Insertion sequences (IS) represent mobile genetic elements that have been shown to be associated with bacterial evolution and adaptation due to their effects on genome plasticity. In Bordetella pertussis, the causative agent of whooping cough, the numerous IS elements induce genomic rearrangements and contribute to the diversity of the global B. pertussis population. Previously, we have shown that the majority of IS-specific endogenous promoters induce the synthesis of alternative transcripts and thereby affect the transcriptional landscape of B. pertussis. Here, we describe the regulatory RNA Rfi2, which is transcribed from the Pout promoter of the IS481 gene BP1118 antisense to the adjacent fim2 gene encoding the major serotype 2 fimbrial subunit of B. pertussis. Among the classical bordetellae, Rfi2 is unique to B. pertussis, suggesting its specific role in virulence. We show that Rfi2 RNA attenuates fim2 transcription and, consequently, the production of the Fim2 protein. Interestingly, the mutant that does not produce Rfi2 displayed significantly increased cytotoxicity towards human macrophages compared to the parental strain. This observation suggests that the Rfi2-mediated reduction in cytotoxicity represents an evolutionary adaptation of B. pertussis that fine-tunes its interaction with the human host. Given the immunogenicity of Fim2, we further hypothesize that Rfi2-mediated modulation of Fim2 production contributes to immune evasion. To our knowledge, Rfi2 represents the first functionally characterized IS element-driven antisense RNA that modulates the expression of a virulence gene.

• Keywords
• Bordetella pertussis, antisense RNA, cytotoxicity towards macrophages, fimbriae serotype 2, insertion sequence, modulation of virulence,
• MeSH
• RNA, Antisense * genetics   metabolism   MeSH
• Fimbriae, Bacterial * genetics   metabolism   MeSH
• Bordetella pertussis * genetics   pathogenicity   metabolism   MeSH
• Virulence Factors, Bordetella genetics   MeSH
• Humans MeSH
• Macrophages microbiology   MeSH
• Whooping Cough microbiology   MeSH
• Promoter Regions, Genetic MeSH
• Fimbriae Proteins * genetics   metabolism   MeSH
• Gene Expression Regulation, Bacterial * MeSH
• Serogroup MeSH
• DNA Transposable Elements * MeSH
• Virulence MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Antigens, Bacterial MeSH
• RNA, Antisense * MeSH
• Virulence Factors, Bordetella MeSH
• fim2 protein, Bordetella MeSH Browser
• Fimbriae Proteins * MeSH
• DNA Transposable Elements * MeSH

Plant water use efficiency (WUE) links physiological processes to ecosystem-scale carbon and water cycles, making it a crucial parameter for climate change adaptation modelling. Climate and stratospheric ozone dynamics expose plants to varying intensity of ultraviolet-B radiation (UV-B), which affects stomatal function and transpiration. This meta-analysis evaluates UV-B effects on WUE using gas exchange and isotopic proxies. While UV-B radiation reduces stomatal conductance and transpiration, it also suppresses photosynthesis, particularly under non-saturating light. As a result, WUE remains unchanged or declines in UV-B exposed plants, depending on the measurement method. Instantaneous gas exchange-based WUE proxies indicate a decrease, whereas isotope-based proxies, integrating long-term fluxes, show no significant UV-B effect. The suppression of photosynthesis due to UV-B occurs only when UV-B lamps are used to increase the UV-B dose; when UV-B is excluded under field conditions there is no significant effect on WUE. Only some field studies report improved WUE under ambient UV-B, suggesting potential adaptive benefits. Overall, the findings challenge the assumption that UV-B-induced decreases in transpiration enhance WUE. Instead, they highlight a complex interplay between UV radiation, photosynthesis, and stomatal regulation, emphasizing the need to reconsider UV-B's role in plant water relations under future climate conditions.

• Keywords
• photosynthesis, stable carbon isotopes, stomata, ultraviolet radiation,
• MeSH
• Photosynthesis radiation effects   MeSH
• Climate Change MeSH
• Plant Stomata radiation effects   physiology   MeSH
• Plants * radiation effects   metabolism   MeSH
• Plant Transpiration * radiation effects   physiology   MeSH
• Ultraviolet Rays * MeSH
• Water * metabolism   MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Names of Substances
• Water * MeSH

