RESUMO
Spinal muscular atrophy (SMA) is a hereditary childhood disease that causes paralysis and progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN) protein, due to mutations in the Survival of Motor Neuron 1 gene. Nowadays there are no effective therapies available to treat patients with SMA, so our aim was to test whether the non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC), which exhibits neurotrophic properties, might have a therapeutic role or benefit in SMA. In this manuscript, we have demonstrated that TTC enhance the SMN expression in motor neurons "in vitro" and evaluated the effect of intramuscular injection of TTC-encoding plasmid in the spinal cord and the skeletal muscle of SMNdelta7 mice. For this purpose, we studied the weight and the survival time, as well as, the survival and cell death pathways and muscular atrophy. Our results showed that TTC treatment reduced the expression of autophagy markers (Becn1, Atg5, Lc3, and p62) and pro-apoptotic genes such as Bax and Casp3 in spinal cord. In skeletal muscle, TTC was able to downregulate the expression of the main marker of autophagy, Lc3, to wild-type levels and the expression of the apoptosis effector protein, Casp3. Regarding the genes related to muscular atrophy (Ankrd1, Calm1, Col19a1, Fbox32, Mt2, Myod1, NogoA, Pax7, Rrad, and Sln), TTC suggest a compensatory effect for muscle damage response, diminished oxidative stress and modulated calcium homeostasis. These preliminary findings suggest the need for further experiments to depth study the effect of TTC in SMA disease.
RESUMO
BACKGROUND: "New-growth communities" with rapidly growing Hispanic populations often have little experience with addressing the needs of this population. "Community readiness for change" is the degree to which a community is prepared to take action on an issue. OBJECTIVES: This study assessed the stage of community readiness for change in the area of Hispanic health in Nashville, using the community readiness model (CRM) and a community-based participatory research (CBPR) approach, through a partnership between an academic research center and a nonprofit, grassroots, Hispanic organization. METHODS: Qualitative and quantitative data were collected by trained community interviewers and the academic researcher using a semistructured questionnaire based on the CRM. The sample of key informants included (1) a purposive sample of 18 organizations, and (2) a convenience sample of 50 Hispanic community members. RESULTS: The organizations were at a higher stage (stage 5, preparation) than the Hispanic community members were (stage 4, preplanning), particularly in the dimensions of Leadership, Resources, and Knowledge of Efforts. The community members were also aware of fewer local efforts focused on Hispanic health than the organizations (average of 4.5 vs. 7.6). CONCLUSIONS: Recommendations were made for stageappropriate, community-level interventions. The assessment results are being used by Nashville Latino Health Coalition (NLHC) to plan collaborative initiatives to address Hispanic health needs in Nashville. This study demonstrates the utility of the CRM as a model for assessing a community's stage of readiness to take action, and the feasibility of applying it using a CBPR approach in a "new-growth" Hispanic community.