Genetic and Environmental Factors in Parkinson's Disease Converge on Immune Function and Inflammation.

Idiopathic Parkinson's disease (iPD) is a movement disorder characterized by the degeneration of dopaminergic neurons and aggregation of the protein α-synuclein. Patients with iPD vary in age of symptom onset, rate of progression, severity of motor and non-motor symptoms, and extent of central and peripheral inflammation. Genetic and environmental factors are believed to act synergistically in iPD pathogenesis.

The second generation mixed lineage kinase-3 (MLK3) inhibitor CLFB-1134 protects against neurotoxin-induced nigral dopaminergic neuron loss.

Dopaminergic neurons express mixed lineage kinases which regulate the expression of cell death genes. In Parkinson's disease, cell death via apoptosis is prevalent, and previous work testing mixed lineage kinase inhibitors in animal models suggested the inhibitors had some neuroprotective potential. CLFB-1134 is a new, brain-penetrant inhibitor specific for MLK3, tested here in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of dopaminergic depletion and nigral neuron death in mice.

Evolving management strategies in esophageal perforation: surgeons using nonoperative techniques to improve outcomes.

Background: Management of acute esophageal perforation continues to evolve. We hypothesized that treatment of these patients at a tertiary referral center is more important than beginning treatment within 24 hours, and that the evolving application of nonsurgical treatment techniques by surgeons would produce improved outcomes.

Study Design: Demographics and outcomes of patients treated for esophageal perforation from 1989 to 2009 were recorded in an Institutional Review Board-approved database.