A nanoparticle platform for combined mucosal healing and immunomodulation in inflammatory bowel disease treatment

Current treatments for inflammatory bowel disease (IBD) treatment consist of anti-inflammatory products. In this study, we sought to induce the physiological secretion of glucagon-like peptide 2, a peptide with intestinal growth-promoting activity, via nanoparticles while simultaneously providing with immunomodulation by tailoring the nanoparticle surface. To this end, we developed hybrid lipid hyaluronate-KPV conjugated nanoparticles loaded with teduglutide for combination therapy in IBD. The nanocarriers induced (or did not induce) immunosuppression depending on the presence (or absence) of a hyaluronan-KPV functionalization. This strategy holds promise as a nanoparticle platform for combined mucosal healing and immunomodulation in IBD treatment

EnergyScope Pathway: An open-source model to optimise the energy transition pathways of a regional whole-energy system

Due to the imperative nature of addressing climate change, the energy transition is currently underway, prompting the recognition of its urgency. Energy system optimisation models have emerged as crucial tools to assist policymakers in formulating laws and regulations that facilitate the transition towards carbon neutrality. While numerous models have been developed to explore various scenarios and define long-term objectives, only a few models focus on optimising the specific pathway to achieve these objectives. Many existing models lack the necessary time resolution to capture the integration of intermittent renewable energies; or are not open-source, creating a challenge in terms of transparency and reproducibility. This paper introduces EnergyScope Pathway, an open-source and documented model that addresses these limitations. It specifically optimises investment strategies for the whole-energy system over a 30-year period, or more, and optimising its hourly operation. This approach allows for a comprehensive evaluation of the effective integration of intermittent renewable energy sources. The model has a concise and efficient formulation, enabling its execution on personal laptops within approximately 15 min. By applying the model to the case study of Belgium, which presents challenges due to limited potential for renewable energy, we illustrate the importance of four pillars: energy efficiency, renewable energies, sector coupling, electrification and imports. The result pave the way to a new and incremental tool to support decision makers. In comparison to non open-source models, we verified the model’s results with similar studies and found consistency in terms of technico-economic estimations

Activated carbon functionalized with amine sites as an efficient alternative for gold thiosulfate recovery

Thiosulfate is a non-toxic and efficient leaching agent that could be employed instead of cyanide for extracting gold from ores. Nevertheless, it is not commonly used in the gold mining industry due to the challenge that represents the recovery of the formed gold thiosulfate complex from the leachate. Several alternatives such as precipitation methods and adsorption onto amine-rich resins have been attempted for solving this problem. However, neither of them have been proven fully effective or compatible with current hydrometallurgical processes. In this research, the functionalization of granular active carbon with covalently grafted primary and quaternary amine sites is proposed, for enhancing its ability at trapping Au thiosulfate. The functionalized carbons accomplish up to 100 % Au recovery (pristine carbon recovers 86%). In-depth solid characterization techniques (XPS, TOF-SIMS, FTIR, PXRD) have revealed that the adsorption mechanism of Au thiosulfate onto amine groups depends on the pH of the solution: at acid pH, an ion exchange mechanism seems to be the dominant process. Under basic conditions, the formation of Au⁰ species is evidenced, in addition to ion-exchange phenomena. Elution of the gold loaded samples has been achieved with a yield up to 76 % with Na₂S₂O₃ and NaCl solutions

Towards a better detection of patients at-risk of linezolid toxicity in clinical practice: a prospective study in three Belgian hospital centers

