Overexpression of MicroRNA-122 Resists Oxidative Stress-Induced Human Umbilical Vascular Endothelial Cell Injury by Inhibition of p53.

Deep venous thrombosis (DVT) constitutes a great threat to health worldwide. Endothelial cell injury and dysfunction comprise the critical contributor for the development of DVT. However, the mechanism behind it remains poorly elucidated. The study is aimed at investigating the role of microRNA-122 (miR-122) and oxidative stress on DVT. The results showed that miR-122 overexpression dampened H2O2-evoked cytotoxic injury in human umbilical vein endothelial cells (HUVECs) by increasing cell viability, suppressing cell apoptosis and oxidative stress injury. Notably, miR-122 overexpression attenuated provasoconstriction factor endothelin-1 (ET-1) expression in HUVECs exposed to H2O2 but enhanced the productions of vasodilatation factor Prostaglandin F1α (PGF1α). Moreover, inhibition of miR-122 had the opposite results. miR-122 could inhibit the expression of p53. Low expression of p53 could enhance the protection of miR-122 on HUVEC injury. This study highlights that miR-122 overexpression may restore H2O2-induced HUVEC injury by regulating the expression of p53.

Basic Processes in Dynamic Decision Making: How Experimental Findings About Risk, Uncertainty, and Emotion Can Contribute to Police Decision Making.

In this paper, we review basic findings from experimental studies in judgment and decision making that could contribute to designing policies and trainings to enhance police decision making. Traditional judgment and decision-making research has focused on simple choices between hypothetical gambles, which has been criticized for its lack of generalizability to real world contexts. Over the past 15 years, researchers have focused on understanding the dynamic processes in decision making. This recent focus has allowed for the possibility of more generalizable applications of basic decision science to social issues. We review recent work in three dynamic decision-making topics: dynamic accumulation of evidence in the decision to shoot or not shoot, how previous decisions influence current choices, and how the cognitive and neurological processing of fear influences decisions and decision errors. We conclude this review with a summary of how basic experimental research can apply in policing and training.

Utility of Alternative Effect Size Statistics and the Development of a Web-Based Calculator: Shiny-AESC.

Alternative displays of effect size statistics can enhance the understandability and impact of validity evidence in a variety of applied settings. Arguably, the proliferation of alternative effect size statistics has been limited due to the lack of user-friendly tools to create them. Common statistical packages do not readily produce these alternative effect sizes and existing tools are outdated and inaccessible. In this paper, I introduce a free-to-use web-based calculator (https://dczhang.shinyapps.io/expectancyApp/) for generating alternative effect size displays from empirical data. This calculator requires no mathematical or programming expertise, and therefore, is ideal for academics and practitioners. I also present results from an empirical study that demonstrates the benefits of alternative effect size displays for enhancing lay people's perceived understandability of validity information and attitudes toward the use of standardized testing for college admissions.

Evaluation of thyroid test utilization through analysis of population-level data.

BACKGROUND: Inappropriate laboratory test utilization can result in unnecessary patient testing and increased healthcare costs. While several thyroid function tests are available, thyroid-stimulating hormone (TSH) is recommended as the first-line test for investigating and monitoring thyroid dysfunction. We evaluate thyroid test utilization in Northern Alberta in terms of testing patterns, frequencies, and reflex cutpoints. METHODS: This retrospective study analyzed thyroid test requests from January to December 2014. Each request was designated as appropriate or potentially inappropriate as per clinical practice guidelines and Choosing Wisely recommendations, and the frequencies of each testing pattern were calculated. Sub-analysis was performed to categorize testing patterns based on physician specialty. The number of test requests per patient was determined to assess the appropriateness of testing frequency. Receiver operating characteristic (ROC) curves were generated to define optimal TSH cutpoints for automatic reflex to FT4 testing. RESULTS: Of 752,217 test requests, approximately 10% were potentially inappropriate in terms of testing patterns. Free thyroxine (FT4) and free triiodothyronine (FT3) requested with TSH accounted for 59% of all potentially inappropriate test requests, and 49% of requests from endocrinologists (ENDO) were potentially inappropriate, occurring most frequently among those with less experience. Excessive testing frequencies were observed in 869 patients, accounting for 9382 test requests. Adjustment of our TSH reflex cutpoint would significantly increase specificity for identifying a low FT4 without compromising sensitivity. CONCLUSIONS: This study suggests that questionable testing patterns, excessive testing frequencies, and suboptimal reflexive testing cutpoints contribute to inappropriate thyroid test utilization.

Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects.

PURPOSE: Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. METHODS: Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). RESULTS: Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2ß of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. CONCLUSION: The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.

Synthesis and biological evaluation of crown ether fused quinazoline analogues as potent EGFR inhibitors.

Crown ether fused anilinoquinazoline analogues were synthesized as novel epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Representative compounds showed potent and selective EGFR inhibitory activities in an in vitro EGFR kinase assay and an EGFR-mediated intracellular tyrosine phosphorylation assay. The synthesis and preliminary biological, physical, and pharmacokinetic evaluation of these fused quinazoline compounds is reported.