nd co-authors , William J. Breslin, Gregg D. Cappon, Connie L. Chen, Gary Chmielewski, Luc De Schaepdrijver, Brian Enright, Jennifer E. Foreman, Wafa Harrouk, Kok-Wah Hew, Alan M. Hoberman, Julia Y. Hui, Thomas B. Knudsen, Susan B. Laffan, Susan L. Makris, Matt Martin, Mary Ellen McNerney, Christine L. Siezen, Dinesh J. Stanislaus, Jane Stewart, Kary E. Thompson, Belen Tornesi, Jan Willem Van der Laan, Gerhard F. Weinbauer, Sandra Wood & Aldert H. Piersma
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According to the "membrane sensor" hypothesis, the membrane's physical properties and microdomain organization play an initiating role in the heat shock response. Clinical conditions such as cancer, diabetes and neurodegenerative diseases are all coupled with specific changes in the physical state and lipid composition of cellular membranes and characterized by altered heat shock protein levels in cells suggesting that these "membrane defects" can cause suboptimal hsp-gene expression. Such observations provide a new rationale for the introduction of novel, heat shock protein modulating drug candidates. Intercalating compounds can be used to alter membrane properties and by doing so normalize dysregulated expression of heat shock proteins, resulting in a beneficial therapeutic effect for reversing the pathological impact of disease. The membrane (and lipid) interacting hydroximic acid (HA) derivatives discussed in this review physiologically restore the heat shock protein stress response, creating a new class of "membrane-lipid therapy" pharmaceuticals. The diseases that HA derivatives potentially target are diverse and include, among others, insulin resistance and diabetes, neuropathy, atrial fibrillation, and amyotrophic lateral sclerosis. At a molecular level HA derivatives are broad spectrum, multi-target compounds as they fluidize yet stabilize membranes and remodel their lipid rafts while otherwise acting as PARP inhibitors. The HA derivatives have the potential to ameliorate disparate conditions, whether of acute or chronic nature. Many of these diseases presently are either untreatable or inadequately treated with currently available pharmaceuticals. Ultimately, the HA derivatives promise to play a major role in future pharmacotherapy.
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Deze publicatie presenteert de resultaten van het Smartest Connected Cargo Airport Schiphol (SCCAS)-project: een tweejarig onderzoek naar logistieke innovaties die de concurrentiepositie van Schiphol op de luchtvrachtketen versterken. In dit project hebben KLM Cargo, Schiphol Nederland, Cargonaut, TU Delft en Hogeschool van Amsterdam samen met diverse partijen in de luchtvrachtketen nieuwe inzichten ontwikkeld om het afhandelingsproces op Schiphol te stroomlijnen en de productkwaliteit in temperatuurgevoelige ketens zoals bloemen en farma beter te beheersen.In Europa heeft Schiphol een sterke positie: het is de derde vrachtluchthaven na Frankfurt en Parijs. Door de beperking van het aantal beschikbare slots op Schiphol krijgen andere luchthavens zoals Brussel, Luik en Luxemburg de kans om extra lading aan te trekken. Het is daarom de ambitie van Schiphol zich te ontwikkelen tot de Europese voorkeursluchthaven voor logistiek hoogwaardige goederenstromen zoals e-commerce, farmaceutische producten en bloemen, en zich te onderscheiden door een efficiënt en betrouwbaar afhandelingsproces. Om die positie te bereiken zet Schiphol in op vier concrete innovatiedoelstellingen:- verbetering van transparantie in de keten door het delen van informatie;- inzicht in logistieke prestaties op basis van volledige en betrouwbare data over zendingen;- efficiënte en betrouwbare aan- en afvoer van luchtvrachtzendingen (landside pickup & delivery);- procesverbeteringen in de supply chains van temperatuurgevoelige producten.
