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Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance using an in vitro resistance development model to gain insights into the underlying molecular resistance mechanisms. Cefiderocol susceptible reference strains ( Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa ) and a clinical Acinetobacter baumannii complex isolate were exposed to increasing cefiderocol concentrations using a high-throughput resistance development model. Cefiderocol susceptibility testing was performed using broth microdilution. Whole-genome sequencing was employed to identify newly acquired resistance mutations. Our in vitro resistance development model led to several clones of strains exhibiting cefiderocol resistance, with MIC values 8-fold to 512-fold higher than initial levels. In total, we found 42 different mutations in 26 genes, of which 35 could be described for the first time. Putative loss-of-function mutations were detected in the envZ , tonB , and cirA genes in 13 out of 17 isolates, leading to a decrease in cefiderocol influx. Other potential resistance mechanisms included multidrug efflux pumps ( baeS , czcS , nalC ), antibiotic-inactivating enzymes ( ampR , dacB ), and target mutations in penicillin-binding-protein genes ( mrcB ). This study reveals new insights into underlying molecular resistance mechanisms against cefiderocol. While mutations leading to reduced influx via iron transporters was the most frequent resistance mechanism, we also detected several other novel resistance mutations causing cefiderocol resistance.

Cow milk is under increased scrutiny due to its environmental impact and ethical considerations concerning animal welfare. At the same time, a rising share of consumers is switching to plant-based milk substitutes (abbreviated “plant milk”). The objective of this study was (1) to analyze the product image of plant milk and cow milk and (2) to compare the motivational structure behind the consumption of both product categories. For this purpose, a quantitative survey with Austrian consumers was carried out to analyze the product image of plant milk in comparison to cow milk (n = 1001). The product image analysis revealed that the product image of cow milk is still much better than that of plant milk. Amongst others, cow milk is considered to be healthier, more natural, and better for bones. Product image valuation was dependent on the (non-)consumption of plant milk. Plant milk consumers evaluated plant milk significantly better; they considered plant milk to be much better digestible and allergy-free. The qualitative study using means-end-chain analysis, with two sub-samples of interviewees (plant milk consumers, n = 30, and cow milk consumers, n = 30), identified different motives for the consumption of cow milk and plant milk. Motives that were only reported from cow milk consumers are the origin of milk and the support of small-scale dairy production of farmers. Motives of plant milk consumers were much more diverse and included animal welfare and sustainability aspects.

The planetary boundaries concept has profoundly changed the vocabulary and representation of global environmental issues. We bring a critical social science perspective to this framework through the notion of societal boundaries and aim to provide a more nuanced understanding of the social nature of thresholds. We start by highlighting the strengths and weaknesses of planetary boundaries from a social science perspective. We then focus on capitalist societies as a heuristic for discussing the expansionary dynamics, power relations, and lock-ins of modern societies that impel highly unsustainable societal relations with nature. While formulating societal boundaries implies a controversial process ‒ based on normative judgments, ethical concerns, and socio-political struggles ‒ it has the potential to offer guidelines for a just, social-ecological transformation. Collective autonomy and the politics of self-limitation are key elements of societal boundaries and are linked to important proposals and pluriverse experiences to integrate well-being and boundaries. The role of the state and propositions for radical alternative approaches to well-being have particular importance. We conclude with reflections on social freedom, defined as the right not to live at others' expense. Toward the aim of defining boundaries through transdisciplinary and democratic processes, we seek to open a dialogue on these issues.