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Abstract Treatment based on immune checkpoint blockade has revolutionized cancer therapy. Despite the remarkable success achieved and the preclinical development of multiple checkpoint inhibitors targeting other checkpoints, only antibodies targeting the PD-1/PD-L1 axis and CTLA-4 have been approved for patient treatment, especially in solid tumors. Currently, with the approval of relatlimab, a LAG-3 blocking antibody, a third player, has been used in the fight against cancer. The endorsement of relatlimab marks a significant milestone in cancer immunotherapy, opening new avenues for combination therapies and enhancing treatment outcomes. However, the complex biology of LAG-3 may hinder its full development as a therapeutic alternative. In this review, we provide in-depth insight into the biology of LAG-3 and its current and future development in cancer treatment.

Abstract Background Access to essential diagnostics is crucial for primary healthcare (PHC) in low-and-middle income countries (LMICs). Many LMICs have invested in equipping PHC with point-of-care (PoC) diagnostics for infectious diseases, however there has been no similar investment to improve PHC capacities for clinical chemistry. The biochemistry gap is among the deterrents to universal health coverage. Methods A social sciences project was conducted with the aim to understand the key PHC stakeholders’ insights on the pertinence of PoC biochemistry for PHC in LMICs. Data generation was conducted between July-November 2023 in Mongolia, Nigeria and Peru. Decision-makers in healthcare delivery, healthcare professionals, and patient and community advocates were engaged using a combination of sampling techniques. Unstructured individual and group conversations, and non-participant observation were conducted. Analysis involved an inductive line-by-line coding on printed transcripts, followed by a deductive coding and theme-by-theme analysis on digitized transcripts. Results Fifteen, 51 and 20 informants from Mongolia, Nigeria and Peru, respectively, participated. Fifty-five of the 94 informants were female. Most informants considered that PoC biochemistry in PHC would be pertinent, from a clinical and a resources-saving perspective. Those households that currently bear the burden of referrals (i.e., the poor, the bedridden, the older adults) would benefit the most from the deployment of PoC biochemistry for essential biochemistry parameters. Improved access to PoC glycated hemoglobin (HbA1c), lipid, liver and kidney profile was perceived as helpful to inform clinicians’ decision-taking. The value of PoC biochemistry for the management of noncommunicable diseases (diabetes, hypertension) and infectious conditions (dengue, malaria, tuberculosis), to improve child health outcomes (severe dehydration in children with diarrhea and/or malnutrition) and to reduce preventable causes of death (dengue-related renal failure) was highlighted. Conclusions PoC biochemistry holds potential to revert the impact that the biochemistry gap has for patient care in some LMICs’ PHC settings. PoC equipment for parameters such as HbA1c, urea, creatinine or electrolytes could enhance community-level management of preventable causes of mortality, improve service delivery for patients affected by locally-prevalent infectious conditions, and improve the psychosocial and economic wellbeing of patients facing the burden of referrals to remote biochemistry-equipped centers. Trial Registration Not applicable.

Rosario Tourino-Peralba,1,2,* David Lamas-Francis,1,* Laura Freijeiro-Gonzalez,3 Laura Martínez-Pérez,1 Teresa Rodríguez-Ares1 1Department of Ophthalmology, University Hospital of Santiago de Compostela, Santiago, Spain; 2Department of Surgery and Medical-Surgical Specialities, Faculty of Medicine, University of Santiago de Compostela, Santiago, Spain; 3Department of Statistics, Faculty of Mathematics, University of Santiago de Compostela, Santiago, Spain*These authors contributed equally to this workCorrespondence: Rosario Tourino-Peralba, Department of Ophthalmology, University Hospital of Santiago de Compostela, Ramón Baltar s/n, 15706, Santiago de Compostela, Spain, Tel +34 981 951 749, Email rtourinop2@gmail.com; david.lamas@outlook.esPurpose: This study aims to analyze the incidence of pseudophakic macular edema (PME) and the role of contributing risk factors following prepupillary or retropupillary implantation of iris-claw lenses.Methods: This retrospective cohort study included patients who underwent iris-claw intraocular lens implantation over a 16-year period at the University Hospital of Santiago de Compostela, Spain. The presence of risk factors for PME was recorded, and surgical outcomes included visual acuity, macular OCT scans, and description of complications.Results: A total of 148 eyes from 147 patients were included. Seventy-nine eyes (54.4%) underwent prepupillary iris-claw lens implantation and 69 eyes (46.6%) underwent retropupillary implantation. The mean age of the patients was 68.9 ± 17.2 years. The incidence of PME post-surgery was 23.0% (26.6% prepupillary and 18.8% retropupillary), and the mean time between surgery and diagnosis was similar for both locations (4.8 and 4.7 months, respectively). PME recurred in 33% of the patients, reaching a high rate of 72.7% when the lens location was prepupillary. The mean best-corrected visual acuity was 0.66± 0.55 logMAR preoperatively and 0.38± 0.50 logMAR postoperatively. Postoperative complications occurred in 29 patients (19.6%).Conclusion: PME following iris-claw lens implantation tends to be more frequent and recurrent when the location is prepupillary. Planning for iris-claw lens surgery should consider the risk factors for the development of PME.Keywords: macular edema, aphakia, pseudophakia, iris-anchored intraocular lenses

La animación se ha hecho eco de la importancia que la salud mental ha adquirido recientemente en la sociedad. Identificar las emociones propias e interpretarlas para saber cómo desarrollar habilidades, tomar decisiones y, en definitiva, conocerse individualmente, suponen uno de los principales retos a los que se enfrenta el sujeto contemporáneo. Este artículo explora, desde una perspectiva de género, el tratamiento de la inteligencia emocional en la ficción surcoreana a través de la serie Yumi’s Cells (2021-2022), que combina imagen real y animación. Mediante un análisis textual, se confirma que la representación de los personajes animados sirve como una herramienta pedagógica para que la audiencia aprenda a detectar las emociones cotidianas, particularmente en un contexto como el de la sociedad surcoreana que adolece de determinados recursos psicológicos, pues la extroversión de las emociones es considerada un tabú social.