OBJECTIVES: A number of population pharmacokinetic (popPK) models of imipenem in critically ill patients are available for dosing optimization, but they represent only a narrow range of kidney functions. This study evaluates the target attainment of on-label regimens through popPK modelling and simulation in patients across different kidney functions. METHODS: A popPK model was built based on two datasets from Switzerland (model development population, 151 patients, 322 concentrations) and externally validated on two datasets from the Czech Republic (19 patients, 111 concentrations) and Vietnam (43 patients, 85 concentrations). Monte Carlo simulations were performed to evaluate the probability of target attainment from a MIC of 0.125 mg/L to 32 mg/L. We estimated the cumulative fraction of response against Pseudomonas aeruginosa (the epidemiological cut-off value was 4 mg/L) across a broad range of Cockcroft-Gault creatinine clearance values (CLCRCG 15-130 mL/min). Targets of 40% and 100%ƒT > MIC (percentage of dosing interval estimated free concentrations above MIC) were investigated. RESULTS: Decreased kidney function estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration 2021 (eGFRCKD-EPI <90 mL/min) was observed in 70 of 151 patients (46.4%) within the model development population, and in 11 of 19 (57.9%) and 24 of 43 (55.8%) patients in the Czech Republic and Vietnam, respectively. CLCRCG significantly influenced the imipenem clearance described by a two-compartment model. For probability of target attainment, all regimens achieved 40% ƒT > MIC2mg/L. With a 100%ƒT > MIC target, 500 mg q6h (CLCRCG 30-60 mL/min) could only cover an MIC of up to 1 mg/L, irrespective of infusion time. For cumulative fraction of response, no dosing regimen could cover susceptible P. aeruginosa for 100%ƒT > MIC. DISCUSSION: The highest on-label imipenem dosing regimens failed to attain 100% ƒT > MIC4mg/L in patients with decreased kidney function. Higher dosing may be necessary to cover MIC of 4 mg/L. Future trials should explore their efficacy, toxicity, and the utility of model-informed precision dosing in this population.

• Keywords
• Critical illness, Decreased kidney function, External validation, Imipenem, Population pharmacokinetics, Simulation,
• MeSH
• Anti-Bacterial Agents * pharmacokinetics   administration & dosage   MeSH
• Adult MeSH
• Glomerular Filtration Rate MeSH
• Imipenem * pharmacokinetics   administration & dosage   MeSH
• Critical Illness MeSH
• Middle Aged MeSH
• Humans MeSH
• Monte Carlo Method MeSH
• Microbial Sensitivity Tests MeSH
• Pseudomonas Infections * drug therapy   MeSH
• Pseudomonas aeruginosa drug effects   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Switzerland MeSH
• Vietnam MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• Imipenem * MeSH

Despite the growing number of patients with neurodegenerative diseases, especially Parkinson's disease, and the associated increasing pressure on global healthcare systems, there is still a lack of reliable laboratory methods that allow for the rapid and highly accurate diagnosis of these diseases at a pre-symptomatic or early stage, i.e., before irreversible pathomorphological and functional changes occur. Furthermore, current treatment strategies remain limited to the management of symptoms and fail to address the underlying causes of Parkinson's disease. This diagnostic and therapeutic gap is becoming increasingly critical. Recent advances in metabolomics, fuelled by major improvements in analytical technologies, now offer unprecedented opportunities to identify novel biomarkers and therapeutic targets. In this context, intermediates of tryptophan metabolism, along with dopamine metabolites such as aminochrome, appear to be particularly promising candidates. They include various neurotoxic, neuroprotective, and otherwise bioactive molecules, which are directly involved in regulating nervous system functions and closely interact with neural structures. Aminochrome, for instance, plays a pivotal role in inducing neurodegenerative processes, including the misfolding of α-synuclein, a hallmark of Parkinson's disease. Given the accelerating development of metabolomic platforms and the urgent clinical need for early diagnosis and novel therapeutic strategies, the exploration of metabolite-based biomarkers and targets represents a timely and highly relevant research direction.

• Keywords
• Aminochrome, Biomarkers, Dopamine, Metabolites, Metabolomics, Parkinson's disease, Tryptophan,
• Publication type
• Journal Article MeSH
• Review MeSH

Wounds are a global health challenge that often causes serious consequences in terms of morbidity or mortality. However, good wound dressings should retain their properties for an adequate period to avoid risking the health and lives of patients. Therefore, in this study, we first compared the long-term stability and biological performance of two polysaccharide-based sponges-chitosan- and levan-based-crosslinked with dialdehyde levan synthesized by our team. The composites were stored in a climatic chamber for six months under constant temperature and humidity conditions. After each month, a series of analyses characterizing the physicochemical and biological properties of the composite were performed, evaluating their usefulness for their potential use as wound dressing materials. The results showed that the levan-based sponge maintained its structure for up to 4 months of storage in the climate chamber, while the chitosan-based sponge retained its structure throughout the study period. A slight decrease in physicochemical and biological properties was observed in both cases during this time. However, this decrease did not affect the proper functioning of the composites, suggesting that both materials remain viable for use in wound healing applications. Notably, chitosan-based sponges showed superior long-term stability, making them a more reliable material for extended wound dressing applications.

