Leiden University Scholary Publications
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A systematic review of antibiotic drug shortages and the strategies employed for managing these shortages
No full textBackground: There is a need to examine the impact of increasingly prevalent antibiotic shortages on patient outcomes and on the emergence and spread of antimicrobial resistance. Objectives: To: (1) assess patterns and causes of shortages; (2) investigate the effect of shortages on health systems and patient outcomes; and (3) identify strategies for forecasting and managing shortages. Data sources: PubMed/MEDLINE, EMBASE, Scopus, and Web of Science. Study eligibility criteria: Studies published in English from January 2000 to July 2023. Participants health care, policy, and strategic teams managing and responding to shortages. Patient populations (adults and children) affected by shortages. Participants: Healthcare workers responding to and populations affected by antibiotic shortages. Interventions: Strategies, policies, and mitigation options for managing and responding to antibiotic drug shortages. Assessment of risk of bias: The methodological quality of included studies was reviewed using the most appropriate tool from Joanna Briggs institute critical appraisal tool for each study design. Methods of data synthesis: Data synthesis was qualitative and quantitative using descriptive statistics. Results: The final analysis included 74 studies (61/74, 82.4% high-income countries). Shortages were most reported for piperacillin-tazobactam (21/74, 28.4%), with most of the reported antibiotics being in the WHO Watch category (27/54, 51%). Frequent cause of shortages was disruption in manufacturing, such as supply of active pharmaceutical ingredients and raw materials. Clinical implications of shortages included increased length of hospital stay, treatment failure after using inferior alternative agents, and a negative impact on antimicrobial stewardship programmes (AMS). Robust economic impact analysis of shortages is unavailable. Successfully reported mitigation strategies were driven by AMS and infectious diseases teams in hospitals. Conclusions: Antibiotic shortages are directly or indirectly driven by economic viability and reliance on single source ingredients. The limited data on clinical outcomes indicates a mixed effect, with some infections becoming more difficult to treat, though there is no robust data on the impact of shortages on antimicrobial resistance. The mitigation strategies to manage shortages rely heavily on AMS teams. Avaneesh Kumar Pandey, Clin Microbiol Infect 2025;31:345 (c) 2024 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).Pharmacolog
Immune responses to SARS-CoV-2 in sub-Saharan Africa and western Europe: a retrospective, population-based, cross-sectional study
No full textBackgroundSARS-CoV-2 has been associated with a higher proportion of asymptomatic infections and lower mortality in sub-Saharan Africa than high-income countries. However, there is currently a lack of data on cellular immune responses to SARS-CoV-2 in people living in Africa compared with people in high-income regions of the world. We aimed to assess geographical variation in peripheral and mucosal immune responses.MethodsIn this retrospective, population-based, cross-sectional study, we analysed peripheral blood and nasal curettage samples from seven clinical studies involving individuals from Senegal (Senegalese cohort), the Netherlands, and Germany (European cohort). Samples were collected between Nov 1, 2018, and Dec 20, 2021. We included samples from individuals with no, mild, or severe COVID-19. A validation cohort of individuals from Senegal and Gabon (n=64) was used to validate key findings from the main cohort. Matching of individuals between geographical regions by age, sex, viral load, and infection severity and duration was used to address confounding factors. We examined the cellular, humoral, and cytokine immune responses using cytometry by time of flight, spectral flow cytometry, ELISA, and Luminex.FindingsWe included 133 individuals (59 from the Senegalese cohort and 74 from the European cohort). In contrast to the European cohort, mild COVID-19 in the Senegalese cohort was not associated with any statistically significant perturbations in blood or nasal immune cell profiles, nor with increased pro-inflammatory cytokines, although SARS-CoV-2-specific adaptive immunity was readily induced, as seen in Europeans. In severe COVID-19, both the Senegalese and European cohorts showed lymphopenia (Senegal: 2·9-times decrease, p=0·0010 vs Europe: 1·6-times decrease, p=0·0046) and increased neutrophil frequencies in blood (Senegal: 2·0-times increase, p=0·0044 vs Europe: 1·3-times increase, p=0·026) and the nasal mucosa CD66b+CD16low neutrophils (Senegal: 9·9-times increase, p=0·045 vs Europe: 392-times increase, pinflammasome activation, or monocyte recruitment to the nasal mucosa.InterpretationThe observed divergent immunological trajectories during SARS-CoV-2 infection offer a potential explanation for the reported attenuated disease course in sub-Saharan Africa and highlight the need to further investigate immune responses to SARS-CoV-2 in understudied populations.Molecular Technology and Informatics for Personalised Medicine and Healt
Balancing boundaries: observed parental autonomy support and psychological control in the context of parent‐adolescent interactions and adolescent depression