Introduction and aim: Adherence to colorectal cancer (CRC) screening is essential for the effectiveness of screening programs. Even though organized screening programs can improve the quality of the process and adherence, there are still challenges to overcome. The aim of the present study, in which we implemented a biennial organized screening program for CRC, was to describe adherence and participation patterns. Materials and methods: A longitudinal, descriptive study was conducted, in which a team of trained patient navigators carried out interventions, with reminders via cellphone communication, to follow a cohort of 301 subjects eligible for CRC screening, utilizing a fecal immunochemical test (FIT). All the follow-up subjects received a FIT kit. Results: A total of 747 cellphone calls were made and divided into three interventions. From the initial cohort, 126 subjects completed their biennial screening process through the FIT, indicating a consistent adherence rate of 41.8% to our program. The participation patterns were: 126 consistent participants (41.8%), 160 inconsistent participants (53.2%), and 15 participants that were never contacted (5%). Conclusions: In conclusion, our study underlines the importance of organized screening programs in the early detection of CRC. The implementation of follow-up interventions, through reminders and the training of patient navigators, can improve adherence, but there is a need for examining new strategies, to overcome barriers to communication via cellphone. Resumen: Introducción y objetivo: La adherencia al tamizaje del cáncer colorrectal (CCR) es esencial para la efectividad de los programas de escrutinio. A pesar de que los programas de tamizaje organizado pueden mejorar la calidad del proceso y la adherencia, aún hay desafíos para lograrlo. En este estudio, implementamos un programa bienal de tamizaje organizado para CCR con el objetivo de describir la adherencia y los patrones de participación. Materiales y métodos: Se realizó un estudio longitudinal y descriptivo en el que un equipo de navegadores de pacientes capacitados realizó intervenciones con recordatorios mediante llamadas telefónicas para dar seguimiento a una cohorte de 301 sujetos elegibles para el tamizaje de CCR mediante una prueba de inmunoquímica fecal (FIT). Todos los participantes que cumplieron con su seguimiento recibieron un Kit FIT. Resultados: Se realizaron 747 llamadas telefónicas divididas en tres intervenciones. De la cohorte inicial, 126 sujetos completaron su proceso de tamizaje bienal mediante FIT, lo que indica una adherencia consistente del 41.8% a nuestro programa. Los patrones de participación fueron 126 participantes consistentes (41.8%), 160 inconsistentes (53.2%) y 15 nunca atendidos (5%). Conclusiones: En conclusión, nuestro estudio resalta la importancia de los programas de tamizaje organizado en la detección temprana del cáncer colorrectal. La implementación de intervenciones de seguimiento mediante recordatorios y la capacitación de navegadores de pacientes, puede lograr mejoras en la adherencia, sin embargo, es necesario explorar nuevas estrategias para superar las barreras en la comunicación telefónica.

Resumen: Introducción y objetivo: La adherencia al tamizaje del cáncer colorrectal (CCR) es esencial para la efectividad de los programas de escrutinio. A pesar de que los programas de tamizaje organizado pueden mejorar la calidad del proceso y la adherencia, aún hay desafíos para lograrlo. En este estudio implementamos un programa bienal de tamizaje organizado para CCR con el objetivo de describir la adherencia y los patrones de participación. Materiales y métodos: Se realizó un estudio longitudinal y descriptivo en el que un equipo de navegadores de pacientes capacitados realizó intervenciones con recordatorios mediante llamadas telefónicas para dar seguimiento a una cohorte de 301 sujetos elegibles para el tamizaje de CCR mediante una prueba de inmunoquímica fecal (FIT). Todos los participantes que cumplieron con su seguimiento recibieron un kit FIT. Resultados: Se realizaron 747 llamadas telefónicas divididas en tres intervenciones. De la cohorte inicial, 126 sujetos completaron su proceso de tamizaje bienal mediante FIT, lo que indica una adherencia consistente del 41.8% a nuestro programa. Los patrones de participación fueron 126 participantes consistentes (41.8%), 160 inconsistentes (53.2%) y 15 nunca atendidos (5%). Conclusiones: Nuestro estudio resalta la importancia de los programas de tamizaje organizado en la detección temprana del cáncer colorrectal. La implementación de intervenciones de seguimiento mediante recordatorios y la capacitación de navegadores de pacientes, puede lograr mejoras en la adherencia; sin embargo, es necesario explorar nuevas estrategias para superar las barreras en la comunicación telefónica. Abstract: Introduction and aim: Adherence to colorectal cancer (CRC) screening is essential for the effectiveness of screening programs. Even though organized screening programs can improve the quality of the process and adherence, there are still challenges to overcome. The aim of the present study, in which we implemented a biennial organized screening program for CRC, was to describe adherence and participation patterns. Materials and methods: A longitudinal, descriptive study was conducted, in which a team of trained patient navigators carried out interventions, with reminders via cellphone communication, to follow a cohort of 301 subjects eligible for CRC screening, utilizing a fecal immunochemical test (FIT). All the follow-up subjects received a FIT kit. Results: A total of 747 cellphone calls were made and divided into three interventions. From the initial cohort, 126 subjects completed their biennial screening process through the FIT, indicating a consistent adherence rate of 41.8% to our program. The participation patterns were: 126 consistent participants (41.8%), 160 inconsistent participants (53.2%), and 15 participants that were never contacted (5%). Conclusions: In conclusion, our study underlines the importance of organized screening programs in the early detection of CRC. The implementation of follow-up interventions, through reminders and the training of patient navigators, can improve adherence, but there is a need for examining new strategies, to overcome barriers to communication via cellphone.

