No abstract

Many genes associated with familial Parkinson's disease contribute to mitochondrial morphology and function. Some of these genes, for example, Pink1 and Parkin, are part of a common pathway. The presenilin-associated rhomboid-like (PARL) gene was recently linked to familial Parkinson's disease. The PARL gene product is found in the inner mitochondrial membrane and cleaves the optic atrophy 1 protein, involved in mitochondrial morphology and apoptosis. In Drosophila, the PARL-related rhomboid-7 gene acts upstream of pink1 and parkin. However, such a genetic relationship is still unknown in vertebrates. Here, we show that the zebrafish genome comprises two parl paralogs: parla and parlb. Morpholino-mediated loss of parla and/or parlb function resulted in mild neurodegeneration, as evidenced by a lower density of dopaminergic neurons. Patterning of dopaminergic neurons was also perturbed in the ventral diencephalon. Morphants exhibited extensive cell death throughout the entire body as well as increased larval mortality. The morphant phenotype could be rescued by injection of human PARL mRNA, but not catalytically inactive PARL, suggesting functional conservation between the human and zebrafish proteins. More importantly, the zebrafish pink1 mRNA as well as the human PINK1 mRNA, but not kinase-dead nor Parkinson's disease-linked mutant PINK1 mRNA, also rescued the morphant phenotype, providing evidence that Parl genes may function upstream of Pink1, as part of a conserved pathway in vertebrates.

Background: Patients with terminal conditions are often admitted to the emergency department (ED) for acute medical services, but studies have suggested that multiple ED admissions may negatively impact end-of-life (EOL) care. Research have shown that incorporating palliative care (PC) is integral to optimal EOL care, but it is an aspect of medical practice that is often neglected. The current study sought to provide an overview of health outcomes and hospital costs of patients with cancer admitted to The Ottawa Hospital and/or received acute medical services during their final 2 weeks of life. Cost comparisons and estimates were made between hospital and hospice expenditures. Methods: We conducted a retrospective chart review of palliative patients who died at The Ottawa Hospital in 2012. A total of 130 patients who visited the ED within 2 weeks of death were included in the analyses. Results: In this cohort of patients, 71% of admitted patients did not have advanced care directives and 85% experienced a metastasis, but only 18% had a PC medical doctor. Patients were hospitalized, on average, for 7 days and hospitalization costs exceeded the estimated hospice cost by approximately 2.5 times (Can$1 041 170.00 at Can$8009.00/patient vs Can$401 570.00 at Can$3089.00/patient, respectively). Conclusion: Our study highlighted the importance of PC integration in high-risk patients, such as those in oncology. Patients in our sample had minimal PC involvement, low advanced care directives, and accrued high costs. Based on our analyses, we concluded that these patients would have likely benefited more from hospice care rather than hospitalization.