Leiden University Scholary Publications
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Effectiveness of clindamycin-based exposure strategies in experimental mature staphylococcal biofilms
Get PDFDue to increasing antimicrobial resistance and side effects caused by current standard antimicrobial regimens used for treatment of prosthetic joint infection (PJI), alternative options are urgently needed. We aimed to investigate the effect of clindamycin in different exposure strategies against Staphylococcus aureus in an in vitro mature biofilm model. In short, 7-day biofilms were generated on polystyrene plates and titanium-aluminum-vanadium discs using a clinical S. aureus PJI isolate. Next, biofilms were exposed to clindamycin according to four strategies: single 24-h exposure; prolonged 48- or 72-h exposure; repeated 24-h exposures during a 4-day period, and sequential exposures of initial 24-h rifampicin-based therapy followed by 24-h expo sure to clindamycin. The remaining bacterial load (colony-forming unit [CFU]/mL) after antibiotic exposure was assessed. Confocal laser scanning and atomic force microscopy were applied to evaluate the biofilm structure. Single exposure to clindamycin for 24 h or prolonged up to 72 h did not result in any relevant reduction in bacterial load. Repeated 24-h exposures demonstrated relevant reductions of >3 log CFU/mL at clindamycin concentrations >= 16 mg/L for the 3rd and 4th consecutive doses. Sequential rifampi cin-ciprofloxacin combination exposure followed by clindamycin showed bacterial load reductions of 3- to 4-log CFU/mL, similar to continued rifampicin-ciprofloxacin exposure. This was achieved for concentrations equivalent to levels achieved after standard dosing of clindamycin in clinical practice. These experimental findings support that clindamycin monotherapy is not an optimal choice when starting antimicrobial treatment of PJI but that later on, rifampicin may be safely switched to clindamycin in patients with PJI who do not tolerate prolonged rifampicin-based treatment.Immunogenetics and cellular immunology of bacterial infectious disease
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Get PDFThe Legitimacy and Effectiveness of Law & Governance in a World of Multilevel Jurisdiction
From antiquity to the American war of independence
No full textHistory and International Studies 1900-presen
Gastroesophageal reflux disease is associated with a more severe interstitial lung disease in systemic sclerosis in the EUSTAR cohort
Get PDFObjectivesGastroesophageal reflux disease (GERD) is frequent in systemic sclerosis (SSc) and could predict progression of interstitial lung disease (ILD). We aimed to analyse (1) the prevalence of GERD among SSc-ILD patients, (2) its association with disease characteristics and (3) predictive factors for ILD progression in SSc-ILD patients with GERD.MethodsSSc patients from the EUSTAR database with ILD were included. GERD was labelled as present if reflux/dysphagia was reported at the baseline visit or before. Disease characteristics of patients with and without GERD were compared at baseline. ILD progression was defined as relative FVC decline ≥10% or relative FVC decline between 5–9% in association with relative DLCO decline of ≥15% over 12 ± 3 months of follow-up. Prognostic factors for ILD progression, overall survival and progression-free survival in SSc-ILD patients with GERD were tested by multivariable Cox regression.ResultsA total of 5462 SSc-ILD patients were included, 4400 (80.6%) had GERD. Patients with GERD presented more frequently with diffuse cutaneous SSc (OR: 1.44 [1.22–1.69], P vs 90.2 ± 20.1, P 0.001), lower DLCO (60.8 ± 19.7 vs 65.3 ± 20.6, P 0.001) and worse performance at the 6-min walking test. Female sex (HR: 1.39 [1.07–1.80], P = 0.012) and older age (HR: 1.02 [1.01–1.03], P 0.001) independently predicted ILD progression in SSc-ILD patients with GERD.ConclusionSSc-ILD patients with GERD appear to suffer from a more severe SSc disease. In this population, female sex may be considered a risk factor for ILD progression.Pathophysiology and treatment of rheumatic disease
Bridging planarian bioassays and AOP-based environmental assessment: toward mechanistic insights into pollutant-induced disruptions
No full textHuman activities have introduced a wide range of contaminants into aquatic ecosystems, posing substantial ecological and health risks. Robust bioindicators are essential for accurately predicting these impacts. Since the early 1980s, planarians—freshwater flatworms known for their remarkable regenerative ability and neurologically relevant system—have been used in ecotoxicology, witnessing renewed scientific interest post-2010. This critical review synthesizes and evaluates two decades of research on planarian toxicology, emphasizing behavioral and developmental endpoints upon exposure to metals, pharmaceuticals, pesticides, chemicals, nanomaterials, and biomaterials. Using an ecotoxicological Adverse Outcome Pathway (AOP) framework, we examine toxic mechanisms at the molecular, cellular, tissue/organ, organismal, and population-level. We also highlight recent advances in single-cell omics, metabolomics, and machine learning, and discuss their integration with automated high-throughput screening platforms to improve the predictive capacity of toxicological assessments. These approaches offer opportunities to address complex mixture toxicity and to better link laboratory findings with ecological effects. By combining multi-level biological organization with advanced analytical tools in an ecotoxicological AOP framework, this review provides a novel perspective that bridges classical toxicology with predictive environmental risk assessment, offering clear priorities for methodological standardization and expanded application in environmental monitoring.Environmental Biolog
Exploring reactive interfaces: nanoplastics, catalysts, and 2D materials
