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Background: In 2013, Turkey introduced one-dose universal varicella vaccination (UVV) at 12 months of age. Inclusion of a second dose is being considered., Methods: We developed a dynamic transmission model to evaluate three vaccination strategies: single dose at 12 months (1D) or second dose at either 18 months (2D-short) or 6 years of age (2D-long). Costs and utilization were age-stratified and separated into inpatient and outpatient costs for varicella and herpes zoster (HZ). We ran the model including and excluding HZ-related costs and impact of exogenous boosting., Results: Five years post-introduction of UVV (1D), the projected varicella incidence rate decreases from 1,674 cases pre-vaccine to 80 cases/100,000 person-years. By 25 years, varicella incidence equilibrates at 39, 12, and 16 cases/100,000 person-years for 1D, 2D-short, and 2D-long strategies, respectively, using a highly effective vaccine. With or without including exogenous boosting impact and/or HZ-related costs and health benefits, the 1D strategy is least costly, but 2-dose strategies are cost-effective considering a willingness-to-pay threshold equivalent to the gross domestic product. The model predicted a modest increase in HZ burden during the first 20-30 years, after which time HZ incidence equilibrates at a lower rate than pre-vaccine., Conclusions: Our findings support adding a second varicella vaccine dose in Turkey, as doing so is highly cost-effective across a wide range of assumptions regarding the burden associated with varicella and HZ disease., Competing Interests: This work was funded by Merck Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, which manufactures vaccines for both varicella (Varivax and ProQuad) and HZ (Zostavax). Lara J. Wolfson, Vincent J. Daniels, and Matthew Pillsbury are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and stockholders of Merck & Co., Inc., Kenilworth, NJ, USA. Zafer Kurugöl has received consulting fees from MSD Turkey. Cuneyt Yardimci was an employee of MSD Turkey, Istanbul, Turkey, at the time of the study. Jeffrey Kyle is an employee of Atlas Data Systems, Berkeley Heights, NJ, USA. Ener Cagri Dinleyici has received consulting fees from MSD Turkey. Employees of the funders participated in the study design, in the analysis and interpretation of the data, in the preparation of the manuscript, and in the decision to submit the manuscript for publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The Notch signaling pathway is involved in cell proliferation and differentiation, and has been recognized as an active pathway in regenerating tissue and cancerous cells. Notch signaling inhibition is considered a viable approach to the treatment of a variety of conditions including colorectal cancer, pancreatic cancer, breast cancer and metastatic melanoma. The discovery that the b-annulated dihydropyridine FLI-06 (1) is an inhibitor of the Notch pathway with an EC50 ≈ 2.5 μM prompted us to screen a library of related analogs. After structure activity studies were conducted, racemic compound 7 was identified with an EC50 = 0.36 μM. Synthesis of individual enantiomers provided (+)-7 enantiomer with an EC50 = 0.13 μM, or about 20-fold the potency of 1., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The purpose of this study was to determine the effects of whole-body electromagnetic field (EMF) exposure on growth plates in growing male rats. Two groups of rats were exposed to either 900 MHz EMF or 1800 MHz EMF 2 h/day for 90 days. Sham control rats were kept under similar conditions without exposure to the EMF. The rats in the EMF group experienced a more rapid weight gain and increase in length (p < 0.05). Calcium, growth hormone, estradiol and testosterone levels in the EMF groups were higher (p < 0.05). The Safranin O staining density of femoral growth plate was lowest in the reserve zone of rats exposed to 1800 MHz and was increased in the proliferative zone of the control group (p < 0.05). The trabecular zone was thinnest among all zones and the reserve and proliferative zones were thicker (p < 0.05) than other zones in 1800 MHz group.In conclusion, 1800 MHz and 900 MHz EMF may cause prolong the growth phase in growing rats.