Effect of remote ischemic preConditioning on liver injury in patients undergoing liver resection: the ERIC-LIVER trial

OBJECTIVE: Novel hepatoprotective strategies are needed to improve clinical outcomes during liver surgery. There is mixed data on the role of remote ischemic preconditioning (RIPC). We investigated RIPC in partial hepatectomy for primary hepatocellular carcinoma (HCC). METHODS: This was a Phase II, single-center, sham-controlled, randomized controlled trial (RCT). The primary hypothesis was that RIPC would reduce acute liver injury following surgery indicated by serum alanine transferase (ALT) 24 h following hepatectomy in patients with primary HCC, compared to sham. Patients were randomized to receive either four cycles of 5 min/5 min arm cuff inflation/deflation immediately prior to surgery, or sham. Secondary endpoints included clinical, biochemical and pathological outcomes. Liver function measured by Indocyanine Green pulse densitometry was performed in a subset of patients. RESULTS: 24 and 26 patients were randomized to RIPC and control groups respectively. The groups were balanced for baseline characteristics, except the duration of operation was longer in the RIPC group. Median ALT at 24 h was similar between groups (196 IU/L IQR 113.5-419.5 versus 172.5 IU/L IQR 115-298 respectively, p = 0.61). Groups were similar in secondary endpoints. CONCLUSION: This RCT did not demonstrate beneficial effects with RIPC on serum ALT levels 24 h after partial hepatectomy

Brief Report: Testing the Psychometric Properties of the Spence Children’s Anxiety Scale (SCAS) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) in Autism Spectrum Disorder

Anxiety is a prevalent and impairing co-morbidity among individuals with autism spectrum disorder (ASD), yet assessment measures, including screening tools, are seldom validated with autism samples. We explored the psychometric properties of the child and parent reports of the Spence Children’s Anxiety Scale (SCAS) and the Screen for Anxiety Related Disorder-71 (SCARED-71) with 49 males with ASD (10–16 years, 63% co-occurring anxiety). Both measures had excellent internal consistency and fair-good parent–child agreement. The SCAS has a higher proportion of items evaluating observable behaviors. Predictive power of the measures did not differ. Higher cut-points in the parent reports (SCARED only) and lower cut-points in the child reports may enhance prediction in this sample. Choice of measure and cut-points should be considered alongside intended purpose

Seroepidemiology of coxsackievirus A6, coxsackievirus A16, and Enterovirus 71 infections among children and adolescents in Singapore, 2008-2010

10.1371/journal.pone.0127999PLoS ONE105e012799

Sponsor ownership in Asian REITs

This study examines the relationship between sponsor ownership and firm performance proxied by firm value, operating cash flow, and dividend policy with Asian real estate investment trusts (REITs) in Japan, Hong Kong, Malaysia, and Singapore for the period from 2002 to 2012, focusing on both the incentive alignment effect and the entrenchment effect. Our study sheds new light on effective corporate governance for Asian REITs that are prone to agency problems. Such agency problems arise from the inequitable distribution of power to sponsors that results from the external management structure. The findings suggest that larger sponsor ownership aligns the interests of sponsors and minority shareholders and enhances the performance of Asian REITs, while such an effect diminishes as sponsors become more entrenched. We find that the incentive alignment effect and entrenchment effect are primarily driven by developer-sponsored REITs. Also evident is that the presence of institutional investors mitigates agency problems and increases firm performance

Detection of Oxidation Products of 5-Methyl-2′-Deoxycytidine in Arabidopsis DNA

Epigenetic regulations play important roles in plant development and adaptation to environmental stress. Recent studies from mammalian systems have demonstrated the involvement of ten-eleven translocation (Tet) family of dioxygenases in the generation of a series of oxidized derivatives of 5-methylcytosine (5-mC) in mammalian DNA. In addition, these oxidized 5-mC nucleobases have important roles in epigenetic remodeling and aberrant levels of 5-hydroxymethyl-29-deoxycytidine (5-HmdC) were found to be associated with different types of human cancers. However, there is a lack of evidence supporting the presence of these modified bases in plant DNA. Here we reported the use of a reversed-phase HPLC coupled with tandem mass spectrometry method and stable isotope-labeled standards for assessing the levels of the oxidized 5-mC nucleosides along with two other oxidatively induced DNA modifications in genomic DNA of Arabidopsis. These included 5- HmdC, 5-formyl-29-deoxycytidine (5-FodC), 5-carboxyl-29-deoxycytidine (5-CadC), 5-hydroxymethyl-29-deoxyuridine (5- HmdU), and the (59S) diastereomer of 8,59-cyclo-29-deoxyguanosine (S-cdG). We found that, in Arabidopsis DNA, the levels of 5-HmdC, 5-FodC, and 5-CadC are approximately 0.8 modifications per 106 nucleosides, with the frequency of 5-HmdC (per 5-mdC) being comparable to that of 5-HmdU (per thymidine). The relatively low levels of the 5-mdC oxidation products suggest that they arise likely from reactive oxygen species present in cells, which is in line with the lack of homologous Tetfamily dioxygenase enzymes in Arabidopsis

