Search

EPs(R) 7630 is an extract of the root of the South African geranium Pelargonium sidoides. Clinical data have shown that this herbal drug preparation can be used to treat upper respiratory tract infections (URTI). The objective of this study was to investigate the impact of EPs 7630 on group A-streptococci (GAS) adhering to and invading host epithelial cells in vitro. Adhesion was assessed by a flow cytometric adhesion assay using calcein-AM-stained S. pyogenes (DSM 2071) as test organism, and HEp-2 cells and buccal epithelial cells (BEC) as substrata. For cell invasion, HEp-2 cell monolayers were infected with S. pyogenes. Intracellular bacteria were determined using a penicillin/gentamicin-protection assay. EPs 7630 was applied in therapeutically relevant concentrations between 0 and 30 microg/ml in both test systems. Compared to controls, EPs 7630 significantly reduced GAS adhesion to HEp-2 cells in a concentration-dependent manner by up to 46% (p<0.001). This was semi-quantitatively confirmed by fluorescence microscopy. Adhesion kinetics additionally indicated a specific antagonistic effect on GAS adhesion. Pre-treatment of epithelial cells or GAS with EPs 7630 showed that it targets GAS rather than HEp-2 cells. However when using BEC as substrata, GAS adhesion increased 7-fold under the influence of EPs 7630 (p<0.001). In viability assays, HEp-2 suspension contained over 90% vital cells, whereas only 10% of the BEC were viable. EPs 7630 reduced GAS invasion of HEp-2 cells significantly when the data taken at time points 60, 120, and 180 min (p=0.026) were analyzed. In conclusion, EPs 7630 develops complementary anti-infective properties: Firstly, EPs 7630 reduces bacterial adhesion to intact epithelial cells and thus protects the organism from bacterial colonization and infection/super-infection. Secondly, EPs 7630 enhances the attachment of bacteria to decaying BEC. In this way pathogens may be trapped and rendered inactive. Thirdly, the inhibition of GAS invasion of epithelial cells protects the host from microorganisms that may have evaded host defences and antibiotic treatment, and therefore prevents recurrent infections. Thus, our investigations provide a rational basis for the treatment of URTI with EPs 7630. [ABSTRACT FROM AUTHOR]

The Step Pyramid of Djoser in Saqqara, Egypt, is considered the oldest of the seven monumental pyramids built about 4,500 years ago. From transdisciplinary analysis, it was discovered that a hydraulic lift may have been used to build the pyramid. Based on our mapping of the nearby watersheds, we show that one of the unexplained massive Saqqara structures, the Gisr el-Mudir enclosure, has the features of a check dam with the intent to trap sediment and water. The topography beyond the dam suggests a possible ephemeral lake west of the Djoser complex and water flow inside the 'Dry Moat' surrounding it. In the southern section of the moat, we show that the monumental linear rock-cut structure consisting of successive, deep compartments combines the technical requirements of a water treatment facility: a settling basin, a retention basin, and a purification system. Together, the Gisr el-Mudir and the Dry Moat's inner south section work as a unified hydraulic system that improves water quality and regulates flow for practical purposes and human needs. Finally, we identified that the Step Pyramid's internal architecture is consistent with a hydraulic elevation mechanism never reported before. The ancient architects may have raised the stones from the pyramid centre in a volcano fashion using the sediment-free water from the Dry Moat's south section. Ancient Egyptians are famous for their pioneering and mastery of hydraulics through canals for irrigation purposes and barges to transport huge stones. This work opens a new line of research: the use of hydraulic force to erect the massive structures built by Pharaohs., Competing Interests: The authors have read the journal’s policy and have the following competing interests: GM, CG and J-CM are paid employees of The Sicame Group, The Atoutscarto Company and The Verilux Company, respectively. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Landreau et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Evidence-based practice, in conjunction with optimum care quality, improves patients' clinical outcomes. However, its implementation in daily clinical practice continues to present difficulties. The aim of this study was to identify the strategies applied by Advanced Practice Nurses (APNs) to foster adherence to clinical practice guideline recommendations., Methods: An exploratory qualitative study was conducted with six focus groups at three public hospitals belonging to the Balearic Islands Health Care Service (Spain). The study participants were 32 ward nurses and 5 advanced practice nurses working routinely with inpatients at these hospitals. The study was conducted from November 2020 to January 2021, using thematic analysis, based on the COREQ checklist., Results: Four major themes related to the facilitation process were identified either by RNs and APNs: the context of the project, APN contribution to nursing team management, healthcare provision on the ward, and the acquisition and application of knowledge., Conclusions: The APNs adapted their actions to the characteristics and needs of the local context, employing strategies aimed at improving teamwork, healthcare, and knowledge management. Each of these contributions enhanced the sustainability of the changes made., (© 2024. The Author(s).)

Human African trypanosomiasis (HAT), or sleeping sickness, is a neglected tropical disease with current treatments marred by severe side effects or delivery issues. To identify novel classes of compounds for the treatment of HAT, high throughput screening (HTS) had previously been conducted on bloodstream forms of T. b. brucei, a model organism closely related to the human pathogens T. b. gambiense and T. b. rhodesiense. This HTS had identified a number of structural classes with potent bioactivity against T. b. brucei (IC 50  ≤ 10 μM) with selectivity over mammalian cell-lines (selectivity index of ≥10). One of the confirmed hits was an aroyl guanidine derivative. Deemed to be chemically tractable with attractive physicochemical properties, here we explore this class further to develop the SAR landscape. We also report the influence of the elucidated SAR on parasite metabolism, to gain insight into possible modes of action of this class. Of note, two sub-classes of analogues were identified that generated opposing metabolic responses involving disrupted energy metabolism. This knowledge may guide the future design of more potent inhibitors, while retaining the desirable physicochemical properties and an excellent selectivity profile of the current compound class., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)