Introduction ISMiHealth is a clinical decision support system, integrated as a software tool in the electronic health record system of primary care, that aims to improve the screening performance on infectious diseases and female genital mutilation (FGM) in migrants. The aim of this study is to assess the health impact of the tool and to perform a process evaluation of its feasibility and acceptability when implemented in primary care in Catalonia (Spain).Methods and analysis This study is a cluster randomised control trial where 35 primary care centres in Catalonia, Spain will be allocated into one of the two groups: intervention and control. The health professionals in the intervention centres will receive prompts, through the ISMiHealth software, with screening recommendations for infectious diseases and FGM targeting the migrant population based on an individualised risk assessment. Health professionals of the control centres will follow the current routine practice.A difference in differences analysis of the diagnostic rates for all aggregated infections and each individual condition between the intervention and control centres will be performed. Mixed-effects logistic regression models will be carried out to identify associations between the screening coverage and predictor factors. In addition, a process evaluation will be carried out using mixed methodology.Ethics and dissemination The study protocol has been approved by the institutional review boards at Hospital Clínic (16 June 2022, HCB/2022/0363), Clinical Research Ethics Committee of the Primary Care Research Institute IDIAPJGol (22 June 2022, 22/113-P) and the Almería Research Ethics Committee (27 July 2022, EMC/apg). The study will follow the tenets of the Declaration of Helsinki and Good Clinical Practice. All researchers and associates signed a collaboration agreement in which they undertake to abide by good clinical practice standards.Findings will be disseminated in peer-reviewed journals and communications to congresses.Trial registration number NCT05868005.

ABSTRACT The impact of third-generation cephalosporin-resistant Enterobacterales (3GCR-E) rectal colonization in the development of subsequent infection after surgery is controversial. In particular, there is a lack of data in the context of hepato-pancreato-biliary (HPB) surgery. The objective of this study was to assess the prevalence of 3GCR-E intestinal carriage among patients undergoing elective HPB resection surgery and its impact on the incidence and etiology of surgical site infections (SSIs). This retrospective cohort study (January 2016–December 2022) was performed at Valme University Hospital (Seville, Spain). The inclusion criteria included (i) 18 years of age or older, (ii) undergoing elective HPB resection surgery, and (iii) availability of a periprocedural surveillance rectal swab culture to detect 3GCR-E. The prevalence of 3GCR-E intestinal carriage at elective HPB resection surgery was assessed, as well as SSI incidence at 30 days and possible associated factors. Two hundred nine patients were included. Eleven (5.3%) patients were colonized by 3GCR-E at baseline. According to 3GCR-E carriage status, 6 (55%) of the carriers developed SSI, whereas this occurred in 50 (25%) of non-carriers (P = 0.033). Likewise, the rates of SSI caused specifically by 3GCR-E were 83% (5 of 6) in 3GCR-E carriers and 6% (3 of 50) in non-carriers (P < 0.001). After multivariate analyses, 3GCR-E colonization at the time of surgery was identified as an independent predictor for developing SSI (adjusted odds ratio 4.63, 95% confidence interval: 1.177–18.232, P = 0.028). Despite a low prevalence of 3GCR-E intestinal carriage at surgery, 3GCR-E rectal colonization is associated with a higher risk of SSI among patients undergoing elective HPB resection surgery, with most SSIs being caused by the colonizing bacteria.IMPORTANCEIn this Spanish retrospective cohort study, previous 3GCR-E rectal colonization was associated with a higher risk of SSI after hepato-pancreato-biliary resection surgeries. Most of SSIs were caused by the colonizing bacteria, suggesting a rationale for adapted perioperative antibiotic prophylaxis in known 3GCR-E colonized patients.

The acceptance of strawberries in international trade has increased due to their organoleptic qualities, high nutritional value, and richness in antioxidants. This research evaluated the effect of foliar spray with chitosan, brassinosteroids, and thidiazuron as metabolic enhancers on growth, productivity, quality parameters, and bioactive compounds in ‘Portola’ strawberry cultivar in the first year of production. This experiment included six treatments and control with doses of CTS of 100, 300, and 400 mg L-1, of Brassinosteroids (Vitazyme™) 0.5, 1-, and 5-mL L-1 and 0.15 mL L-1 of TDZ (Charger plex™) in applications of these biostimulants alone and combination CTS and BRs. The findings indicated that CTS treatments increased plant length, leaf count, leaf area, and fruit firmness. The joint application of CTS and BRs significantly promotes crown diameter, photosynthetic pigments, carotenoids, fresh and dry weight of roots and aerial parts, and ripening. Applications of CTS 300 mg L-1 and 1 mL L-1 of Vitazyme have shown the highest fruit length, diameter, and weight values. Regarding TDZ, this work showed an increase in crown diameter and in the fresh and dry weight of both the root and the aerial part without significant differences in the content of the chlorophyll and titratable acidity compared to the control. Therefore, it could be safely recommended that foliar application with CTS, BRs, and TDZ can be used as biostimulants to improve the growth, quality and bioactive compounds of strawberry cv ‘Portola’.

