway in mice expressing mutations that mimic frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) (T-279, P301L or P301L-NOS2(−/−) mice) and that demonstrate motor symptoms. These mice were then compared to a mouse model of Alzheimer’s disease (APPSwDI) that demonstrates cognitive, but not motor deficits. T-279 and P301L-NOS2(−/−) mice demonstrated a significant increase in CoP ellipse area compared to appropriate wild type control mice or to mice expressing the P301L mutation alone. In contrast, postural instability was significantly reduced in APPSwDI mice that have cognitive deficits but do not have associated motor deficits. The CoP assay provides a simple, sensitive and quantitative tool to detect motor deficits resulting from postural abnormalities in mice and may be useful in understanding the underlying mechanisms of disease

Relationships between family physicians’ referral for palliative radiotherapy, knowledge of indications for radiotherapy, and prior training: a survey of rural and urban family physicians

<p>Abstract</p> <p>Background</p> <p>The primary objective of this research was to assess the relationship between FPs’ knowledge of palliative radiotherapy (RT) and referral for palliative RT.</p> <p>Methods</p> <p>1001 surveys were sent to FPs who work in urban, suburban, and rural practices. Respondents were tested on their knowledge of palliative radiotherapy effectiveness and asked to report their self-assessed knowledge.</p> <p>Results</p> <p>The response rate was 33%. FPs mean score testing their knowledge of palliative radiotherapy effectiveness was 68% (SD = 26%). The majority of FPs correctly identified that painful bone metastases (91%), airway obstruction (77%), painful local disease (85%), brain metastases (76%) and spinal cord compression (79%) can be effectively treated with RT, though few were aware that hemoptysis (42%) and hematuria (31%) can be effectively treated. There was a linear relationship between increasing involvement in palliative care and both self-assessed (p < 0.001) and tested (p = 0.02) knowledge. FPs had higher mean knowledge scores if they received post-MD training in palliative care (12% higher; p < 0.001) or radiotherapy (15% higher; p = 0.002). There was a strong relationship between FPs referral for palliative radiotherapy and both self-assessed knowledge (p < 0.001) and tested knowledge (p = 0.01).</p> <p>Conclusions</p> <p>Self-assessed and tested knowledge of palliative RT is positively associated with referral for palliative RT. Since palliative RT is underutilized, further research is needed to assess whether family physician educational interventions improve palliative RT referrals. The current study suggests that studies could target family physicians already in practice, with educational interventions focusing on hemostatic and other less commonly known indications for palliative RT.</p