Linezolid is a last-resort antibiotic for infections caused by multidrug-resistant microorganisms. It is widely used for off-label indications and for longer than recommended treatment durations, exposing patients at higher risk of adverse drug reactions (ADRs), notably thrombocytopenia. This study aimed to investigate ADR incidence and risk factors, identify thrombocytopenia-related trough levels based on treatment duration, and evaluate the performance of predictive scores for ADR development. Adult in-and outpatients undergoing linezolid therapy were enrolled in three hospitals and ADRs and linezolid trough levels prospectively monitored over time. A population pharmacokinetic (pop-PK model) was used to estimate trough levels for blood samples collected at varying times. A multivariate analysis based on 63 treatments identified treatment duration ≥ 10 days and trough levels > 8 mg/L as independent risk factors of developing thrombocytopenia, with high trough values correlated with impaired renal function. Five patients treated for > 28 days did not develop thrombocytopenia but maintained trough values in the target range (< 8 mg/L). The Buzelé predictive score, which combines an age-adjusted Charlson comorbidity index with treatment duration, demonstrated 77% specificity and 67% sensitivity to predict the risk of ADR. Thus, our work supports the necessity of establishing guidelines for dose adjustment in patients with renal insufficiency and the systematic use of TDM in patients at-risk in order to keep trough values ≤ 8 mg/L. The Buzelé predictive score (if ≥ 7) may help to detect these at-risk patients, and pop-PK models can estimate trough levels based on plasma samples collected at varying times, reducing the logistical burden of TDM in clinical practice

Jobflow: Computational Workflows Made Simple

We present Jobflow, a domain-agnostic Python package for writing computational workflows tailored for high-throughput computing applications. With its simple decorator-based approach, functions and class methods can be transformed into compute jobs that can be stitched together into complex workflows. Jobflow fully supports dynamic workflows where the full acyclic graph of compute jobs is not known until runtime, such as compute jobs that launch other jobs based on the results of previous steps in the workflow. The results of all Jobflow compute jobs can be easily stored in a variety of filesystem- and cloud-based databases without the data storage process being part of the underlying workflow logic itself. Jobflow has been intentionally designed to be fully independent of the choice of workflow manager used to dispatch the calculations on remote computing resources. At the time of writing, Jobflow workflows can be executed either locally or across distributed compute environments via an adapter to the FireWorks package, and Jobflow fully supports the integration of additional workflow execution adapters in the future

Does Democracy Inevitably Lead to Aggressive Redistribution? A Family Perspective

This paper explains why democracies marked by inequalities may not experience aggressive redistribution through the lens of parent-child interactions. Parental concerns about the negative impacts of high taxation on their children’s motivation to study and pursue high-paying careers deter the poor majority from harboring an inclination to expropriate the rich. We construct an overlapping generations model in which workers vote on the redistributive policy under majority rule, while considering the incentive costs that the policy imposes on their children. We analyze the stationary Markov perfect equilibrium where the likelihood that a moderate income tax can be credibly enforced increases with the degree of parental altruism. In an extended model where career prospects are jointly determined by study efforts and received educational resources, we provide an analytical and numerical characterization of the conditions under which full redistribution does not materialize in the steady state under both private and public school systems

Prise en charge de la maladie d’Addison : Réflexion sur le rôle du pharmacien d’officine