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In this presentation a comparison is made between the state of art of healthcare in the Netherlands compared to other European countries. Dutch healthcare is of a high quality, the Netherlands rank among the top in Europe, but in-patient costs are high. Expenditures are now almost 100 billion euros. Therefor the Netherlands are facing quite some challenges: rising costs due to ageing, more chronic diseases, use of medication, long stay care etc and pressure on staff and waiting lists. Fresh brains (students Logistics from BUas) can help to improve healthcare and reduce costs. Lecturers and students work together in projects with the healthcare sector (learning communities) and students do their internship in various healthcare organizations (cure and care). In this presentation two examples of graduation assignments are mentioned. One student did research on the implementation of barcodes on primary packaging of pharmaceuticals, another student did research on reducing the length of stay for patients with a hip fracture. They came with useful recommendations for improving patient safety, patient satisfaction and reducing costs.
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From the article: Abstract Sub-chronic toxicity studies of 163 non-genotoxic chemicals were evaluated in order to predict the tumour outcome of 24-month rat carcinogenicity studies obtained from the EFSA and ToxRef databases. Hundred eleven of the 148 chemicals that did not induce putative preneoplastic lesions in the sub-chronic study also did not induce tumours in the carcinogenicity study (True Negatives). Cellular hypertrophy appeared to be an unreliable predictor of carcinogenicity. The negative predictivity, the measure of the compounds evaluated that did not show any putative preneoplastic lesion in de sub-chronic studies and were negative in the carcinogenicity studies, was 75%, whereas the sensitivity, a measure of the sub-chronic study to predict a positive carcinogenicity outcome was only 5%. The specificity, the accuracy of the sub-chronic study to correctly identify non-carcinogens was 90%. When the chemicals which induced tumours generally considered not relevant for humans (33 out of 37 False Negatives) are classified as True Negatives, the negative predictivity amounts to 97%. Overall, the results of this retrospective study support the concept that chemicals showing no histopathological risk factors for neoplasia in a sub-chronic study in rats may be considered non-carcinogenic and do not require further testing in a carcinogenicity study.
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We read the invited review on sustainable medicines use in clinicalpractice by Adeyeye et al.1and would like to congratulate the authorswith the captivating way in which they used scientific facts combinedwith very practical solutions to convey their call to action. This call isprimarily addressed to the NHS, which the authors suspect will reso-nate with other health systems. While we fully agree with necessityof this top-down approach, we additionally believe that there is muchto be gained by making future prescribers more knowledgeable andaware about the impact they have on planetary health. The articleremains very brief about next generation of healthcare professionalsby quoting the General Medical Council's statement that“newly quali-fied doctors must be able to apply the principles, methods and knowl-edge of population health and the improvement of health andsustainable healthcare to medical practice.”2However, the underlyingquestion—how we effectively train future healthcare professionals inthese attitudes underpinned by knowledge—is not addressed...........
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Global society is confronted with various challenges: climate change should be mitigated, and society should adapt to the impacts of climate change, resources will become scarcer and hence resources should be used more efficiently and recovered after use, the growing world population and its growing wealth create unprecedented emissions of pollutants, threatening public health, wildlife and biodiversity. This paper provides an overview of the challenges and risks for sewage systems, next to some opportunities and chances that these developments pose. Some of the challenges are emerging from climate change and resource scarcity, others come from the challenges emerging from stricter regulation of emissions. It also presents risks and threats from within the system, next to external influences which may affect the surroundings of the sewage systems. It finally reflects on barriers to respond to these challenges. http://dx.doi.org/10.13044/j.sdewes.d6.0231 LinkedIn: https://www.linkedin.com/in/sabineeijlander/ https://www.linkedin.com/in/karel-mulder-163aa96/
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ABSTRACT Introduction Junior doctors are responsible for a substantial number of prescribing errors, and final-year medical students lack sufficient prescribing knowledge and skills just before they graduate. Various national and international projects have been initiated to reform the teaching of clinical pharmacology and therapeutics (CP&T) during undergraduate medical training. However, there is as yet no list of commonly prescribed and available medicines that European doctors should be able to independently prescribe safely and effectively without direct supervision. Such a list could form the basis for a European Prescribing Exam and would harmonise European CP&T education. Therefore, the aim of this study is to reach consensus on a list of widely prescribed medicines, available in most European countries, that European junior doctors should be able to independently prescribe safely and effectively without direct supervision: the European List of Essential Medicines for Medical Education. Methods and analysis This modified Delphi study will recruit European CP&T teachers (expert group). Two Delphi rounds will be carried out to enable a list to be drawn up of medicines that are available in ≥80% of European countries, which are considered standard prescribing practice, and which junior doctors should be able to prescribe safely and effectively without supervision. Ethics and dissemination The study has been approved by the Medical Ethics Review Committee of VU University Medical Center (no. 2020.335) and by the Ethical Review Board of the Netherlands Association for Medical Education (approved project no. NVMO‐ERB 2020.4.8). The European List of Essential Medicines for Medical Education will be presented at national and international conferences and will be submitted to international peer-reviewed journals. It will also be used to develop and implement the European Prescribing Exam.
