Unveiling Novel ERCC1-XPF Complex Inhibitors: Bridging the Gap from In Silico Exploration to Experimental Design.

Modifications in DNA repair pathways are recognized as prognostic markers and potential therapeutic targets in various cancers, including non-small cell lung cancer (NSCLC). Overexpression of ERCC1 correlates with poorer prognosis and response to platinum-based chemotherapy. As a result, there is a pressing need to discover new inhibitors of the ERCC1-XPF complex that can potentiate the efficacy of cisplatin in NSCLC. In this study, we developed a structure-based virtual screening strategy targeting the inhibition of ERCC1 and XPF interaction. Analysis of crystal structures and a library of small molecules known to act against the complex highlighted the pivotal role of Phe293 (ERCC1) in maintaining complex stability. This residue was chosen as the primary binding site for virtual screening. Using an optimized docking protocol, we screened compounds from various databases, ultimately identifying more than one hundred potential inhibitors. Their capability to amplify cisplatin-induced cytotoxicity was assessed in NSCLC H1299 cells, which exhibited the highest ERCC1 expression of all the cell lines tested. Of these, 22 compounds emerged as promising enhancers of cisplatin efficacy. Our results underscore the value of pinpointing crucial molecular characteristics in the pursuit of novel modulators of the ERCC1-XPF interaction, which could be combined with cisplatin to treat NSCLC more effectively.

Emerging Approaches for Mitigating Biofilm-Formation-Associated Infections in Farm, Wild, and Companion Animals.

The importance of addressing the problem of biofilms in farm, wild, and companion animals lies in their pervasive impact on animal health and welfare. Biofilms, as resilient communities of microorganisms, pose a persistent challenge in causing infections and complicating treatment strategies. Recognizing and understanding the importance of mitigating biofilm formation is critical to ensuring the welfare of animals in a variety of settings, from farms to the wild and companion animals. Effectively addressing this issue not only improves the overall health of individual animals, but also contributes to the broader goals of sustainable agriculture, wildlife conservation, and responsible pet ownership. This review examines the current understanding of biofilm formation in animal diseases and elucidates the complex processes involved. Recognizing the limitations of traditional antibiotic treatments, mechanisms of resistance associated with biofilms are explored. The focus is on alternative therapeutic strategies to control biofilm, with illuminating case studies providing valuable context and practical insights. In conclusion, the review highlights the importance of exploring emerging approaches to mitigate biofilm formation in animals. It consolidates existing knowledge, highlights gaps in understanding, and encourages further research to address this critical facet of animal health. The comprehensive perspective provided by this review serves as a foundation for future investigations and interventions to improve the management of biofilm-associated infections in diverse animal populations.

Gobernanza de la salud digital: el arte de la transformación de los sistemas de salud / Governance for Digital Health The art of health systems transformation

La incorporación de las tecnologías de la información y de la comunicación a la cadena de valor del sistema de salud supone su transformación digital. Esta transformación exige una gobernanza que incluye aspectos de derechos, normas, responsabilidades y riesgos en áreas como Internet y salud; utilización de los datos de salud; y sistemas de información. La gobernanza de la salud digital se dirige a la mejora de la calidad, la eficiencia y la efectividad del sistema de salud. La triple carga de morbilidad, enfermedades no transmisibles, enfermedades infecciosas y factores externos; la sostenibilidad fiscal y financiera; y la necesidad de mejora de la efectividad y calidad de la atención médica exigen profundos cambios del sistema de salud que hacen imprescindible su transformación digital. El presente documento presenta un marco y una discusión acerca de como pensar e implementar esquemas de Gobernanza para la salud digital. El documento esta orientado a tomadores de decisión en diferentes niveles y sectores de Gobierno

The digital transformation of the health system is achieved by incorporating information and communication technologies into its value chain. This transformation requires governance that addresses rights, regulations, responsibilities, and risks in areas such as internet and health; using health data; and information systems. The aim of digital health governance is to improve the quality, efficiency, and effectiveness of the health system. The triple Burden of Disease (non-communicable diseases, infectious diseases, and external factors); fiscal and financial sustainability; and the need to improve the effectiveness and quality of medical care necessitate profound changes in the health system and make it critical to bring about its digital transformation

Efectos del aprendizaje colaborativo en el uso de estrategias de afrontamiento / Effects of collaborative learning on the use of coping strategies

El objetivo de este trabajo es demostrar que el uso de técnicas de aprendizaje colaborativo en el aula permite a los alumnos utilizar estrategias mediante las cuales aprenden a afrontar situaciones problemáticas derivadas de las relaciones interpersonales que se producen en el espacio educativo, especialmente entre iguales. Participaron 50 niños y niñas de primer curso de Educación Secundaria Obligatoria (edad media 12.4 años) distribuidos en dos grupos: experimental y control. En el primer grupo, se utilizó un programa basado en el aprendizaje individual asistido por un equipo; en el segundo, se utilizó una metodología de corte tradicional. Para probar las hipótesis formuladas, utilizamos un diseño de grupo de control pretest-postest con grupo de control no equivalente. Consideramos la inteligencia como covariable para mantener constantes sus efectos sobre los resultados independientemente del efecto del programa. Empleamos un análisis de varianza split-plot univariado como procedimiento estadístico. Los resultados muestran que los alumnos que siguen un programa de aprendizaje colaborativo utilizan más y mejores estrategias de afrontamiento que aquellos que no lo hacen. Los participantes de los grupos experimental y control parten de una situación de igualdad para separarse en la situación postest: el grupo experimental aumenta significativamente sus puntuaciones con respecto al grupo de control en lo que se refiere al uso de las estrategias de afrontamiento, y sus participantes tienden a compartir sus problemas con los demás en mayor medida que los miembros del grupo de control, todo ello independientemente del CI.

The purpose of this work is to show that the use of collaborative learning techniques in the classroom allows students to use strategies through which they learn to cope with problematic situations derived from the interpersonal relations that take place at school, especially among peers. The participants have been 50 boys and girls, in first year of compulsory secondary education (average age, 12.4) distributed into two groups: experimental and control. In the first group Team Assisted Individualization has been used. In the second group a traditional methodology has been adopted. A pretest-posttest control group design with non-equivalent control group has been used to test the hypotheses. Intelligence has been used as covariable to keep its effect on the results constant, independently of the effects of the program. A univariate split-plot analysis has been used as statistic procedure. The results show that those students on a collaborative learning program use more and more effective coping strategies than those who are not on a collaborative program. The participants in both the experimental and the control groups set out from a situation of equality to move farther away from each other in the posttest situation: the experimental group noticeably increases scores over the control group as regards the use of coping strategies, and the participants in the experimental group tend to share their problems with their peers in a greater scale than the participants in the control group, independently of the IQ.