The National University of Rosario (Spanish: Universidad Nacional de Rosario, UNR) is a research public university located in the city of Rosario, province of Santa Fe, Argentina.
The rise of antifungal-resistant yeast and the increasing prevalence of invasive mycoses, particularly those caused by Candida albicans, pose a significant global public health challenge. This is primarily due to the limited availability of new antifungal drugs and the continuous emergence of multidrug-resistant strains. Photodynamic inactivation (PDI) has emerged as a promising strategy to combat drug-resistant yeast and complex fungal infections. A key factor in improving this therapy is the development of novel and well-designed photosensitizers (PS) capable of selectively targeting and effectively inactivating fungal cells. In this context, we designed and synthesized four novel porphyrin derivatives bearing different numbers of fluorocarbon chains and tertiary alkylamino groups. At physiological pH, the tertiary amines are protonated, forming cationic centers and resulting in compounds with distinct degrees of amphiphilicity. Absorption and fluorescence studies in solution and in cell suspensions showed that the spectroscopic properties of the porphyrin chromophore were preserved across all substitution patterns. All tetrapyrrolic compounds were able to generate reactive oxygen species through both type I and type II photodynamic mechanisms, with similar yields. However, in vitro PDI treatments against C. albicans revealed a significant influence of the substitution patterns on photokilling efficiency. The compound with the highest dipolar moment achieved complete eradication of the treated fungal cell suspension at a concentration of 5.0 µM after 30 min of irradiation. Furthermore, the PDI treatments were extended to biofilm studies, in which this compound also retained superior photoinactivation efficiency against yeast cells embedded in biofilms. These findings indicate that modulating the dipolar character influences photokilling efficacy, providing useful insights for the design of amphiphilic porphyrins with antifungal photodynamic activity.
Dexmedetomidine (DEX), a selective alpha-2 adrenergic receptor agonist, is widely used in various surgical settings, including cardiac and general surgeries, for its sedative, analgesic, and neuroprotective properties. Patients undergoing brain surgery are particularly susceptible to postoperative delirium (POD). Given the established benefits of dexmedetomidine in other surgical fields, its potential to mitigate delirium in neurosurgery warrants investigation. A systematic search of PubMed, Embase, Scopus, and Cochrane databases was conducted from inception to January 2025 and updated in April 2025, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk of bias was assessed, and a meta-analysis was performed using Review Manager 5.4.1. Five randomized controlled trials were included, evaluating the efficacy of DEX in preventing POD in adult patients undergoing brain surgery. A total of 646 patients were enrolled, with DEX administered with a loading dose ranging from 0.5 to 1 μg/kg over 10 min, followed by a maintenance infusion rate of 0.1 to 0.5 μg/kg/h during the surgical procedure. The pooled risk ratio (RR) for POD with DEX was 0.47 (95
Existe una vasta área de síntomas y fenómenos que se manifiestan en el organismo, que conciernen tanto a la clínica médica como a la clínica psicoanalítica. Ambas abordan lo patológico a través del síntoma, pero recortan distintos reales y proponen incidencias y tratamientos diferenciales del cuerpo y del goce. En consecuencia, resulta necesario abordar un estudio diferencial de la noción de síntoma, organizado en torno al signo-semiológico y en torno a la letra respectivamente. La clínica psicoanalítica no se opone ni excluye a la clínica médica; sino que por el contrario, la continúa. El psicoanálisis restituye la condición de verdad y de goce del síntoma que el discurso de la ciencia elide. Los saberes hacen sistema y los discursos compiten. No hay intersección posible entre medicina y psicoanálisis sino en el espacio de inconsistencia de saber, del límite del saber de uno y otro.
The rotation graph ℛ(G) is the graph whose vertices correspond to search trees on a graph G, with edges determined by rotation operations. In this paper, we analyze how the structure of a rotation graph changes when certain operations are applied to the underlying graph G. Specifically, we examine the effects of three key operations: adding a pendant vertex, adding a true twin to a vertex, and adding a false twin to a vertex. For each of these operations, we provide a full structural characterization of the new rotation graph. Using these descriptions, we investigate the chromatic number of rotation graphs, identifying conditions under which this parameter remains unchanged. As an application, we show that the chromatic number of the rotation graphs of non-complete threshold graphs (including complete split graphs and star graphs) and complete bipartite graphs is 3.
Copper (Cu) is an essential micronutrient that serves as a cofactor for redox enzymes but becomes toxic when unregulated. In bacteria, while Cu efflux systems are well characterized, mechanisms of Cu import remain poorly understood. Here, we characterize the major facilitator superfamily transporter CuiT (STM1486) as a key Cu importer in Salmonella enterica. Comparative genomics revealed that cuiT is evolutionarily conserved across Enterobacteriaceae, and structural modeling predicts a 12-transmembrane-helix architecture with conserved His, Met, and Cys residues suitable for Cu+ coordination. Functional analyses demonstrated that deletion of cuiT reduces intracellular Cu accumulation, slows Cu uptake kinetics, and diminishes expression of Cu-responsive genes, including copA, cueP, cueO, and golB. Conversely, overexpression of CuiT increases intracellular Cu but sensitizes cells to Cu stress, highlighting the need for tight regulation. Kinetic modeling indicates that CuiT mediates rapid Cu import, supporting larger intracellular Cu pools compared to Pseudomonas influx transporters. These findings position CuiT as a central component of the Salmonella Cu homeostasis network, linking Cu import to transcriptional regulation, redox balance, and stress adaptation. Our work provides mechanistic insights into bacterial Cu acquisition and suggests CuiT and associated pathways as potential targets for antimicrobial strategies.