• Keywords
• Dialdehyde Levan, Polysacharides, Wound dressing materials,
• Publication type
• Journal Article MeSH

Spinocerebellar ataxias (SCA) are rare neurodegenerative diseases affecting the cerebellum and its connections, leading to progressive motor disability and cognitive impairment as part of the cerebellar cognitive affective syndrome. Spatial navigation, cognitive function important for everyday movement, relies on spatial perspective taking-the ability to imagine the environment from different viewpoints. While animal and neuroimaging studies suggest a crucial role of the cerebellum in spatial navigation, research on patients with cerebellar disorders is lacking. This study aimed to investigate perspective taking in patients with SCA and Friedreich ataxia (FRDA) using two tests. The Perspective-Taking/Spatial Orientation Test (PTSOT) was administered to 30 SCA patients, 30 FRDA patients, and 34 healthy controls (HC). In addition, SCA and HC completed the Directional-approach Task and a comprehensive neuropsychological assessment. SCA patients performed significantly worse than HC on both perspective taking tests. FRDA patients performed better than SCA and differed from HC only in a subset of PTSOT measures. Perspective taking performance in SCA was associated with global cognition and multiple cognitive domains but not with cerebellar motor impairment. These findings are of potential clinical relevance, as spatial navigation deficits are known to negatively affect the mobility and independence of the affected individuals. Our findings expand the understanding of cognitive impairments in cerebellar diseases, adding spatial navigation to the spectrum of the cerebellar cognitive affective syndrome.

• Keywords
• Cerebellum, Cognition, Friedreich ataxia, Spatial navigation, Spatial perspective taking, Spinocerebellar ataxia,
• MeSH
• Adult MeSH
• Friedreich Ataxia * physiopathology   psychology   MeSH
• Cognition MeSH
• Cognitive Dysfunction physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Cerebellum physiopathology   MeSH
• Neuropsychological Tests MeSH
• Spatial Navigation * physiology   MeSH
• Spinocerebellar Ataxias * physiopathology   psychology   MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Clinical disability is among the risk factors of a more severe coronavirus disease of 2019 (COVID-19) course in patients with multiple sclerosis (PwMS), but might provide an insensitive reflection of actual tissue pathology. Brain volume loss has emerged as a magnetic resonance imaging (MRI) proxy of neurodegeneration in PwMS. Our main objective was to investigate whether brain volume predicts COVID-19 severity in PwMS. METHODS: Clinical data of PwMS followed at the Belgian National Multiple Sclerosis (MS) Center in Melsbroek are collected in a local database in case of COVID-19 diagnosis. One hundred ninety-eight unique PwMS with a suitable 3D brain MRI available, conducted maximally 24 months before their COVID-19 infection, were included. RESULTS: An unfavorable outcome due to COVID-19 was noted in fourteen PwMS (hospitalization: 7.1 %, death: 0.5 %). Neither global nor regional normalized brain volumes predicted COVID-19 severity. Similar results were obtained in patients fulfilling the criteria for benign MS. Being unprotected by vaccination was the only variable significantly associated with a poor COVID-19 outcome (OR 3.7; CI 1.2-10.2). We observed a significant worsening of Symbol Digit Modality Test performance in PwMS with the lowest (Q4) whole brain volume, as compared to those with the highest (Q1) (2.2 ± 8.5 versus -1.2 ± 9.1; P = 0.037). CONCLUSION: Brain volume does not predict COVID-19 outcome in PwMS, including those with benign MS. Unvaccinated individuals remain susceptible to developing a more severe infection. PwMS with the most profound pre-existing brain atrophy may be at risk for cognitive deterioration after COVID-19.