Se describe un reporte de caso de un paciente masculino de 61 años que acude a emergencia por presentar cuadro clínico de una semana de evolución caracterizada por disnea de mínimos esfuerzos, disfonía, dolor precordial, y fatiga, acompañado de pérdida de peso. En la analítica de laboratorio destaca: anemia normocítica normocrómica, leucocitosis con neutrofilia, trombocitosis, creatinina de 10.1mg/dL, PCR elevada, proteinuria con hematuria y Anti-PR3-ANCA positivo. Biopsia renal revela glomerulonefritis proliferativa extracapilar pauci-inmune (“crescéntica”), etiquetando el diagnóstico como vasculitis asociada a ANCA con glomerulonefritis rápidamente progresiva. Se maneja inducción y mantenimiento con rituximab y esteroides en pulsos.

La arteritis de Takayasu (TAK) es una vasculitis crónica, poco frecuente, de grandes vasos que afecta a la aorta y sus grandes ramas. El daño valvular no es bajo, aunque su incidencia difiere entre poblaciones, con un reporte entre el 20 a 45% con un radio mujer:hombre de 4.8 a 1.La inflamación arterial es la característica central de la enfermedad, asociada de forma variable con una respuesta sistémica de fase aguda. Se presenta el caso de una mujer de 25 años con antecedentes de atrofia renal e insuficiencia cardiaca que presentó convulsiones, se identifica discrepancia en presión arterial y pulsos periféricos de extremidades; corroborándose sospecha diagnóstica.

The time-consuming nature of many sample treatment protocols continues to be recognized as the main bottleneck of analytical procedures, which, in most cases, use long analysis times, excessive amounts of solvents and reagents, and energy. However, the increased awareness of the need for environmental protection and the development of Green Analytical Chemistry (GAC) has led to significant advancements in the field of sample treatment. Today, advances in the miniaturization of sample treatment techniques, the development of sorbents with tunable properties, and greener alternatives (for example from waste valorization) are gaining interest in the analysis of psychoactive compounds. Indeed, techniques offering rapid sample preparation, minimal use of solvents, reagents, and energy, and a significant reduction of waste generation are chosen by the scientific community. In recent years, non-toxic extraction media, such as ionic liquids, and deep eutectic solvents have emerged as alternatives to petroleum-based solvent extractions. Similarly, sorbent-based techniques have benefited from engineered materials and nanotechnology, incorporating novel sorbents with optimized physicochemical properties to enhance extraction efficiency and selectivity. To meet sustainability standards, GAC provides a wealth of information in the field of green awareness, and the application of green metrics has been extended into the literature in the past decade. These tools serve as guides and encourage scientists to develop the most appropriate methodologies that focus on both analytical performance and sustainability, using different concepts and criteria. This article collects and discusses examples of different sample preparation techniques applied to drug analysis, highlighting their strategies for greening the processes and their evaluation using tools such as HEXAGON, Analytical greenness metric for sample preparation (AGREEprep), and Sample preparation metric of sustainability (SPMS) tools.

Hydrological models can benefit from soft calibration, a process by which the proper simulation of hydrological variables is proved while or before addressing hard calibration. Soft calibration reduces the probability of obtaining a statistically accurate but unrealistic model. However, it requires soft data, which is often hard to acquire or unavailable. This work presents HydRoVars, an R tool developed to facilitate the estimation of data which can be implemented in a soft calibration procedure. It allows us to estimate two key hydrological indices (the runoff coefficient and baseflow index) and weather-related variables at the catchment scale for one or numerous basins. The runoff coefficient is calculated automatically from precipitation and streamflow datasets. Groundwater contribution is estimated through a semi-automatic process based on a baseflow filter which considers hydrogeological properties. Modellers would benefit from incorporating soft calibration in their calibration procedures, and this tool might help to estimate these relevant hydrological variables in their modelled area. The tool has been tested in 19 subbasins of the Tagus River basin (Spain) located in different geological regions. In the test cases, we demonstrate the usefulness of this tool to improve the model representation and gain an understanding of the catchments' hydrology. HIGHLIGHTS An R tool has been developed to collect weather and hydrological variables.; It allows estimating the runoff coefficient, and the baseflow index at the catchment scale.; Runoff coefficient can be automatically obtained for multiple basins.; Guidance is provided for a realistic groundwater contribution estimation.; Its usefulness has been tested in the Upper Tagus River basin (Spain).;

Abstract Background Due to population aging, healthcare expenditure is projected to increase substantially in developed countries like Spain. However, prior research indicates that health status, not merely age, is a key driver of healthcare costs. This study analyzed data from over 1.25 million residents of Spain's Murcia region to develop a capitation-based healthcare financing model incorporating health status via Adjusted Morbidity Groups (AMGs). The goal was to simulate an equitable area-based healthcare budget allocation reflecting population needs. Methods Using 2017 data on residents' age, sex, AMG designation, and individual healthcare costs, generalized linear models were built to predict healthcare expenditure based on health status indicators. Multiple link functions and distribution families were tested, with model selection guided by information criteria, residual analysis, and goodness-of-fit statistics. The selected model was used to estimate adjusted populations and simulate capitated budgets for the 9 healthcare districts in Murcia. Results The gamma distribution with logarithmic link function provided the best model fit. Comparisons of predicted and actual average costs revealed underfunded and overfunded areas within Murcia. If implemented, the capitation model would decrease funding for most districts (up to 15.5%) while increasing it for two high-need areas, emphasizing allocation based on health status and standardized utilization rather than historical spending alone. Conclusions AMG-based capitated budgeting could improve equity in healthcare financing across regions in Spain. By explicitly incorporating multimorbidity burden into allocation formulas, resources can be reallocated towards areas with poorer overall population health. Further policy analysis and adjustment is needed before full-scale implementation of such need-based global budgets.

Abstract Background Klebsiella aerogenes has been reclassified from Enterobacter to Klebsiella genus due to its phenotypic and genotypic similarities with Klebsiella pneumoniae. It is unclear if clinical outcomes are also more similar. This study aims to assess clinical outcomes of bloodstreams infections (BSI) caused by K. aerogenes, K. pneumoniae and Enterobacter cloacae, through secondary data analysis, nested in PRO-BAC cohort study. Methods Hospitalized patients between October 2016 and March 2017 with monomicrobial BSI due to K. aerogenes, K. pneumoniae or E. cloacae were included. Primary outcome was a composite clinical outcome including all-cause mortality or recurrence until 30 days follow-up. Secondary outcomes were fever ≥ 72 h, persistent bacteraemia, and secondary device infection. Multilevel mixed-effect Poisson regression was used to estimate the association between microorganisms and outcome. Results Overall, 29 K. aerogenes, 77 E. cloacae and 337 K. pneumoniae BSI episodes were included. Mortality or recurrence was less frequent in K. aerogenes (6.9%) than in E. cloacae (20.8%) or K. pneumoniae (19.0%), but statistical difference was not observed (rate ratio (RR) 0.35, 95% CI 0.08 to 1.55; RR 0.42, 95% CI 0.10 to 1.71, respectively). Fever ≥ 72 h and device infection were more common in K. aerogenes group. In the multivariate analysis, adjusted for confounders (age, sex, BSI source, hospital ward, Charlson score and active antibiotic therapy), the estimates and direction of effect were similar to crude results. Conclusions Results suggest that BSI caused by K. aerogenes may have a better prognosis than E. cloacae or K. pneumoniae BSI.

Abstract Background Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann’s procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P

Abstract Polylactic acid (PLA) is a bioresorbable and biodegradable polymer extensively used in various biomedical and engineering applications. In this study, we investigated the mass loss and thermal properties of PLA-multi-walled carbon nanotube (MWCNT) composites under simulated physiological conditions. The composites were prepared by melting PLA with 0.1, 0.5, 1.0, and 5.0 wt% MWCNTs using an ultrasonic agitator, and FTIR analysis confirmed composite formation. Subsequently, the composites were subjected to hydrolysis under simulated physiological conditions (pH 7.4 and 37 °C) for up to 60 days. The results revealed that the mass loss of the composites decreased with increasing MWCNT content, suggesting that the presence of MWCNTs decelerated the hydrolysis process. On day 58, the mass loss of pure PLA was 12.5%, decreasing to 8.34% with 0.1% MWCNT, 5.94% with 0.5% MWCNT, 4.59% with 1% MWCNT, and 3.54% with 5.0% MWCNT. This study offers valuable insights into the behavior of PLA-MWCNT composites under physiologically simulated conditions, facilitating the development of new polymer composites with enhanced thermal stability and degradation resistance for biomedical applications.

Objectives: The early initiation of the empirical antibiotic treatment and its impact on mortality in patients with bacteraemia has been extensively studied. However, information on the impact of precocity of the targeted antibiotic treatment is scarce. We aimed to study the impact of further delay in active antibiotic therapy on 30-day mortality among patients with bloodstream infection who had not received appropriate empirical therapy. Design: We worked with PROBAC cohort (prospective and compound by patients from 26 different Spanish hospitals). We selected a total of 1703 patients, who survived to day 2 without having received any active antibiotic therapy against the causative pathogen. Results: The 30-day mortality was 14% (238 patients). The adjusted odds of mortality increased for every day of delay, from 1.53 (95% confidence interval (CI) 1.13-2.08) for day 3 or after to 11.38 (95% CI 7.95-16.38) for day 6 or after. Conclusion: We concluded that among patients who had not received active treatment within the first 2 days of blood culture collection, additional delays in active targeted therapy were associated with increased mortality. These results emphasize the importance of active interventions in the management of patients with bloodstream infections.

Fundamento: la aplicación de estrategias didácticas con enfoque de enseñanza productiva favorece el aprendizaje significativo en los estudiantes. Objetivo: determinar la efectividad de una estrategia didáctica para el proceso enseñanza aprendizaje del tema Fisiología del Sistema Respiratorio en estudiantes de la Filial de Ciencias Médicas de Puerto Padre durante el curso 2022. Métodos: se realizó una investigación cuasiexperimental con grupo control no equivalente y enfoque cuanticualitativo. Se utilizaron métodos teóricos: análisis-síntesis, inductivo-deductivo e histórico-lógico; empírico: cuestionario y análisis documental de los registros de promoción y asistencia. La promoción/calidad en las diferentes evaluaciones, la preferencia por el sistema respiratorio y el grado de satisfacción por la estrategia constituyeron las variables estudiadas. Se emplearon además métodos matemático-estadísticos para el análisis de los datos encontrados. Resultados: después de aplicada la estrategia, se alcanzó promoción satisfactoria en el seminario (91,8 %), prueba intrasemestral (94,5 %) y examen final (97,3 %) en la Fisiología del Sistema Respiratorio; el transporte de gases fue la función que exhibió los mejores resultados docentes con 98,6 % y 90,4 % (promoción/calidad); el 31,5 % de los estudiantes prefirieron el sistema respiratorio; el grado de satisfacción fue alto. Conclusiones: se determinó la efectividad de la estrategia didáctica del proceso enseñanza aprendizaje de Fisiología del Sistema Respiratorio implementada en estudiantes de Medicina de Puerto Padre.

El impacto social se define como el conjunto de cambios positivos en la vida de las personas asociados a problemas sociales, que son el efecto real de las intervenciones llevadas a cabo por la empresa. A pesar de la dificultad en su medición, las empresas híbridas lo consideran como un aspecto fundamental en la búsqueda por generar beneficios tanto sociales como económicos. La presente investigación tiene como objetivo realizar una revisión académica y clasificación de métodos cuantitativos relevantes para medir el impacto social generado por las empresas híbridas hacia su entorno. Se llevó a cabo a través de una revisión sistemática de la literatura en las bases de datos Scopus y Web of Science, complementada con un análisis de contenido web pertinente. Como resultado, se identificaron y clasificaron los 18 métodos más significativos de la actualidad. Se concluye que el impacto social es construido cognitivamente por cada actor individual, y a través de una negociación entre las partes interesadas, se llega a un acuerdo del significado dentro de su entorno. Por tanto, cada empresa puede conceptualizar la medición del impacto social de manera única, reflejando las particularidades y objetivos específicos de su actividad.

Resumen: Los tamales tsotsiles desempeñan un papel fundamental no sólo en la vida cotidiana, sino también en el contexto ritual. En el presente estudio se examinará cuál es el nombre genérico de tamal en esta lengua, cuántos tipos de tamales existen, en qué contextos se usan y cuáles son sus funciones. Veremos los diferentes tipos de envoltura que se usan para determinados tipos de tamales, señalaremos la relevancia de cada tipo de tamal y la razón de ello y finalmente se describirán las características del campo semántico y clase léxica. El presente estudio se sustenta desde el marco de la lingüística antropológica y la lexicología. La metodología usada para la recopilación de datos fue de corte etnográfico y lingüístico. La base de datos consta de 10 horas de videograbaciones sobre la elaboración de los tamales y de entrevistas semiestructuradas con las familias tsotsiles colaboradoras pertenecientes a los municipios de Huixtán, Zinacantán y Chamula, en Chiapas, México. Abstract: Tsotsil tamales play a fundamental role not only in daily life, but also in ritual context. In the present study, we will examine the generic name of tamale in the original language, how many types of tamales exist, in what contexts they are used and what are their functions. We will see the different types of wrapping used for certain types of tamales, we will point out the relevance of each type of tamale and the reason for them, and finally the characteristics of the semantic field and lexical class will be described. The present study is based on the framework of anthropological linguistics and lexicology. The methodology used for data collection was ethnographic. The database consists of ten hours of video recordings of the preparation of tamales and semi-structured interviews with collaborating Tsotsil families from the municipalities of Huixtán, Zinacantán and Chamula, in Chiapas, Mexico. This article is written in Spanish.

Abstract Background Rapid antigen-detection tests for SARS-CoV-2 self-testing represent a useful tool for pandemic control and expanding access to community-level case screening. COVID-19 self-tests have been extensively used in high-income countries since 2021; however, their introduction and programmatic implementation in low- and middle-income countries was delayed. We aimed to identify and continuously improve a weekly COVID-19 self-testing model among staff at healthcare facilities and schools. Methods This mixed-methods, observational prospective study was conducted in 5 healthcare centres and 24 schools in Georgia, between June and December 2022. The study comprised the integration of COVID-19 self-testing into the national mandatory testing programme for high-risk groups, with primary distribution of self-tests among staff performed weekly, plus secondary distribution to their household members. These use cases were selected because NCDC was seeking to strengthen their already strong weekly testing programme, by investigating self-testing to ease the burden of testing in the healthcare system. Online surveys and semi-structured interviews were used for data collection. Results In total, 2156 participants were enrolled (1963 female, 72%). At baseline and mid- and end-points, 88%, 97% and 99%, respectively, of participants agreed/strongly agreed they would self-test. Similarly, the majority were willing to report their self-testing results (88%, 98% and 96% at baseline and mid- and end-points, respectively). Weekly reporting of test results to the national COVID-19 database was high during all the implementation. There were 622 COVID-19 positive results reported, and linked to care, from 601 individuals (282 participants and 319 household members). Findings from qualitative interviews showed great satisfaction with self-testing for its convenience, ease of use, trust in the results, no need to travel for diagnostics, and increased perception of safety. Conclusions Our findings contribute to the evidence-base regarding self-testing strategies conducted via workplaces and secondary distribution to households. Willingness to perform a COVID-19 self-test increased after implementation. This pilot enhanced pandemic preparedness through expansion of the national self-testing reporting system, development of communications materials, changes in the national legal framework and coordination mechanisms, and improved perceptions around self-care in the community. The lessons learnt can inform operational aspects of the introduction and scale-up of self-care strategies.

Introducción: La divulgación de los resultados científicos son parte sustancial de los resultados en los procesos (I+D+i), son una vía de intercambio para los académicos de todo el mundo, además contribuyen a incrementar la visibilidad de las instituciones y el país. Objetivo: sistematizar las principales tendencias de publicación en el quehacer científico en Ecuador. Método: se empleó la metodología cualitativa con métodos teóricos de análisis, síntesis, inducción y deducción con la técnica de revisión documental. Resultados: se precisaron las características de la comunicación de la ciencia en Ecuador que se corresponden a las tendencias internacionales. Conclusión: se pudo constatar la evolución de las publicaciones en el país, tomando como referencia importantes bases de datos como Scopus, lo cual permite ubicar en el ranking actual determinadas investigaciones.

