The Association between Individual Income and Aggressive End-of-Life Treatment in Older Cancer Decedents in Taiwan

Objectives

To examine the association of individual income and end of life (EOL) care in older cancer decedents in Taiwan.

Design

Retrospective cohort study.

Setting

National Health Insurance Research Database (NHIRD) in Taiwan.

Participants

28,978 decedents >65 years were diagnosed with cancer and died during 2009-2011 in Taiwan. Of these decedents, 10941, 16535, and 1502 were categorized by individual income as having low, moderate, and high SES, respectively.

Main outcome measures

Indicators of aggressiveness of EOL care: chemotherapy use before EOL, more than one emergency department (ER) visit, more than one hospital admission, hospital length of stay >14 days, intensive care unit (ICU) admission, and dying in a hospital.

Results

Low individual income was associated with more aggressive EOL treatment (estimate -0.30 for moderate income, -0.27 for high income, both p<0.01). The major source of aggressiveness was the tendency for older decedents with low income to die in the acute care hospital. The indicators had an increasing trend from 2009 to 2011, except for hospital stay >14 days.

Conclusions

Low individual income is associated with more aggressive EOL treatment in older cancer decedents. Public health providers should make available appropriate education and hospice resources to these decedents and their families, to reduce the amount of aggressive terminal care such decedents receive.     

Evaluation of bioenergy recovery processes treating organic residues from ethanol fermentation process

This study evaluates a two-stage bioprocess for recovering bioenergy in the forms of hydrogen and methane while treating organic residues of ethanol fermentation from tapioca starch. A maximum hydrogen production rate of 0.77 mmol H₂/g VSS/h can be achieved at volumetric loading rate (VLR) of 56 kg COD/m³/day. Batch results indicate that controlling conditions at S₀/X₀ = 12 with X₀ = 4000 mg VSS/L and pH 5.5-6 are important for efficient hydrogen production from fermentation residues. Hydrogen-producing bacteria enriched in the hydrogen bioreactor are likely utilizing lactate and acetate for biohydrogen production from ethanol-fermentation residues. Organic residues remained in the effluent of hydrogen bioreactor can be effectively converted to methane with a rate of 0.37 mmol CH₄/g VSS/h at VLR of 8 kg COD/m³/day. Approximately 90% of COD in ethanol-fermentation residues can be removed and among that 2% and 85.1% of COD can be recovered in the forms of hydrogen and methane, respectively.     

An ecdysone and tetracycline dual regulatory expression system for studies on Rac1 small GTPase-mediated signaling

Regulated expression systems are invaluable for studying gene function, offer advantages of dosage-dependent and temporally defined gene expression, and limit possible clonal variation when toxic or pleiotropic genes are overexpressed. Previously, establishment of inducible expression systems, such as tetracycline- and ecdysone-inducible systems, required assessment of the inducible characteristics of individual clones by tedious luciferase assays. Taking advantage of a green fluorescent protein (GFP) reporter controlled by tetracycline- or ecdysone-responsive element and fluorescence-activated cell sorting, we propose a simple and efficient strategy to select highly inducible cell lines according to their fluorescence profiles after transiently transfecting the candidate cell pools with a surrogate GFP reporter. We have demonstrated that tetracycline- and ecdysone-inducible systems could be set up in Madin-Darby canine kidney and HEK-293 cells by employing this selection scheme. Importantly, this dual regulatory expression system is applied in studying the complex interplay between two Ras-related small GTPases, Cdc42 and Rac1, on detachment-induced apoptosis. Furthermore, establishment of two tightly regulated expression systems in one target cell line could be of great advantage for dissecting small GTPase Rac1-transduced signaling pathways by using global gene expression approaches such as proteomic assays. fluorescence-activated cell sorting; green fluorescent protein; Ras small GTPases; anoikis     

Regulation of the catalytic behaviour of L-form starch phosphorylase from sweet potato roots by proteolysis

Starch phosphorylase (SP) is an enzyme used for the reversible phosphorolysis of the α-glucan in plant cells. When compared to its isoform in an animal cell, glycogen phosphorylase, a peptide containing 78 amino acids (L78) is inserted in the centre of the low-affinity type starch phosphorylase (L-SP). We found that the amino acid sequence of L78 had several interesting features including the presence of a PEST region, which serves as a signal for rapid degradation. Indeed, most L-SP molecules isolated from mature sweet potato roots were nicked in the middle of a molecule, but still retained their tertiary or quaternary structures, as well as full catalytic activity. The nicking sites on the L78 were identified by amino acid sequencing of these peptides, which also enabled us to propose a proteolytic process for L-SP. Enzyme kinetic studies of L-SP in the direction of starch synthesis indicated that the K_m decreased during the proteolytic process when starch was used as the limiting substrate, but the K_m for the other substrate (Glc-1-P) increased. On the other hand, the maximum velocities (V_max) increased for both substrates. Mobility of the nicked L-SP was retarded on a native polyacrylamide gel containing soluble starch, indicating the increased affinity for starch. Results in this study suggested that L78 and its proteolytic modifications might play a regulatory role on the catalytic behaviour of L-SP in starch biosynthesis.     

Phosphorylation of Enabled by the Drosophila Abelson Tyrosine Kinase Regulates the In Vivo Function and Protein-Protein Interactions of Enabled

Drosophila Enabled (Ena) is a member of a family of cytoskeleton-associated proteins including mammalian vasodilator-stimulated phosphoprotein and murine Enabled that regulate actin cytoskeleton assembly. Mutations in Drosophila ena were discovered as dominant genetic suppressors of mutations in the Abelson tyrosine kinase (Abl), suggesting that Ena and Abl function in the same pathway or process. We have identified six tyrosine residues on Ena that are phosphorylated by Abl in vitro and in vivo. Mutation of these phosphorylation sites to phenylalanine partially impaired the ability of Ena to restore viability to ena mutant animals, indicating that phosphorylation is required for optimal Ena function. Phosphorylation of Ena by Abl inhibited the binding of Ena to SH3 domains in vitro, suggesting that one effect of Ena phosphorylation may be to modulate its association with other proteins.     

Complex patterns of dopamine‐related gene expression in the ventral tegmental area of male zebra finches relate to dyadic interactions with long‐term female partners

Dopaminergic projections from the ventral tegmental area (VTA) to multiple efferent targets are implicated in pair bonding, yet the role of the VTA in the maintenance of long‐term pair bonds is not well characterized. Complex interactions between numerous neuromodulators modify activity in the VTA, suggesting that individual differences in patterns of gene expression in this region may explain individual differences in long‐term social interactions in bonded pairs. To test this hypothesis we used RNA‐seq to measure expression of over 8000 annotated genes in male zebra finches in established male‐female pairs. Weighted gene co‐expression network analysis identified a gene module that contained numerous dopamine‐related genes with TH found to be the most connected gene of the module. Genes in this module related to male agonistic behaviors as well as bonding‐related behaviors produced by female partners. Unsupervised learning approaches identified two groups of males that differed with respect to expression of numerous genes. Enrichment analyses showed that many dopamine‐related genes and modulators differed between these groups, including dopamine receptors, synthetic and degradative enzymes, the avian dopamine transporter and several GABA‐ and glutamate‐related genes. Many of the bonding‐related behaviors closely associated with VTA gene expression in the two male groups were produced by the male's partner, rather than the male himself. Collectively, results highlight numerous candidate genes in the VTA that can be explored in future studies and raise the possibility that the molecular/genetic organization of the VTA may be strongly shaped by a social partner and/or the strength of the pair bond.     

The recognition of DNA cleavage sites by porcine spleen topoisomerase II.

The cutting sites specificity of topoisomerase II from porcine spleen were determined by a modified Sanger's DNA sequencing method. The topoisomerase II prefers to cut DNA at the 3' side of A and leave 5' protruding end with two staggering bases. Through the free energy analysis for DNA duplex, we also found that the topoisomerase II seemed cut DNA preferably at energetically unstable regions. So it is concluded that the specific DNA cutting by porcine spleen topoisomerase II has two structural recognition factors: one is to localize around the energetically unstable region and another is to act at the 3' side of A base.