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Mare endometrosis is a major reproductive problem associated with low fertility and is characterized by persistent inflammation, TGFβ-1 signaling, and consequently, extracellular matrix deposition, which compromises endometrial glands. Mesenchymal stem cell-based products (MSCs), such as extracellular vesicles (EVs), have gained attention due to the regulatory effects exerted by their miRNA cargo. Here, we evaluated the impact of preconditioning equine adipose mesenchymal stem cells with TGFβ-1 for short or long periods on the anti-fibrotic properties of secreted extracellular vesicles. MSCs were isolated from six healthy horses and exposed to TGFβ-1 for 4, 24, and 0 h. The expression of anti-fibrotic and pro-fibrotic miRNAs and mRNAs in treated cells and miRNAs in the cargo of secreted extracellular vesicles was measured. The resulting EVs were added for 48 h to endometrial stromal cells previously induced to a fibrotic status. The expression of anti-fibrotic and pro-fibrotic genes and miRNAs was evaluated in said cells using qPCR and next-generation sequencing. Preconditioning MSCs with TGFβ-1 for 4 h enriched the anti-fibrotic miRNAs (mir29c, mir145, and mir200) in cells and EVs. Conversely, preconditioning the cells for 24 h leads to a pro-fibrotic phenotype overexpressing mir192 and mir433. This finding might have implications for developing an EV-based protocol to treat endometrial fibrosis in mares.

The mechanisms controlling soil succession in floodplains remain much less studied than in uplands due to the complexity that flooddriven erosion and sedimentation bring into soil development processes. The amount of organic matter and C generally grows with soil ageing and is controlled by multiple and interacting allogenic and autogenic factors, but to what extent the production of organic matter by in situ vegetation contributes to soil formation in floodplains remains unknown. The objective of this work was to explore the importance of autochthonous organic matter versus allochthonous organic matter in organic C accumulation of floodplain forest soils along a vegetation succession and hydrogeomorphic connectivity gradient. Physicochemical analyses of sediment collected after one single flood event in a large Mediterranean floodplain (Middle Ebro, a 9th order regulated river reach in NE Spain) were used to estimate the proportion of organic C found in the topsoil (first 10 cm) samples of young (50 yr) floodplain forests that had an allochthonous (i.e., % of organic C deposited by floods) or autochthonous (i.e., % of organic C produced in situ by vegetation) source. Results of this exploratory study showed that the accumulation of autochthonous organic C in the floodplain topsoil only occurred in floodplain forests older than 50 year-old, but even then, it was more than six-fold less abundant than that with an allochthonous origin. Moreover, a linear mixed effect model showed that, although autochthonous organic C accumulation was mainly explained by the forest structure, a small proportion of it was also controlled by an allogenic factor, the groundwater table depth. Then, groundwater table depth variations could be partly controlling autochthonous organic matter production and decomposition in this Mediterranean floodplain. Although flow regulation and embankment has dramatically limited the hydrogeomorphic dynamics of the river, allogenic overbank sedimentation during flood events still controls floodplain soil succession and organic C accumulation in the floodplain.

En este ensayo se explora el efecto de los programas de reforma al ajuste estructural del Estado costarricense sobre todas las áreas del entorno social, en especial la seguridad ciudadana del país. Se destaca la relación entre la desigualdad socioeconómica y la exclusión social, con la idea de que estas son las responsables de la inseguridad y el aumento de la criminalidad, cuando en estas zonas han sido excluidas del desarrollo económico generado por estas reformas de ajuste. La falta de acceso a servicios básicos, tales como salud, educación y empleo, genera estrés financiero y preocupaciones económicas, lo que puede desencadenar conflictos familiares y comportamientos violentos. Además, se afirma que las decisiones políticas tomadas desde la década de 1980 para cambiar el modelo económico existente hasta ese momento, han contribuido con la construcción de una sociedad que acentuó las desigualdades existentes en el modelo anterior. También, se plantea que el germen de la violencia es fruto de la desregularización de los controles del Estado, lo cual favorece el crimen organizado y la violencia intrafamiliar; así, la criminalidad se convierte en un refugio para aquellos sectores excluidos y desfavorecidos. Finalmente, se identifica una correlación entre la desigualdad socioeconómica, la violencia intrafamiliar y los homicidios, destacando la compleja interacción de estos fenómenos en la sociedad costarricense.

The severity of adenovirus infection or the success of adenovirus-vectorized gene therapy largely depends on the efficiency of viral entry into cells. Various drugs can alter viral entry. This study evaluated the effects of dexamethasone, paracetamol, diclofenac, ibuprofen, and ketorolac on adenovirus entry into cells in vitro and in vivo. SiHa cell cultures pretreated with dexamethasone, paracetamol, diclofenac, ibuprofen, ketorolac, or no drug were exposed to the Ad-BGal vector. The percentage of cells showing vector entry was quantified microscopically. In vivo, BALB-C mice pretreated for 7 days with the drugs or no drug were exposed to the Ad-BGal vector intravenously (IV) or via oral (VO). Organs showing vector entry were identified by X-Gal staining and eosin counterstaining. Hepatic areas with adenovirus entry were quantified in µm2. Dexamethasone, paracetamol, and ibuprofen increased adenovirus entry both in vitro and in vivo. Diclofenac increased entry only in vitro. Ketorolac did not affect adenoviral entry. The liver exhibited the most significant changes, with dexamethasone, paracetamol, and ibuprofen increasing adenovirus entry the most. Oral administration of the vector showed that dexamethasone increased its entry into the pharynx. Some physicochemical properties of the drugs (MW (g/mol), LogP, MR [cm3/mol], tPSA, CMR, LogS, and ClogP) were analyzed, and their possible implications on cell membrane properties that could potentially influence adenovirus entry through mechanisms independent of cellular receptors were discussed. Anti-inflammatory drugs could alter adenoviral infections and adenovirus vector-based gene therapies, necessitating further research.

Abstract Brain development involves a sequence of structural changes from early stages of the embryo until several months after birth. Currently, ultrasound is the established technique for screening due to its ability to acquire dynamic images in real-time without radiation and to its cost-efficiency. However, identifying abnormalities remains challenging due to the difficulty in interpreting foetal brain images. In this work we present a set of 104 2D foetal brain ultrasound images acquired during the 20th week of gestation that have been co-registered to a common space from a rough skull segmentation. The images are provided both on the original space and template space centred on the ellipses of all the subjects. Furthermore, the images have been annotated to highlight landmark points from structures of interest to analyse brain development. Both the final atlas template with probabilistic maps and the original images can be used to develop new segmentation techniques, test registration approaches for foetal brain ultrasound, extend our work to longitudinal datasets and to detect anomalies in new images.

Abstract This paper offers a comprehensive analysis of Spain’s corporate tax system through the lens of the Laffer curve and Buoyancy index, assessing its efficiency in generating revenue. The study finds that Spain is nearing the Laffer curve’s optimal tax rate, beyond which tax revenue may decrease with rate hikes. The Buoyancy index reveals a fluctuating response of tax revenues to economic shifts, indicating vulnerability in economic downturns. We trace Spain’s corporate tax evolution, examining current structures and recent policy reforms, and explore how corporate taxation influences economic activities and investment. The paper proposes policy recommendations, including reassessing the corporate tax rate, advocating structural reforms for a wider tax base, and policies promoting economic growth. Emphasis is placed on counter-cyclical fiscal policies, regular evaluation of tax incentives, improving tax compliance, and Spain’s role in global tax coordination. This research contributes to fiscal policy discussions, advocating a balanced tax approach for sustainable economic development and guiding policymakers toward resilient fiscal strategies in a dynamic economic environment.

Abstract The purpose of this was to improve the procedure for making cheese in the Antonio dairy company applying Six Sigma. The following work was presented, which focused on reducing the variability of the weight of the units made. It begins with the DMAIC methodology in the definition phase of the problem with the data record of the productive part to apply tools such as the five whys, Ishikawa diagram, analysis of variances. The mixed experimental design of three factors is executed, taking into account the discharge speed of the curd, hardening time, and the operators who work in the process, where it is determined that 70.26% of the variability of the weight of the cheeses are caused by these three factors. In the part that corresponds to results in the improvement of the production process of the product detailed in this study, it is focused on these important points. Regarding the application of the improvement of the process, a 15 minutes increase is made in the hardening of the curd after having carried out the standardization in the unloading taking speed as a variable. In said improvement, all the personnel that work in the dosing machine, thus managing to reduce variability by 24.37% and likewise reduce the number of cuts and waste in the production line with a saving of 44,616 USD per year.

Abstract Background Systemic lupus erythematosus (SLE) may result in great impact on patients’ quality of life, social relationships, and work productivity. The use of patient-reported outcome measures (PROMs) in routine care could help capture disease burden to guide SLE management and optimize disease control. We aimed to explore the current situation, appropriateness, and feasibility of PROMs to monitor patients with SLE in routine care, from healthcare professionals’ and patients’ perspectives. Methods A scientific committee developed a Delphi questionnaire, based on a focus group with patients and a literature review, including 22 statements concerning: 1) Use of PROMs in routine care (n = 2); 2) PROMs in SLE management (n = 13); 3) Multidisciplinary management of patients with SLE (n = 4), and 4) Aspects on patient empowerment (n = 3). Statements included in Sects. 2–4 were assessed from three perspectives: current use, appropriateness, and feasibility (with currently available resources). For each statement, panellists specified their level of agreement using a 7-point Likert scale. A consensus was reached when ≥ 70% of the panellists agreed (6,7) or disagreed (1,2) on each statement. Results Fifty-nine healthcare professionals and 16 patients with SLE participated in the Delphi-rounds. A consensus was reached on the value of PROMs to improve SLE management (83%) and the key role of healthcare professionals (77%) and the need for a digital tool connected to the electronic medical record (85%) to promote and facilitate PROMs collection. PROMs most frequently used in clinical practice are pain (56%), patient’s global assessment (44%) and fatigue (39%), all on visual analogue scales. Panellists agreed on the need to implement multidisciplinary consultation (79%), unify complementary tests (88%), incorporate pharmacists into the healthcare team (70%), and develop home medication dispensing and informed telepharmacy programmes (72%) to improve quality of care in patients with SLE. According to panellists, patient associations (82%) and nurses (80%) are critical to educate and train patients on PROMs to enhance patient empowerment. Conclusions Although pain, fatigue, and global assessment were identified as the most feasible, PROMs are not widely used in routine care in Spain. The present Delphi consensus can provide a road map for their implementation being key for SLE management.

El turismo es un sector para considerar en el desarrollo de cualquier país, pues en todos los territorios existen recursos importantes, tanto económicos, humanos, institucionales como culturales, que pudieran ser utilizados racionalmente a favor del desarrollo turístico sostenible, partiendo de las diversas iniciativas locales que generan grandes oportunidades y formas de crecimiento económico. Es objetivo de este artículo valorar la oferta turística rural en Ecuador y su redimensionamiento durante el período pospandémico. Durante el proceso investigativo se aplicaron métodos y técnicas tales como análisis documental, análisis histórico-lógico y analítico-sintético. También el cálculo porcentual, tablas y gráficos. Como principales hallazgos se pueden citar: La demanda turística en el Ecuador, en estos momentos acentúa su interés a lo rural, y vivencial; la oferta turística rural debe ser auténtica y diversa, vinculando modernidad y tecnología; el turismo rural requiere la integración de todos los factores políticos, económicos y sociales, para alcanzar el éxito y generar beneficios comunes. En conclusión, este artículo corroboró que el turismo rural es un nicho de mercado de alto impacto para diversificar la economía ecuatoriana, restablecer los flujos turísticos, la preservación de las comunidades autóctonas y su cultura, toda vez, que se garantiza la protección de los ecosistemas existentes.

Abstract In the context of tissue engineering, biofabrication techniques are employed to process cells in hydrogel-based matrices, known as bioinks, into complex 3D structures. The aim is the production of functional tissue models or even entire organs. The regenerative production of biological tissues adheres to a multitude of criteria that ultimately determine the maturation of a functional tissue. These criteria are of biological nature, such as the biomimetic spatial positioning of different cell types within a physiologically and mechanically suitable matrix, which enables tissue maturation. Furthermore, the processing, a combination of technical procedures and biological materials, has proven highly challenging since cells are sensitive to stress, for example from shear and tensile forces, which may affect their vitality. On the other hand, high resolutions are pursued to create optimal conditions for subsequent tissue maturation. From an analytical perspective, it is prudent to first investigate the printing behavior of bioinks before undertaking complex biological tests. According to our findings, conventional shear rheological tests are insufficient to fully characterize the printing behavior of a bioink. For this reason, we have developed optical methods that, complementarily to the already developed tests, allow for quantification of printing quality and further viscoelastic modeling of bioinks.

Abstract Objectives Due to the increase in the prevalence of non-communicable diseases and the Colombian demographic transition, the necessity of palliative care has arisen. This study used accessibility and coverage indicators to measure the geographic barriers to palliative care. Methods Population-based observational study focused on urban areas and adult population from Colombia, which uses three measurements of geographic accessibility to services: a) density of palliative care services per 100,000 inhabitants, b) analysis of geographic distribution by territorial nodes of the country, and c) spatial analysis of palliative care services using Voronoi diagrams. ArcGIS Pro software was used to map services’ locations and identify geographic disparities. Results A total of 504 palliative care services were identified, of which 77% were primary health care services. The density of palliative care services in Colombia is 1.8 primary care services per 100,000 inhabitants and 0.4 specialized services per 100,000 inhabitants. The average palliative care coverage is 41%, two regions of the country have a coverage below 30%. Twenty-eight percent of the services provide care for a population greater than 50,000 inhabitants within their coverage area, exceeding the acceptable limit by international standards. Conclusions Palliative care services are concentrated in three main regions (Bogotá D.C., the Center, and the Caribbean) and are limited in the Orinoquia and Amazonia nodes. Density of specialized palliative care services is extremely low and there are regions without palliative services for adults with palliative needs.

Considering the recent epigenetic studies on the transgenerational transmission of trauma, this article aims to 1) explore its ethical implications for the concept and nature of moral damage, and 2) offer normative suggestions on collective responsibilities both synchronic and diachronic. To do so, I first address recent epigenetic studies’ showing the crystallization of emotional information through generations, and second, defend that a unified approach to the concept of ghost damage may be useful to categorize this phenomenon, facilitate future research on this type of moral damage, and recognize its importance in the identification of hermeneutical injustice. Finally, I suggest that granting a right to transgenerational information may help avoid the perpetuation of inherited damage that jeopardize mental and physical health in the offspring.

The Protein Phosphatase type 1 catalytic subunit (PP1c) (PF3D7_1414400) operates in combination with various regulatory proteins to specifically direct and control its phosphatase activity. However, there is little information about this phosphatase and its regulators in the human malaria parasite, Plasmodium falciparum. To address this knowledge gap, we conducted a comprehensive investigation into the structural and functional characteristics of a conserved Plasmodium-specific regulator called Gametocyte EXported Protein 15, GEXP15 (PF3D7_1031600). Through in silico analysis, we identified three significant regions of interest in GEXP15: an N-terminal region housing a PP1-interacting RVxF motif, a conserved domain whose function is unknown, and a GYF-like domain that potentially facilitates specific protein-protein interactions. To further elucidate the role of GEXP15, we conducted in vitro interaction studies that demonstrated a direct interaction between GEXP15 and PP1 via the RVxF-binding motif. This interaction was found to enhance the phosphatase activity of PP1. Additionally, utilizing a transgenic GEXP15-tagged line and live microscopy, we observed high expression of GEXP15 in late asexual stages of the parasite, with localization predominantly in the nucleus. Immunoprecipitation assays followed by mass spectrometry analyses revealed the interaction of GEXP15 with ribosomal- and RNA-binding proteins. Furthermore, through pull-down analyses of recombinant functional domains of His-tagged GEXP15, we confirmed its binding to the ribosomal complex via the GYF domain. Collectively, our study sheds light on the PfGEXP15-PP1-ribosome interaction, which plays a crucial role in protein translation. These findings suggest that PfGEXP15 could serve as a potential target for the development of malaria drugs.

Technology has become invaluable and digital competence has turned into a necessity for students. The research presented here aims to propose mediation models that explain the influence of attitudinal, technology use, and family factors on the level of digital problem-solving skills of compulsory education students (12-14 years old). A quantitative methodology with a cross-sectional design was used. We worked with a sample of 772 students from 18 Spanish educational centres according to a stratified random sampling method. For data collection, an objective assessment test was used for knowledge and skills, and a Likert scale for attitudes. Regression analyses were carried out by creating theoretical reference models based on the bootstrapping technique. The results showed that students who expressed a favourable attitude towards digital problem solving demonstrated a better level of competence, which was also positively influenced by the possession of technological devices and the frequency of their use for school and non-school activities at home.

The objective of this study was to promote the use of metaphorical stories based on classical Greek myths in academic teacher training. The aim is to favour processes of personal assemblage and the constitution of teacher identity. Based on 8 classical myths, 4 of them featuring a female character and another 4 a male character, the group of participants narrated positive as well as disappointing experiences they had lived through during their academic training. Moreover, they selected the myths, among those proposed, that provided the metaphors that best described their specific personal trajectories. Adopting a qualitative approach, we followed a narrative-biographical tradition and collected 37 stories. This narrative corpus was analysed using the AQUAD software. The results showed that classical Greek myths contain and provide a powerful and illuminating narrative scaffolding, helping students to adopt a different perspective in the narration of their own academic trajectories. The myths equally helped them to become more aware of the most genuine life and personal experiences that shaped their own teacher identity.