• Keywords
• Brain volume loss, COVID-19, Multiple sclerosis, Outcome, SDMT,
• MeSH
• COVID-19 * complications   diagnostic imaging   MeSH
• Adult MeSH
• Cognitive Dysfunction * diagnostic imaging   etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Brain * diagnostic imaging   pathology   MeSH
• Multiple Sclerosis * diagnostic imaging   complications   psychology   pathology   MeSH
• SARS-CoV-2 MeSH
• Severity of Illness Index MeSH
• Organ Size MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Belgium MeSH

The escalation of anthropogenic activities contributes to the accumulation of chemicals in life-supporting ecosystems and water reserves, while nearly 80% of the global population faces a high risk of water insecurity. Therefore, advanced nanomaterials for environmental remediation and ecosystem preservation are essential. However, their adoption has been slow, mainly due to the need for water treatment strategies that comply with sustainability criteria. This work showcases the efficient removal of emerging pharmaceutical pollutants from water using functionalized graphenes and the direct upcycling of the used sorbents into electrodes for energy storage, without the need for any intermediate treatment. Remarkably, the performance of the repurposed sorbents as supercapacitor electrodes exceeds that of the parent functionalized graphenes by up to 100% in a full cell device. This enhanced performance and cycling stability are attributed to improved charge transport and redox activity induced by the strong adsorption of the pollutants, as supported by theoretical calculations. The findings open avenues for reclaiming the value of spent sorbents, mitigating the environmental and economic burden of their disposal or regeneration, while fostering sustainable resource management, and energy storage.

• Keywords
• Decontamination, Energy storage, Estrogens, Pharmaceuticals, Repurposing, Supercapacitors, Upcycling,
• Publication type
• Journal Article MeSH

Norovirus is a highly contagious virus and the leading cause of acute gastroenteritis worldwide. The World Health Organization (WHO) estimates that approximately 685 million cases of norovirus infection occur each year, with around 200 million affecting children under the age of five. The impact of this virus is substantial, contributing to roughly 200,000 deaths annually-about 50,000 of which are among young children-mostly in low-income countries. In addition to the human toll, norovirus imposes a significant economic burden, with global costs reaching approximately $60 billion each year due to healthcare expenses and lost productivity. In this paper, we present a fractional-order mathematical analysis of the norovirus epidemic model, focusing on its transmission dynamics, incorporating memory effects. The total population, denoted as N(t), is categorized into four compartments: susceptible, exposed, infected, and recovered. We analytically derive the equilibrium points and the basic reproduction number of the model. Furthermore, we discuss the properties of positivity, boundedness, uniqueness, and existence to ensure the model's validity. The non-linear model is linearized around its equilibrium points, and local stability is analyzed using the eigenvalues of the Jacobian matrix. In addition, global stability is examined using the Lyapunov function and LaSalle's invariance principle. To validate the theoretical findings, a numerical scheme based on the GL-Non-Standard Finite Difference (NSFD) method is developed, which serves to verify the theoretical analysis of the norovirus epidemic model.

• Keywords
• Analytical analysis, Mathematical model, Norovirus, Numerical results, Reproductive number, Sensitive analysis, Stability analysis,
• Publication type
• Journal Article MeSH

Due to ongoing climate change, extreme climatic events are expected to increase in magnitude and frequency. While individual species' responses to thermal extremes are widely studied, the impact of extreme heat events on species interactions and the key functions they provide in communities is understudied. As outcomes of species interactions depend on coordinated physiology and development, the consequences of heat exposure are likely impacted by its timing relative to the organisms' life history traits, but to what extent is unclear. In this study, we evaluate how the timing of heat exposure affects interactions among nine tropical Drosophila-parasitoid species combinations using laboratory microcosm experiments. Interactions were most affected when heat exposure coincided with parasitism, leading to decreased parasitism rates. Parasitism rates also dropped when extreme heat occurred after parasitism in one instance. Experiencing heat exposure before parasitism had little effect. Using a simulation model, we determined that the combined effects of parasitism and heat exposure are generally additive, with no evidence of delayed consequences of heat exposure early in development on parasitism outcomes. Furthermore, we found adult host flies and parasitoids more resistant to heat exposure than their larval stages. Thus, whether more frequent extreme heat events disrupt species interactions globally will depend on their exact timing relative to ontogenetic stages and interactions. Heat exposure impacts the two trophic levels differently. Thus, when heat exposure coincides with parasitism, it may diminish the ability of parasitoids to control their hosts, affecting both natural ecosystems and agricultural environments.

• Keywords
• Climate change, Communities, Host–parasitoid, Ontogeny, Tropical ecology,
• MeSH
• Drosophila * parasitology   MeSH
• Extreme Heat * MeSH
• Host-Parasite Interactions * MeSH
• Climate Change MeSH
• Larva MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH