Assessment of Embryo-Induced Transcriptomic Changes in Hamster Uterus Using RNA-Seq.

BACKGROUND/AIMS: The mouse is widely used as an animal model for studying human embryo implantation. However, the mouse is unique in that both ovarian progesterone and estrogen are critical to implantation, whereas in the majority of species (e.g. human and hamster) implantation can occur in the presence of progesterone alone. METHODS: In this study, we analyzed embryo-induced transcriptomic changes in the hamster uterus during embryo implantation by using RNA-seq. Differentially expressed genes were characterized by bioinformatic analysis. RESULTS: We identified a total of 781 differentially expressed genes, of which 367 genes were up-regulated and 414 genes were down-regulated at the implantation site compared to the inter-implantation site. Functional clustering and gene network analysis highlighted the cell cycle process in uterus upon embryo implantation. By examining of the promoter regions of differentially expressed genes, we identified 7 causal transcription factors. Additionally, through connectivity map (CMap) analysis, multiple compounds were identified to have potential anti-implantation effects due to their ability to reverse embryo-induced transcriptomic changes. CONCLUSION: Our study provides a valuable resource for in-depth understanding of the mechanism underlying embryo implantation.

In Vivo Pharmacodynamic Target Assessment of Eravacycline against Escherichia coli in a Murine Thigh Infection Model.

Eravacycline is a novel fluorocycline antibiotic with potent activity against a broad range of pathogens, including strains with tetracycline and other drug resistance phenotypes. The goal of the studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) parameter and magnitude best correlated with efficacy in the murine thigh infection model. Six Escherichia coli isolates were utilized for the studies. MICs were determined using CLSI methods and ranged from 0.125 to 0.25 mg/liter. A neutropenic murine thigh infection model was utilized for all treatment studies. Single-dose plasma pharmacokinetics were determined in mice after administration of 2.5, 5, 10, 20, 40, and 80 mg/kg of body weight. Pharmacokinetic studies exhibited maximum plasma concentration (Cmax) values of 0.34 to 2.58 mg/liter, area under the concentration-time curve (AUC) from time zero to infinity (AUC0-∞) values of 2.44 to 57.6 mg · h/liter, and elimination half-lives of 3.9 to 17.6 h. Dose fractionation studies were performed using total drug doses of 6.25 mg/kg to 100 mg/kg fractionated into 6-, 8-, 12-, or 24-h regimens. Nonlinear regression analysis demonstrated that the 24-h free drug AUC/MIC (fAUC/MIC) was the PK/PD parameter that best correlated with efficacy (R2 = 0.80). In subsequent studies, we used the neutropenic murine thigh infection model to determine if the magnitude of the AUC/MIC needed for the efficacy of eravacycline varied among pathogens. Mice were treated with 2-fold increasing doses (range, 3.125 to 50 mg/kg) of eravacycline every 12 h. The mean fAUC/MIC magnitudes associated with the net stasis and the 1-log-kill endpoints were 27.97 ± 8.29 and 32.60 ± 10.85, respectively.

Health related quality of life in patients with chronic gastritis and peptic ulcer and factors with impact: a longitudinal study.

BACKGROUND: The assessment of Health Related Quality of Life (HRQOL) has been applied as a significant outcome indicator for patients with chronic diseases. No HRQOL study, however, has looked at HRQOL in patients with chronic gastritis and peptic ulcers. This paper focuses on comparing HRQOL in patients with chronic gastritis and peptic ulcers and examining the factors that influence the HRQOL of such patients. Results can be used for making decisions in clinical trials as well as aiding individual management and preventive care of these diseases. METHODS: The Chinese version of the SF-36 (CSF-36) was administered twice to 244 patients with chronic gastritis and peptic ulcers. Mean scores across the two disease groups were compared using t-tests, change over time was analyzed with paired samples t-tests, and factors predicting HRQOL were investigated using the univariate general linear model. RESULTS: The mean domain scores of patients with chronic gastritis were lower than those for patients with peptic ulcers, with the exception of physical functioning. Both groups had lower HRQOL compared with population norms. Mean domain scores increased after treatment in both groups. HRQOL in patients with these two chronic diseases differed by age, education level, marriage, income, and gender, but their explanatory power was relatively low. CONCLUSION: Quality of life of patients with chronic gastritis was lower than that of patients with peptic ulcers, which was lower than population norms. Quality of life in both patients groups was associated with socio-demographic risk factors.