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Background: Adverse outcome pathway (AOP) networks are versatile tools in toxicology and risk assessment that capture and visualize mechanisms driving toxicity originating from various data sources. They share a common structure consisting of a set of molecular initiating events and key events, connected by key event relationships, leading to the actual adverse outcome. AOP networks are to be considered living documents that should be frequently updated by feeding in new data. Such iterative optimization exercises are typically done manually, which not only is a time-consuming effort, but also bears the risk of overlooking critical data. The present study introduces a novel approach for AOP network optimization of a previously published AOP network on chemical-induced cholestasis using artificial intelligence to facilitate automated data collection followed by subsequent quantitative confidence assessment of molecular initiating events, key events, and key event relationships. Methods: Artificial intelligence-assisted data collection was performed by means of the free web platform Sysrev. Confidence levels of the tailored Bradford-Hill criteria were quantified for the purpose of weight-of-evidence assessment of the optimized AOP network. Scores were calculated for biological plausibility, empirical evidence, and essentiality, and were integrated into a total key event relationship confidence value. The optimized AOP network was visualized using Cytoscape with the node size representing the incidence of the key event and the edge size indicating the total confidence in the key event relationship. Results: This resulted in the identification of 38 and 135 unique key events and key event relationships, respectively. Transporter changes was the key event with the highest incidence, and formed the most confident key event relationship with the adverse outcome, cholestasis. Other important key events present in the AOP network include: nuclear receptor changes, intracellular bile acid accumulation, bile acid synthesis changes, oxidative stress, inflammation and apoptosis. Conclusions: This process led to the creation of an extensively informative AOP network focused on chemical-induced cholestasis. This optimized AOP network may serve as a mechanistic compass for the development of a battery of in vitro assays to reliably predict chemical-induced cholestatic injury.
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Objectives: To understand healthcare professionals' experiences and perceptions of nurses' potential or ideal roles in pharmaceutical care (PC). Design: Qualitative study conducted through semi-structured in-depth interviews. Setting: Between December 2018 and October 2019, interviews were conducted with healthcare professionals of 14 European countries in four healthcare settings: hospitals, community care, mental health and long-term residential care. Participants: In each country, pharmacists, physicians and nurses in each of the four settings were interviewed. Participants were selected on the basis that they were key informants with broad knowledge and experience of PC. Data collection and analysis: All interviews were conducted face to face. Each country conducted an initial thematic analysis. Consensus was reached through a face-to-face discussion of all 14 national leads. Results: 340 interviews were completed. Several tasks were described within four potential nursing responsibilities, that came up as the analysis themes, being: 1) monitoring therapeutic/adverse effects of medicines, 2) monitoring medicines adherence, 3) decision making on medicines, including prescribing 4) providing patient education/information. Nurses' autonomy varied across Europe, from none to limited to a few tasks and emergencies to a broad range of tasks and responsibilities. Intended level of autonomy depended on medicine types and level of education. Some changes are needed before nursing roles can be optimised and implemented in practice. Lack of time, shortage of nurses, absence of legal frameworks and limited education and knowledge are main threats to European nurses actualising their ideal role in PC. Conclusions: European nurses have an active role in PC. Respondents reported positive impacts on care quality and patient outcomes when nurses assumed PC responsibilities. Healthcare professionals expect nurses to report observations and assessments. This key patient information should be shared and addressed by the interprofessional team. The study evidences the need of a unique and consensus-based PC framework across Europe.
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