Résumé : Introduction : La maladie d’Addison est une maladie rare. La base de son traitement repose sur la prise chronique de glucocorticoïdes et de minéralocorticoïdes à vie. Ce traitement doit être adapté à l’initiative du patient lors des situations de stress comme un stress physique intense ou des vomissements. Une mauvaise adaptation du traitement peut entrainer une insuffisance surrénalienne aiguë qui peut être mortelle pour le patient si elle n’est pas prise en charge rapidement. C’est pourquoi l’éducation thérapeutique est primordiale dans la gestion de cette maladie. Objectifs : Déterminer la connaissance des patients vis-à-vis de leur traitement et de son adaptation ainsi que le rôle du pharmacien d’officine dans l’accompagnement des patients ayant la maladie d’Addison. Méthodes : Un questionnaire en ligne de 45 questions a été créé et envoyé en novembre 2023 aux patients de l’association Addison Café. L’analyse descriptive des données a été réalisée à l’aide de statistiques descriptives. La comparaison des données entre les différents groupes a été faite à l’aide des tests de Student, Wilcoxon-Mann-Whitney, Kruskal Wallis, du Khi-carré ou du test exact de Fisher. Résultats : 38 personnes ont répondu à notre questionnaire. La moyenne d’âge des patients est de 54,4 ans et 68,4% sont des femmes. 31,6% des patients déclarent oublier leur médication au moins une fois par mois et 7,9% des patients n’adaptent jamais leur traitement dans les situations de stress. Par ailleurs, 36,8% des patients ne possèdent pas de trousse d’urgence et seulement 15,8% des patients se sentent capable de se faire une injection d’urgence en cas d’insuffisance surrénalienne aiguë. Conclusion : Les patients ayant la maladie d’Addison ont des lacunes dans la connaissance de leur maladie et de leur traitement qui pourraient être comblées par une éducation thérapeutique approfondie dans laquelle le pharmacien pourrait jouer un rôle. Abstract: Introduction: Addison's disease is a rare disorder, and the basis of treatment is lifelong chronic glucocorticoid and mineralocorticoid therapy. This treatment must be adapted on the patient's own initiative in stressful situations, such as intense physical stress or vomiting. Inappropriate treatment can lead to adrenal crisis, which can be fatal for the patient if not promptly managed. This is why therapeutic education is paramount in the management of this disease. Objectives: To determine patients' knowledge of their treatment and its adaptation, and the role of the pharmacist in supporting patients with Addison's disease. Methods: A 45-question online questionnaire was created and sent in November 2023 to patients of the Addison Café association. Descriptive statistics were used to describe the data. Comparison of data between different groups was made using Student's, Wilcoxon-Mann-Whitney, Kruskal Wallis, Chi-square or Fisher's exact test, whichever was appropriate. Results: 38 patients answered our questionnaire. The average age of the patients was 54.4 years, and 68.4% were women. 31.6% of patients reported forgetting their medication at least once a month, and 7.9% of patients never adjusted their medication in stressful situations. Furthermore, 36.8% of patients do not own an emergency kit, and only 15.8% of patients are able to give themselves an emergency injection in the event of a crisis. Conclusion: Patients with Addison's disease had gaps in their knowledge of their disease and treatment that could be filled by in-depth therapeutic education in which the pharmacist could play a role

Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD

Background & Aims Liver homeostasis is ensured in part by time-of-day-dependent processes, many of them being paced by the molecular circadian clock. Liver functions are compromised in metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), and clock disruption increases susceptibility to MASLD progression in rodent models. We therefore investigated whether the time-of-day-dependent transcriptome and metabolome are significantly altered in human steatotic and MASH livers. Methods Liver biopsies, collected within an 8 h-window from a carefully phenotyped cohort of 290 patients and histologically diagnosed to be either normal, steatotic or MASH hepatic tissues, were analyzed by RNA sequencing and unbiased metabolomic approaches. Time-of-day-dependent gene expression patterns and metabolomes were identified and compared between histologically normal, steatotic and MASH livers. Results Herein, we provide a first-of-its-kind report of a daytime-resolved human liver transcriptome-metabolome and associated alterations in MASLD. Transcriptomic analysis showed a robustness of core molecular clock components in steatotic and MASH livers. It also revealed stage-specific, time-of-day-dependent alterations of hundreds of transcripts involved in cell-to-cell communication, intracellular signaling and metabolism. Similarly, rhythmic amino acid and lipid metabolomes were affected in pathological livers. Both TNFα and PPARγ signaling were predicted as important contributors to altered rhythmicity. Conclusion MASLD progression to MASH perturbs time-of-day-dependent processes in human livers, while the differential expression of core molecular clock components is maintained. Impact and implications This work characterizes the rhythmic patterns of the transcriptome and metabolome in the human liver. Using a cohort of well-phenotyped patients (n = 290) for whom the time-of-day at biopsy collection was known, we show that time-of-day variations observed in histologically normal livers are gradually perturbed in liver steatosis and metabolic dysfunction-associated steatohepatitis. Importantly, these observations, albeit obtained across a restricted time window, provide further support for preclinical studies demonstrating alterations of rhythmic patterns in diseased livers. On a practical note, this study indicates the importance of considering time-of-day as a critical biological variable which may significantly affect data interpretation in animal and human studies of liver diseases