El fenómeno del maltrato entre iguales o bullying, lejos de disminuir, cada vez tiene un mayor impacto y repercusión social, menoscabando tanto a los escolares que lo padecen, como a los agresores y observadores inmersos en dicha problemática, y en conjunto, a toda la comunidad educativa: profesores, familias y alumnos. Catalogarlo como un reflejo de lo que sucede en la sociedad, ha ocasionado que esta problemática haya ido adquiriendo un mayor interés en los últimos años. Lo que se ha concretado, en el desarrollo por todo el territorio español, de programas e iniciativas de prevención de la violencia priorizando la convivencia. En este artículo, se analizan los principales programas de prevención del bullying elaborados en España en dos décadas (1997-2017), a través de una revisión sobre su estructura discursiva, estudiando sus similitudes o discrepancias. Los primeros resultados apuntan, entre otras cuestiones, la necesidad de que los programas aborden con mayor profundidad las interacciones de todos los agentes de la comunidad educativa (profesorado, alumnado, familia y comunidad) frente al bullying, contribuyendo a transmitir un posicionamiento unitario de todo el sistema educativo contra esta forma de violencia.

Sustainable water management should consider climate change effects to ensure its future availability. Hydrological modeling is a supportive tool for this analysis, which has been used in this work to assess the climate change impacts on the water resources of three basins under Mediterranean climate (Ompólveda and Salado River basins, in Spain, and Guadalupe River basin, in Mexico).The outcomes of previous climate change scenarios simulation addressed with the Soil and Water Assessment Tool (SWAT) have been compiled, evaluating the impacts on the water balance, and focusing on the streamflow components. The potential implications of these effects on energy production have been discussed.The results point to a streamflow reduction by the end of the century around 50%–60% in the worst scenarios, with varying effects for each of the streamflow components. In the Spanish catchments, where groundwater contribution dominates in baseline conditions, a noticeable decrease of this component is expected (up to -74%), becoming lateral flow the main streamflow component. In the Mexican basin, lateral flow, which is already predominant (69%), will experience the largest absolute decrease, but the highest relative decrease might be experienced by groundwater flow, up to -92%. Absolute variations in the surface component are small and the different ways to simulate the climate change scenarios might hinder their interpretation.This work shows that water resources will be even more scarce in these regions, being especially worrying the groundwater component reduction, which currently maintains the streamflow during dry periods. This situation would limit energy production both from sources that directly use water, such as hydropower, and others that require water for cooling. Higher atmospheric and water temperatures will increase demands for irrigation and for cooling systems. Therefore, competition for water will rise among key sectors, and an accurate planning considering these factors must be a priority.

T-cell acute lymphoblastic leukemia (T-ALL) is a challenging childhood cancer to treat, with limited therapeutic options and high relapse rates. This study explores deamidated triosephosphate isomerase (dTPI) as a novel therapeutic target. We hypothesized that selectively inhibiting dTPI could reduce T-ALL cell viability without affecting normal T lymphocytes. Computational modeling and recombinant enzyme assays revealed that disulfiram (DS) and curcumin (CU) selectively bind and inhibit dTPI activity without affecting the non-deamidated enzyme. At the cellular level, treatment with DS and CU significantly reduced Jurkat T-ALL cell viability and endogenous TPI enzymatic activity, with no effect on normal T lymphocytes, whereas the combination of sodium dichloroacetate (DCA) with DS or CU showed synergistic effects. Furthermore, we demonstrated that dTPI was present and accumulated only in Jurkat cells, confirming our hypothesis. Finally, flow cytometry confirmed apoptosis in Jurkat cells after treatment with DS and CU or their combination with DCA. These findings strongly suggest that targeting dTPI represents a promising and selective target for T-ALL therapy.

This paper presents an analysis and optimization of a polygeneration power-production system that integrates a concentrating solar tower, a supercritical CO2 Brayton cycle, a double-flash geothermal Rankine cycle, and an internal combustion engine. The concentrating solar tower is analyzed under the weather conditions of the Mexicali Valley, Mexico, optimizing the incident radiation on the receiver and its size, the tower height, and the number of heliostats and their distribution. The integrated polygeneration system is studied by first and second law analyses, and its optimization is also developed. Results show that the optimal parameters for the solar field are a solar flux of 549.2 kW/m2, a height tower of 73.71 m, an external receiver of 1.86 m height with a 6.91 m diameter, and a total of 1116 heliostats of 6 m × 6 m. For the integrated polygeneration system, the optimal values of the variables considered are 1437 kPa and 351.2 kPa for the separation pressures of both flash chambers, 753 °C for the gasification temperature, 741.1 °C for the inlet temperature to the turbine, 2.5 and 1.503 for the turbine pressure ratios, 0.5964 for the air–biomass equivalence ratio, and 0.5881 for the CO2 mass flow splitting fraction. Finally, for the optimal system, the thermal efficiency is 38.8%, and the exergetic efficiency is 30.9%.