The Side Population in Human Lung Cancer Cell Line NCI-H460 Is Enriched in Stem-Like Cancer Cells

Lung cancer is among the most lethal malignancies with a high metastasis and recurrence rate. Recent studies indicate that tumors contain a subset of stem-like cancer cells that possess certain stem cell properties. Herein, we used Hoechst 33342 dye efflux assay and flow cytometry to isolate and characterize the side population (SP) cells from human lung cancer cell line NCI-H460 (H460). We show that the H460 SP cells harbor stem-like cells as they can readily form anchorage-independent floating spheres, possess great proliferative potential, and exhibit enhanced tumorigenicity. Importantly, the H460 SP cells were able to self-renew both in vitro and in vivo. Finally, we show that the H460 SP cells preferentially express ABCG2 as well as SMO, a critical mediator of the Hedgehog (HH) signaling, which seems to play an important role in H460 lung cancer cells as its blockage using Cyclopamine greatly inhibits cell-cycle progression. Collectively, our results lend further support to the existence of lung cancer stem cells and also implicate HH signaling in regulating large-cell lung cancer (stem) cells

An internal ribosome entry site in the 5′ untranslated region of epidermal growth factor receptor allows hypoxic expression

The expression of epidermal growth factor receptor (EGFR/ERBB1/HER1) is implicated in the progress of numerous cancers, a feature that has been exploited in the development of EGFR antibodies and EGFR tyrosine kinase inhibitors as anti-cancer drugs. However, EGFR also has important normal cellular functions, leading to serious side effects when EGFR is inhibited. One damaging characteristic of many oncogenes is the ability to be expressed in the hypoxic conditions associated with the tumour interior. It has previously been demonstrated that expression of EGFR is maintained in hypoxic conditions via an unknown mechanism of translational control, despite global translation rates generally being attenuated under hypoxic conditions. In this report, we demonstrate that the human EGFR 5′ untranslated region (UTR) sequence can initiate the expression of a downstream open reading frame via an internal ribosome entry site (IRES). We show that this effect is not due to either cryptic promoter activity or splicing events. We have investigated the requirement of the EGFR IRES for eukaryotic initiation factor 4A (eIF4A), which is an RNA helicase responsible for processing RNA secondary structure as part of translation initiation. Treatment with hippuristanol (a potent inhibitor of eIF4A) caused a decrease in EGFR 5′ UTR-driven reporter activity and also a reduction in EGFR protein level. Importantly, we show that expression of a reporter gene under the control of the EGFR IRES is maintained under hypoxic conditions despite a fall in global translation rates

A Downstream CpG Island Controls Transcript Initiation and Elongation and the Methylation State of the Imprinted Airn Macro ncRNA Promoter

A CpG island (CGI) lies at the 5′ end of the Airn macro non-protein-coding (nc) RNA that represses the flanking Igf2r promoter in cis on paternally inherited chromosomes. In addition to being modified on maternally inherited chromosomes by a DNA methylation imprint, the Airn CGI shows two unusual organization features: its position immediately downstream of the Airn promoter and transcription start site and a series of tandem direct repeats (TDRs) occupying its second half. The physical separation of the Airn promoter from the CGI provides a model to investigate if the CGI plays distinct transcriptional and epigenetic roles. We used homologous recombination to generate embryonic stem cells carrying deletions at the endogenous locus of the entire CGI or just the TDRs. The deleted Airn alleles were analyzed by using an ES cell imprinting model that recapitulates the onset of Igf2r imprinted expression in embryonic development or by using knock-out mice. The results show that the CGI is required for efficient Airn initiation and to maintain the unmethylated state of the Airn promoter, which are both necessary for Igf2r repression on the paternal chromosome. The TDRs occupying the second half of the CGI play a minor role in Airn transcriptional elongation or processivity, but are essential for methylation on the maternal Airn promoter that is necessary for Igf2r to be expressed from this chromosome. Together the data indicate the existence of a class of regulatory CGIs in the mammalian genome that act downstream of the promoter and transcription start