Genetic Reconstruction of Protozoan rRNA Decoding Sites Provides a Rationale for Paromomycin Activity against Leishmania and Trypanosoma

Aminoglycoside antibiotics target the ribosomal decoding A-site and are active against a broad spectrum of bacteria. These compounds bind to a highly conserved stem-loop-stem structure in helix 44 of bacterial 16S rRNA. One particular aminoglycoside, paromomycin, also shows potent antiprotozoal activity and is used for the treatment of parasitic infections, e.g. by Leishmania spp. The precise drug target is, however, unclear; in particular whether aminoglycoside antibiotics target the cytosolic and/or the mitochondrial protozoan ribosome. To establish an experimental model for the study of protozoan decoding-site function, we constructed bacterial chimeric ribosomes where the central part of bacterial 16S rRNA helix 44 has been replaced by the corresponding Leishmania and Trypanosoma rRNA sequences. Relating the results from in-vitro ribosomal assays to that of in-vivo aminoglycoside activity against Trypanosoma brucei, as assessed in cell cultures and in a mouse model of infection, we conclude that aminoglycosides affect cytosolic translation while the mitochondrial ribosome of trypanosomes is not a target for aminoglycoside antibiotics

Re-evaluation of acetic acid, lactic acid, citric acid, tartaric acid, mono- and diacetyltartaric acid, mixed acetic and tartaric acid esters of mono- and diglycerides of fatty acids (E 472a-f) as food additives

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The management of children with bronchiolitis in the Australasian hospital setting: Development of a clinical practice guideline

© 2018 The Author(s). Background: Bronchiolitis is the commonest respiratory infection in children less than 12 months and cause of hospitalisation in infants under 6 months of age in Australasia. Unfortunately there is substantial variation in management, despite high levels of supporting evidence. This paper reports on the process, strengths and challenges of the hybrid approach used to develop the first Australasian management guideline relevant to the local population. Method: An adaption of the nine steps recommended by the National Health and Medical Research Council (NHMRC) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology were utilised. Following establishment of the Guideline Development Committee (GDC), we identified the population, intervention, comparator, outcomes and time of interest (PICOt) questions, undertook a systematic literature search and graded the evidence and recommendations using the NHMRC and GRADE processes. Using Nominal Group Techniques (NGT), consensus was sought in formulating the clinical practice recommendations and practice points. Key health professional bodies were consulted to ensure relevance in the Australasian emergency and ward settings. Results: From 33 PICOT questions, clinical recommendations for practice that were deemed relevant to the Australasian population were identified. Specific considerations for the management of Australian and New Zealand indigenous infants in relation to the use of azithromycin and risk factors for more serious illness are included. Using NGT, consensus demonstrated by a median Likert score > 8 for all recommendations was achieved. The guideline presents clinical guidance, followed by the key recommendations and evidence review behind each recommendation. Conclusion: Developing evidence-based clinical guidelines is a complex process with considerable challenges. Challenges included having committee members located over two countries and five time zones, large volume of literature and variation of member's knowledge of grading of evidence and recommendations. The GRADE and NHMRC processes provided a systematic and transparent approach ensuring a final structure including bedside interface, and a descriptive summary of the evidence base and tables for each key statement. Involvement of stakeholders who will ultimately be end-users as members of the GDC provided valuable knowledge. Lessons learnt during this guideline development process provide valuable insight for those planning development of evidence-based guidelines