No full textEducation and Child Studie
Homochirality in the Vicsek model: fluctuations and potential implications for cellular flocks
No full textTheoretical Physic
Injustice without victims or arguments from generational overlap?: a reply to gosseries on non-identity
No full textAxel Gosseries considers, and partly defends, several strategies to address the non-identity problem (NIP). We engage critically with two strategies endorsed by Gosseries: the severance strategy and the overlap strategy. The latter comprises two different sub-strategies: the containment sub-strategy and the indirect sub-strategy. We believe that severance is less promising than Gosseries suggests. It comes at a high theoretical cost, which is important to acknowledge even if, ultimately, there is reason to pay it. The sub-strategies that comprise the overlap strategy are more promising, and they can justify more in terms of the scope and content of inter-generational justice than Gosseries suggests in his book. Endorsing the overlap strategies is attractive because doing so limits the need for impersonal considerations in theories of inter-generational justice.NWOVI.Veni.191F.002Political Philosophy and Ethic
MIBiG 4.0: advancing biosynthetic gene cluster curation through global collaboration
No full textSpecialized or secondary metabolites are small molecules of biological origin, often showing potent biological activities with applications in agriculture, engineering and medicine. Usually, the biosynthesis of these natural products is governed by sets of co-regulated and physically clustered genes known as biosynthetic gene clusters (BGCs). To share information about BGCs in a standardized and machine-readable way, the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard and repository was initiated in 2015. Since its conception, MIBiG has been regularly updated to expand data coverage and remain up to date with innovations in natural product research. Here, we describe MIBiG version 4.0, an extensive update to the data repository and the underlying data standard. In a massive community annotation effort, 267 contributors performed 8304 edits, creating 557 new entries and modifying 590 existing entries, resulting in a new total of 3059 curated entries in MIBiG. Particular attention was paid to ensuring high data quality, with automated data validation using a newly developed custom submission portal prototype, paired with a novel peer-reviewing model. MIBiG 4.0 also takes steps towards a rolling release model and a broader involvement of the scientific community. MIBiG 4.0 is accessible online at https://mibig.secondarymetabolites.org/.Microbial Biotechnolog
Molecular properties of the RmlT wall teichoic acid rhamnosyltransferase that modulates virulence in Listeria monocytogenes
No full textWall teichoic acids (WTAs) from the major Gram-positive foodborne pathogen Listeria monocytogenes are peptidoglycan-associated glycopolymers decorated by monosaccharides that, while not essential for bacterial growth, are required for bacterial virulence and resistance to antimicrobials. Here we report the structure and function of a bacterial WTAs rhamnosyltransferase, RmlT, strictly required for L. monocytogenes WTAs rhamnosylation. In particular, we demonstrated that RmlT transfers rhamnose from dTDP-L-rhamnose to naked WTAs, and that specificity towards TDP-rhamnose is not determined by its binding affinity. Structures of RmlT with and without its substrates showed that this enzyme is a dimer, revealed the residues responsible for interaction with the substrates and that the catalytic residue pre-orients the acceptor substrate towards the nucleophilic attack to the sugar. Additionally, the structures provided indications for two potential interaction pathways for the long WTAs on the surface of RmlT. Finally, we confirmed that WTAs glycosyltransferases are promising targets for next-generation strategies against Gram-positive pathogens by showing that inactivation of the RmlT catalytic activity results in a decreased infection in vivo.Bio-organic Synthesi
New policy tools and traditional policy models: better understanding behavioural, digital and collaborative instruments
No full textThe politics and administration of institutional chang
Integration, demands and accommodations: an exploration of summative assessment practices in Dutch bilingual secondary education
No full textIn content and language integrated learning (CLIL), the goal is to support learning of both subject content and (subject-related) language, through an integrated approach. Based on the principle of constructive alignment (Biggs, 1996), it is logical to assume that such integration carries through to assessment. This study explores the extent to which this is the case in the context of bilingual secondary education in the Netherlands. Drawing on quantitative, self-report data from a teacher questionnaire, and qualitative analysis of assessment materials, we explore the relative roles of language and content, the use of accommodations and translanguaging as support, and the cognitive and linguistic demands posed by assessments. In line with previous research, it appears that assessment practices do not always align with the integrated goals of CLIL. Implications for practice are discussed, as is the need for more attention for this aspect of CLIL in research and teacher education.Teaching and Teacher Learning (ICLON)Language Use in Past and Presen