ABSTRACT
The PRediction of short-term Outcomes in preGNant wOmen with Suspected preeclampsIa Study (PROGNOSIS) Asia validated the use of the soluble fms-like tyrosine 1/placental growth factor (sFlt-1/PlGF) ratio cutoff value of ≤38 to rule out the occurrence of preeclampsia in the short term in Asian women. We assessed the economic impact of the introduction of the sFlt-1/PlGF ratio test for predicting preeclampsia in Japan using data from the Japanese cohort of PROGNOSIS Asia. The cost analysis was developed with estimates in either a no-test scenario, with clinical decisions based on standard diagnostic procedures alone, or a test scenario, in which the sFlt-1/PlGF ratio test was used in addition to standard diagnostic procedures. For both scenarios, rates of hospitalization and other test characteristics were obtained from the results for the Japanese cohort in PROGNOSIS Asia. The total cost per patient was the main outcome of this cost analysis model. Introduction of the sFlt-1/PlGF ratio test using a cutoff value of 38 resulted in a reduced hospitalization rate compared with the rate in the no-test scenario (14.4% versus 8.7%). The reduction in the rate of hospitalizations led to an estimated 16 373 JPY reduction in healthcare costs per patient. The sFlt-1/PlGF ratio test is likely to reduce the unnecessary hospitalization of women at low risk of developing preeclampsia in the short term while also identifying high-risk individuals requiring appropriate management. Reducing unnecessary hospitalizations would result in significant cost savings in the Japanese healthcare system.
Subject(s)
Pre-Eclampsia , Prenatal Diagnosis , Biomarkers/blood , Cohort Studies , Cost-Benefit Analysis , Female , Humans , Japan , Placenta Growth Factor/blood , Pre-Eclampsia/blood , Pre-Eclampsia/diagnosis , Pregnancy , Prenatal Diagnosis/economics , Vascular Endothelial Growth Factor Receptor-1/bloodABSTRACT
Mitochondrial morphology is dynamically controlled by a balance between fusion and fission. The physiological importance of mitochondrial fission in vertebrates is less clearly defined than that of mitochondrial fusion. Here we show that mice lacking the mitochondrial fission GTPase Drp1 have developmental abnormalities, particularly in the forebrain, and die after embryonic day 12.5. Neural cell-specific (NS) Drp1(-/-) mice die shortly after birth as a result of brain hypoplasia with apoptosis. Primary culture of NS-Drp1(-/-) mouse forebrain showed a decreased number of neurites and defective synapse formation, thought to be due to aggregated mitochondria that failed to distribute properly within the cell processes. These defects were reflected by abnormal forebrain development and highlight the importance of Drp1-dependent mitochondrial fission within highly polarized cells such as neurons. Moreover, Drp1(-/-) murine embryonic fibroblasts and embryonic stem cells revealed that Drp1 is required for a normal rate of cytochrome c release and caspase activation during apoptosis, although mitochondrial outer membrane permeabilization, as examined by the release of Smac/Diablo and Tim8a, may occur independently of Drp1 activity.
Subject(s)
Embryonic Development/physiology , GTP Phosphohydrolases/metabolism , Mitochondrial Proteins/metabolism , Synapses/enzymology , Animals , Animals, Newborn , Blotting, Western , Brain/cytology , Brain/embryology , Brain/metabolism , Cell Line , Cells, Cultured , Cytochromes c/metabolism , Embryo, Mammalian/cytology , Embryo, Mammalian/embryology , Embryo, Mammalian/metabolism , Embryonic Development/genetics , Female , Fibroblasts/cytology , Fibroblasts/metabolism , Fibroblasts/ultrastructure , GTP Phosphohydrolases/genetics , Immunohistochemistry , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Electron , Microscopy, Fluorescence , Mitochondria/enzymology , Mitochondria/ultrastructure , Mitochondrial Proteins/genetics , Neurons/cytology , Neurons/metabolism , Synapses/metabolism , Synapses/ultrastructure , Time FactorsABSTRACT
Organelles are inherited to daughter cells beyond dynamic changes of the membrane structure during mitosis. Mitochondria are dynamic entities, frequently dividing and fusing with each other, during which dynamin-related GTPase Drp1 is required for the fission reaction. In this study, we analyzed mitochondrial dynamics in mitotic mammalian cells. Although mitochondria in interphase HeLa cells are long tubular network structures, they are fragmented in early mitotic phase, and the filamentous network structures are subsequently reformed in the daughter cells. In marked contrast, tubular mitochondrial structures are maintained during mitosis in Drp1 knockdown cells, indicating that the mitochondrial fragmentation in mitosis requires mitochondrial fission by Drp1. Drp1 was specifically phosphorylated in mitosis by Cdk1/cyclin B on Ser-585. Exogenous expression of unphosphorylated mutant Drp1S585A led to reduced mitotic mitochondrial fragmentation. These results suggest that phosphorylation of Drp1 on Ser-585 promotes mitochondrial fission in mitotic cells.