Scientific opinion on the tolerable upper intake level for manganese

Funding Information: The Panel wishes to thank for their contribution to this output: the WG on Upper Levels: Peter Aggett, Brandy Beverly, Torsten Bohn, Julia Bornhorst, Marta Crous-Bou, Francesco Cubadda, Aymeric Dopter, Susan Fairweather-Tait, Rex FitzGerald, Susan Lanham New, Georg Lietz, Harry J McArdle, Anne Molloy, Giovanni Passeri, Kristina Pentieva, Marco Vinceti and Misha Vrolijk; hearing expert: Peter Willatts, individual scientific advisor (ISA) expert: Keyvin Darney and EFSA staff members: Constanza De Matteu Monteiro, Jean-Lou Dorne, Alessandra Giarola, Irene Muñoz Guajardo, Nena Karavasiloglou, Laura Ciccolallo, Roanne Marie Saad, Angeliki Sofroniou and Silvia Valtueña Martínez. The Panel also wishes to thank Carmen Peláez for her contribution as member of the NDA Panel until June 2023. The Panel acknowledges Thorhallur I Halldorsson, Bryndis Eva Birgisdottir, Anete Dudele, Jacob Juel Christensen and Birna Thorisdottir for the preparatory work as part of a procurement procedure. The Panel also wishes to acknowledge the contribution of all national institutions in European countries that provided consumption data for this scientific output. Publisher Copyright: © 2023 European Food Safety Authority. EFSA Journal published by Wiley-VCH GmbH on behalf of European Food Safety Authority.Peer reviewe

The role of collaboration in the UK green supply chains: an exploratory study of the perspectives of suppliers, logistics and retailers

Many companies around the world have started to realise that working alone will not be sufficient in their move towards a greener supply chain (SC). More specifically, recent UK government regulations on implementing strict CO2 reduction encourage SC operators to work collaboratively, in production and logistics or other operations, to achieve their green objectives. In this research, we look at some underlying factors of SC collaboration, focussing on suppliers, logistics and retailers, for the purpose of improving the environmental sustainability of companies’ SCs. To facilitate our study, we conduct case studies in two overseas supplier companies with the aim of providing a better understanding of how green issues imposed by European and UK customers influence the companies’ actions to meet agreed environmental goals. Based on the initial analysis of the case studies, we develop a conceptual framework which indicates that SC collaboration plays an important role in ensuring companies achieve environmental sustainability of their SCs. Subsequently, staff in middle-management and related roles in sixteen companies operating in the UK are interviewed. This allows us to understand their business practices in terms of SC collaboration with their suppliers and buyers to achieve the goal of CO2 reduction. Finally, drawing upon the information from company reports and websites, a number of UK leading retailers’ actions to reduce CO2 emissions are investigated. We develop a conceptual framework of SC collaboration for environmental sustainability to help companies improve their level of collaboration between suppliers and buyers in terms of meeting their environmental objectives. The proposed framework will serve as a base model for the companies using or considering SC collaboration to achieve their environmental agendas, in line with governmental green regulatory requirements

Simulation suggests that rapid activation of social distancing can arrest epidemic development due to a novel strain of influenza

<p>Abstract</p> <p>Background</p> <p>Social distancing interventions such as school closure and prohibition of public gatherings are present in pandemic influenza preparedness plans. Predicting the effectiveness of intervention strategies in a pandemic is difficult. In the absence of other evidence, computer simulation can be used to help policy makers plan for a potential future influenza pandemic. We conducted simulations of a small community to determine the magnitude and timing of activation that would be necessary for social distancing interventions to arrest a future pandemic.</p> <p>Methods</p> <p>We used a detailed, individual-based model of a real community with a population of approximately 30,000. We simulated the effect of four social distancing interventions: school closure, increased isolation of symptomatic individuals in their household, workplace nonattendance, and reduction of contact in the wider community. We simulated each of the intervention measures in isolation and in several combinations; and examined the effect of delays in the activation of interventions on the final and daily attack rates.</p> <p>Results</p> <p>For an epidemic with an R₀value of 1.5, a combination of all four social distancing measures could reduce the final attack rate from 33% to below 10% if introduced within 6 weeks from the introduction of the first case. In contrast, for an R₀of 2.5 these measures must be introduced within 2 weeks of the first case to achieve a similar reduction; delays of 2, 3 and 4 weeks resulted in final attack rates of 7%, 21% and 45% respectively. For an R₀of 3.5 the combination of all four measures could reduce the final attack rate from 73% to 16%, but only if introduced without delay; delays of 1, 2 or 3 weeks resulted in final attack rates of 19%, 35% or 63% respectively. For the higher R₀values no single measure has a significant impact on attack rates.</p> <p>Conclusion</p> <p>Our results suggest a critical role of social distancing in the potential control of a future pandemic and indicate that such interventions are capable of arresting influenza epidemic development, but only if they are used in combination, activated without delay and maintained for a relatively long period.</p