Modelling of ciprofloxacin killing enhanced by hyperbaric oxygen treatment in Pseudomonas aeruginosa PAO1 biofilms

<div><p>Outline</p><p>In chronic lung infections by <i>Pseudomonas aeruginosa</i> (PA) the bacteria thrive in biofilm structures protected from the immune system of the host and from antibiotic treatment. Increasing evidence suggests that the susceptibility of the bacteria to antibiotic treatment can be significantly enhanced by hyperbaric oxygen treatment. The aim of this study is to simulate the effect of ciprofloxacin treatment in a PAO1 biofilm model with aggregates in agarose when combined with hyperbaric oxygen treatment. This is achieved in a reaction-diffusion model that describes the combined effect of ciprofloxacin diffusion, oxygen diffusion and depletion, bacterial growth and killing, and adaptation of the bacteria to ciprofloxacin. In the model, the oxygen diffusion and depletion use a set of parameters derived from experimental results presented in this work. The part of the model describing ciprofloxacin killing uses parameter values from the literature in combination with our estimates (Jacobs, et al., 2016; Grillon, et al., 2016). Micro-respirometry experiments were conducted to determine the oxygen consumption in the <i>P. aeruginosa</i> strain PAO1. The parameters were validated against existing data from an HBOT experiment by Kolpen <i>et al.</i> (2017). The complete oxygen model comprises a reaction-diffusion equation describing the oxygen consumption by using a Michaelis-Menten reaction term. The oxygen model performed well in predicting oxygen concentrations in both time and depth into the biofilm. At 2.8 bar pure oxygen pressure, HBOT increases the penetration depth of oxygen into the biofilm almost by a of factor 4 in agreement with the scaling that follows from the stationary balance between the consumption term and diffusion term.</p><p>Conclusion</p><p>In the full reaction-diffusion model we see that hyperbaric oxygen treatment significantly increases the killing by ciprofloxacin in a PAO1 biofilm in alignment with the experimental results from Kolpen <i>et al.</i> (Kolpen, et al., 2017; Kolpen, et al. 2016). The enhanced killing, in turn, lowers the oxygen consumption in the outer layers of the biofilm, and leads to even deeper penetration of oxygen into the biofilm.</p></div

Recent Cases: Treaties. Extradition. Receiving Money Knowing It to Have Been Fraudulently Obtained

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History, update, and the baby boom of elephants in 1987 at the Zoological Center, Ramat-Gan, Israel

The Zoological Center, Tel-Aviv Ramat-Gan, Israel, has one of the largest breeding herds of African elephants in captivity. It also has a respectable breeding herd of Asian elephants. At peak population, there was a ponderous total of thirteen African and six Asian elephants in our zoo. Of these, six individuals were bom in 1987. In this article I will describe the background of our herds, the animal quarters, and provide some of our interesting observations on the relationships between the newborn and their relatives, bringing the review up to date, 1998

Hospital centralization and performanced in Denmark - ten years on

Denmark implemented a major reform of the administrative and political structure in 2007 when the previous 13 counties were merged into five new regions and the number of municipalities was reduced from 271 to 98. A main objective was to create administrative units that were large enough to support a hospital structure with few acute hospitals in each region and to centralize specialized care in fewer hospitals. This paper analyses the reorganization of the somatic hospital sector in Denmark since 2007, discusses the mechanisms behind the changes and analyses hospital performance after the reform. The reform emphasized an improved acute service and high quality. The number of acute hospitals was reduced from about 40 to 21 hospitals with joint acute facilities. The restructuring and geographical placement of acute hospitals took place in a democratic process subject to central guidelines and requirements. Since the reform, hospital productivity has increased by more than 2 per cent per year and costs have been stable. While the overall indicators point to a successful reform, it has also been criticized that some people in remote areas feel “left behind” in the economic development and that hospital staff are under increased workload pressure. Concurrent with the centralization of hospitals municipalities strengthened their health service with an emphasis on prevention and health promotion