Promoting regeneration while blocking cell death preserves motor neuron function in a model of ALS.

Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease of motor neurons with very few treatment options. We had previously found that motor neuron degeneration in a mouse model of ALS can be delayed by deleting the axon damage sensor MAP3K12 or dual leucine zipper kinase (DLK). However, DLK is also involved in axon regeneration, prompting us to ask whether combining DLK deletion with a way to promote axon regeneration would result in greater motor neuron protection. To achieve this, we used a mouse line that constitutively expresses ATF3, a master regulator of regeneration in neurons. Although there is precedence for each individual strategy in the SOD1G93A mouse model of ALS, these have not previously been combined. By several lines of evidence including motor neuron electrophysiology, histology and behaviour, we observed a powerful synergy when combining DLK deletion with ATF3 expression. The combinatorial strategy resulted in significant protection of motor neurons with fewer undergoing cell death, reduced axon degeneration and preservation of motor function and connectivity to muscle. This study provides a demonstration of the power of combinatorial therapy to treat neurodegenerative disease.

Obstructive sleep apnea and arrhythmia: A systemic review.

There is a growing consensus in the scientific community that suggests a strong association between obstructive sleep apnea (OSA) and cardiovascular (CVD) conditions and events, including coronary artery disease, hypertension, arrhythmia, heart failure, and sudden cardiac death. We reviewed evidence on the relationship between OSA and arrhythmia. Our conclusion, based on our review of the literature, is that the evidence supports a strong link between OSA and cardiovascular mortality, which warrants treating OSA. Continuous positive airway pressure (CPAP) appears to reduce the CVD consequences of OSA. Future research is expected to clarify the benefits and optimal application of these treatment approaches.

Impact of diabetes on heart failure incidence in adults with ischemic heart disease.

BACKGROUND: Ischemic heart disease (IHD) is the most potent risk factor for heart failure (HF). Our study aims to evaluate the incremental impact of diabetes on the incidence of HF in individuals with IHD. METHODS: Data from the NHANES Epidemiologic Follow-Up Study (Baseline: 1971 to 1974) were linked to the facility and mortality files up to 1992. Our analyses were restricted to patients with IHD without prevalent HF at baseline. The cumulative incidence of HF in patients with diabetes and IHD versus those with IHD alone was assessed using failure curves. Cox proportional hazards models were used to control for important covariates. All analyses incorporated the complex sample design by including the weights and clustering variables. RESULTS: Out of the 14,407 participants, 497 had IHD without prevalent HF and had information about diabetes status. Among these participants, the cumulative incidence of HF was 38.1% for those with diabetes (n=63) and 26.5% in those without diabetes (n=434) (log-rank p-value<0.005). The multivariate hazard ratio (adjusted for age, BMI, alcohol consumption, hypertension, high cholesterol, and smoking) for incident HF for people who had myocardial infarction (MI) and diabetes compared to people who had MI alone was 2.98 (95% CI 1.51, 5.88). CONCLUSION: Among participants with MI, those with diabetes had a substantially higher incidence of HF than those without diabetes. Based on these findings, practitioners should focus greater attention on patients with diabetes and previous MI in order to potentially prevent incident HF.