No full textThis thesis investigates reactive interfaces in surface science across three domains: heterogeneous catalysis, environmental nanoplastics, and two-dimensional materials. A central achievement is the development of the ReactorAFM/STM, an instrument enabling simultaneous atomic force and scanning tunneling microscopy under elevated pressures and temperatures. Using this setup, catalytic reactions such as Pd(100) oxidation and Fischer–Tropsch synthesis on cobalt nanoparticles were studied under near-industrial conditions, bridging the traditional pressure and materials gaps. To address the challenge of nanoplastic pollution, new laboratory protocols were established for producing and analyzing nanoplastics on well-defined surfaces. Physical vapor deposition is introduced as a controllable route to model environmental degradation and support systematic studies of nanoplastic behavior.Finally, the controlled growth of hexagonal boron nitride (h-BN) on Ni(111) using a novel molecular precursor was investigated through synchrotron-based spectroscopy and microscopy, revealing key aspects of 2D-material formation.Together, these studies demonstrate how advanced microscopy and operando experimentation can reveal processes at surfaces under realistic conditions, contributing to both fundamental science and environmental understanding.Catalysis and Surface Chemistr
Post-interventional vascular remodeling: novel insights and therapeutic strategies
No full textIn this thesis, we employed state-of-the-art techniques to explore the molecular mechanisms underlying the adaptations of blood vessels after vascular surgery / injury using in vivo, ex vivo and in vitro models. Moreover, building on our findings, we explored several therapeutic interventions to improve outcomes of vascular surgery.LUMC / Geneeskund
Learning to swim the endless waves: examining self-management and risk factors for (chronic) depression
No full textAccording to depression treatment guidelines, psychiatric rehabilitation is recommended for patients with difficult-to-treat persistent depressive disorder (PDD) when previous treatments have been insufficient. Addressing this need, this dissertation evaluated a self-management intervention, the Patient and Partner Education Program for All Chronic Diseases – adapted for PDD (PPEP4All-PDD), designed for patients and their informal caregivers. A secondary aim was to enhance understanding of the long-term trajectory and vulnerability factors associated with depression. Findings indicated no significant differences between PPEP4All-PDD and standard care regarding costs or quality of life, aligning with outcomes from previous rehabilitation studies. When examining depression prognosis, we found that over nine-years, recurrence is the expected course, rather than the exception. Additionally, predictors of relapse, cognitive reactivity (CR) emerged as a moderate independent risk factor of recurrence for the first episodes. However, a history of previous episodes was identified as the strongest predictor of future recurrence These insights underscore the importance of early relapse prevention in clinical practice to prevent future chronicity and highlight the need for innovative, accessible rehabilitation strategies, such as online adaptations of PPEP4All. Further research is needed to clarify at which point during the treatment process psychiatric is offered to patients. ZonMw, grant number 843–002-709, Projectleader: I.V.E. CarlierLUMC / Geneeskund
The politics of citizenship: governing religion through refugee control in Lebanon
No full textLebanon, a small Middle Eastern country, with a long history of population movements, has welcomed several migratory flows since 1948 to date and sheltered approximately around 2.8 million refugees in 2023, representing the highest number of refugees per capita worldwide and as much as 10% of the total refugee population in the world. While most of these refugees seem to belong to one religion, managing their presence in Lebanon and their integration within the Lebanese society seems to be challenging, considering the sensitive confessional composition, the consociational concordant-based political system, and the constant power struggle resulting from the political structure in place. The dissertation specifically focuses on the two key elements of the Lebanese case which are concerned with the maintenance of religion and demographical balance, and the management of refugee groups in the context of mobility. The first element is the practical outcome of the adoption of a consociational concordant political system in a society composed of 18 different communities, all of which competing to gain and/or maintain political power, which engenders an increased polarization between these communities and generates institutional paralysis. The second element is the concept of ‘crimmigration’ understood within the ‘governing through dynamics’ as materialized in the Global North scholarship and explored in the context of South-South migration and in light of the Lebanese political structure and sensitive politico-confessional framework. The analysis illustrates that as opposed to what seems to influence policymaking, lawmaking and the governance of migration and refugees in the Global North, in Lebanon, it appears that the close monitoring of demography, and therefore the access to citizenship, is important to maintain political stability, further complicating decision-making over refugee governance in Lebanon.Criminal Justice: Maatschappelijk effectieve strafrechtspleging 2023-202
Touched by technology: automated tactile stimulation in the treatment of apnoea of prematurity
Get PDFOne of the challenges preterm infants face is maintaining a rhythmic and stable breathing pattern to ensure effective gas exchange. Due to the immaturity of both their lungs and brains, they often experience irregular breathing and frequent episodes of apnoea. Although apnoea of prematurity usually resolves with maturation, it can lead to serious consequences, including brain damage, developmental delays, and an increased risk of mortality.Tactile stimulation, such as rubbing the infant’s foot or back, is the most commonly used response to apnea and has been recommended for many years. However, this dissertation shows that it is challenging for caregivers to respond quickly and consistently. Therefore, the overall aim of this dissertation was to investigate whether automated tactile stimulation — enabling immediate intervention — could provide a solution for both patients and caregivers. The findings demonstrate that mechanical stimulation can shorten and prevent apneas, with earlier application proving more effective and requiring lower intensity.Since no automated devices are currently available for clinical use, a novel device was developed and tested, demonstrating clinical feasibility and short-term safety. Together, these studies lay the foundation for further development of automated tactile stimulation devices and highlight the potential of technological innovation to improve neonatal care.BOBBY Neonatal; Chiesi; Chipsoft; Concord Neonatal; Fisher &Paykel
Healthcare; Fritz Stephan GmbH; Monivent AB; SLE Ltd, the Willem Alexander Childrens’
HospitalLUMC / Geneeskund