BMP4/Smad1 Signalling Promotes Spinal Dorsal Column Axon Regeneration and Functional Recovery After Injury.

Signalling through the BMP4/Smad1 pathway promotes corticospinal tract axon regeneration and functional recovery in mice. However, unlike humans and rats, mice do not cavitate. Here, we investigated if activation of the BMP4/Smad1 pathway promotes axon regeneration and functional recovery in a rat model that cavitates. We show that dorsal root ganglion neurons (DRGN) in injury models, including the non-regenerating dorsal column (DC) and the regenerating sciatic nerve (SN) crush and preconditioning (p) SN + DC (pSN + DC) paradigms, regulate the BMP4/Smad1 signalling pathway. For example, mRNA expression of positive regulators of the BMP4/Smad1 pathway was highly up-regulated whilst negative regulators were significantly down-regulated in DRGN in the regenerating SN and pSN + DC models compared to non-regenerating DC models, matched by concomitant changes in protein expression detected in DRGN by immunohistochemistry. BMP4 peptide promoted significant DRGN survival and disinhibited neurite outgrowth in vitro, whilst AAV-BMP4 delivery in vivo stimulated DC axon regeneration and functional recovery in a model that cavitates. Our results show that activation of the BMP4/Smad1 pathway is a potential therapeutic target in the search for axon regenerative signalling pathways in the CNS.

Implementing novel models of posttreatment care for cancer survivors: Enablers, challenges and recommendations.

AIM: The American Society of Clinical Oncology and US Institute of Medicine emphasize the need to trial novel models of posttreatment care, and disseminate findings. In 2011, the Victorian State Government (Australia) established the Victorian Cancer Survivorship Program (VCSP), funding six 2-year demonstration projects, targeting end of initial cancer treatment. Projects considered various models, enrolling people of differing cancer types, age and residential areas. We sought to determine common enablers of success, as well as challenges/barriers. METHODS: Throughout the duration of the projects, a formal "community of practice" met regularly to share experiences. Projects provided regular formal progress reports. An analysis framework was developed to synthesize key themes and identify critical enablers and challenges. Two external reviewers examined final project reports. Discussion with project teams clarified content. RESULTS: Survivors reported interventions to be acceptable, appropriate and effective. Strong clinical leadership was identified as a critical success factor. Workforce education was recognized as important. Partnerships with consumers, primary care and community organizations; risk stratified pathways with rapid re-access to specialist care; and early preparation for survivorship, self-management and shared care models supported positive project outcomes. Tailoring care to individual needs and predicted risks was supported. Challenges included: lack of valid assessment and prediction tools; limited evidence to support novel care models; workforce redesign; and effective engagement with community-based care and issues around survivorship terminology. CONCLUSION: The VCSP project outcomes have added to growing evidence around posttreatment care. Future projects should consider the identified enablers and challenges when designing and implementing survivorship care.