p62 overexpression induces TDP-43 cytoplasmic mislocalisation, aggregation and cleavage and neuronal death.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) that exist on a spectrum of neurodegenerative disease. A hallmark of pathology is cytoplasmic TDP-43 aggregates within neurons, observed in 97% of ALS cases and ~ 50% of FTLD cases. This mislocalisation from the nucleus into the cytoplasm and TDP-43 cleavage are associated with pathology, however, the drivers of these changes are unknown. p62 is invariably also present within these aggregates. We show that p62 overexpression causes TDP-43 mislocalisation into cytoplasmic aggregates, and aberrant TDP-43 cleavage that was dependent on both the PB1 and ubiquitin-associated (UBA) domains of p62. We further show that p62 overexpression induces neuron death. We found that stressors (proteasome inhibition and arsenic) increased p62 expression and that this shifted the nuclear:cytoplasmic TDP-43 ratio. Overall, our study suggests that environmental factors that increase p62 may thereby contribute to TDP-43 pathology in ALS and FTLD.

Understanding the role of stimulation in reflexology: development and testing of a robotic device.

Reflexology is a common choice of women with breast cancer as supportive care during treatment. It involves stimulation of specific locations of the feet called reflexes using a specialised walking motion with the thumb of the reflexologist. Reflexology has shown potential for the successful management of cancer and treatment-related symptoms and improvement in physical functioning; however to date, the mechanism of action for these improvements is unknown. One confounder to the study of reflexology is the 'human factor'. To study the effects of the stimulation of the reflexes independent of the 'human factor', there is a need for an alternative method for the delivery of reflexology. The objective of this work was to design and create a robotic reflexology device that would deliver a breast cancer-specific reflexology protocol to the feet of patients. A prototype robotic reflexology device was developed and tested for feasibility, safety and acceptability with breast cancer survivors (n= 13), and preliminary efficacy in symptom management and enhanced functional status with a sample of women undergoing chemotherapy for breast cancer (n= 13). Safety, feasibility and acceptability were established, and significant improvements from pre- to post-device-delivered reflexology were seen in symptom severity among women on chemotherapy.

Support for rural families of hospitalized infants: the parents' perspective.

The provision of family-centered care in the hospital arena has become a national commitment. Recognizing and supporting the family's role means evaluating whether attitudes, policies, and practices address the immediate and the long-term needs of the total family rather than just the current needs of the child. Results of a study to determine parents' perceptions of supportive services available in the hospital immediately following the birth of their child with special health care needs are reported. In-depth interviews with mothers living in rural areas were conducted. Mothers emphasized the importance of access to their child; the need for timely, honest, straightforward information about their child's condition and progress; the intense emotional reaction to the intensive care environment; and the importance of an early link to community-based early intervention services. Overall, parents conveyed the importance of recognizing the family as an integral part of the child. Implications and recommendations for family-centered services are discussed.