Chronic inflammatory diseases pose a substantial health challenge globally, significantly contributing to morbidity and mortality. Addressing this issue requires the use of effective anti-inflammatory strategies with fewer side effects than those provoked by currently used drugs. In this study, a range of phytochemicals (phenolic di-caffeoylquinic acid (Di-CQA), flavonoid cyanidin-3,5-diglucoside (Cy3,5DiG), aromatic isothiocyanate sinalbin (SNB) and aliphatic isothiocyanate sulforaphane (SFN)) sourced from vegetables and fruits underwent assessment for their potential anti-inflammatory activity. An in vitro model of human macrophage-like cells treated with a low dose of LPS to obtain a low degree of inflammation that emulates a chronic inflammation scenario revealed promising results. Cell viability and production of the key pro-inflammatory cytokines were assessed in the presence of various phytochemicals. The compounds Di-CQA and Cy-3,5-DiG, within low physiologically relevant doses, demonstrated notable anti-inflammatory effects by significantly reducing the production of key pro-inflammatory cytokines TNF-α and IL-6 without affecting cell viability. These findings underscore the potential of plant-derived bioactive compounds as valuable contributors to the prevention or treatment of chronic inflammatory diseases. These results suggest that these compounds, whether used individually or as part of natural mixtures, hold promise for their inclusion in nutritional interventions designed to mitigate inflammation in associated pathologies.

Resumen: Introducción: la parada cardiaca en la gestante es un reto en la atención extrahospitalaria, y en España disponemos en ese entorno de médicos que podrían hacer cesáreas perimorten. Material y método: inicialmente se evaluaron las lagunas de conocimiento en el manejo de la parada cardiaca (PCR) en gestantes por parte del personal de urgencias extrahospitalarias, para crear un curso semipresencial de simulación de soporte vital avanzado en gestantes (SVA-G). En una segunda fase realizamos un curso para determinar el grado de aprendizaje de conocimientos y habilidades adquirido en soporte vital en el gestante Resultados: previo a la creación del curso, se analizó que el porcentaje de aciertos sobre el manejo de la PCR en las embarazadas era del 54,48%, y el 67,12% de los alumnos manifestó que no estaba lo suficientemente capacitado para hacerlo. En función de esas lagunas creamos el curso de SVA-G. Un total de 88 estudiantes participaron en 5 ediciones del curso. Los conocimientos aumentaron significativamente después del curso, independientemente de la profesión del alumno. Según informaron los alumnos, la satisfacción con el curso, los conocimientos adquiridos y la aplicabilidad de los contenidos a su actividad, fue muy positiva. Conclusión: el curso SVA-G mejora los conocimientos del manejo de la RCP en una embarazada y es un curso útil para el personal que trabaja en urgencias extrahospitalarias. Por ello, tras la creación del curso SVA-G, se incluyó en el catálogo de cursos del Plan Nacional de RCP. Abstract: Introduction: Cardiac arrest in pregnant women is a challenge in out-of-hospital care and in Spain we have doctors in this setting who could perform perimortem caesarean sections. Material and method: Initially, we evaluated the gaps in knowledge in the management of cardiac arrest (CRA) in pregnant women by out-of-hospital emergency personnel in order to create a blended learning course in advanced life support simulation in pregnant women (ALS-G). In a second phase, we conducted a course to determine the degree of learning of knowledge and skills acquired in life support in pregnant women. Results: Prior to the creation of the course, it was analysed that the percentage of success in the management of CPR in pregnant women was 54.48% and 67.12% of the students stated that they were not sufficiently trained to do so. Based on these gaps, we created the VAS-G course. A total of 88 students participated in five editions of the course. Knowledge increased significantly after the course, regardless of the learner's profession. Satisfaction with the course, the knowledge acquired and the applicability of the contents to their activity was reported by the students to be very positive. Conclusion: The SVA-G course improves the knowledge of CPR management in a pregnant woman and is a useful course for personnel working in out-of-hospital emergencies. For this reason, after the creation of the SVA-G course, it was included in the catalogue of courses of the National CPR Plan.

Objective Diagnostic testing is an important tool to combat the COVID-19 pandemic, yet access to and uptake of testing vary widely 3 years into the pandemic. The WHO recommends the use of COVID-19 self-testing as an option to help expand testing access. We aimed to calculate the cost of providing COVID-19 self-testing across countries and distribution modalities.Design We estimated economic costs from the provider perspective to calculate the total cost and the cost per self-test kit distributed for three scenarios that differed by costing period (pilot, annual), the number of tests distributed (actual, planned, scaled assuming an epidemic peak) and self-test kit costs (pilot purchase price, 50% reduction).Setting We used data collected between August and December 2022 in Brazil, Georgia, Malaysia, Ethiopia and the Philippines from pilot implementation studies designed to provide COVID-19 self-tests in a variety of settings—namely, workplace and healthcare facilities.Results Across all five countries, 173 000 kits were distributed during pilot implementation with the cost/test distributed ranging from $2.44 to $12.78. The cost/self-test kit distributed was lowest in the scenario that assumed implementation over a longer period (year), with higher test demand (peak) and a test kit price reduction of 50% ($1.04–3.07). Across all countries and scenarios, test procurement occupied the greatest proportion of costs: 58–87% for countries with off-site self-testing (outside the workplace, for example, home) and 15–50% for countries with on-site self-testing (at the workplace). Staffing was the next key cost driver, particularly for distribution modalities that had on-site self-testing (29–35%) versus off-site self-testing (7–27%).Conclusions Our results indicate that it is likely to cost between $2.44 and $12.78 per test to distribute COVID-19 self-tests across common settings in five heterogeneous countries. Cost-effectiveness analyses using these results will allow policymakers to make informed decisions on optimally scaling up COVID-19 self-test distribution programmes across diverse settings and evolving needs.

This work introduces a novel scheme for driving light-emitting diodes (LEDs) with thermal compensation. The primary objective of the system is to address the issue of emitted light intensity drift caused by temperature variations, with a particular focus on the automotive industry. The developed technique proposes an alternative approach to the traditional thermal approach, which primarily focuses on heat dissipation. In contrast, the presented strategy utilizes a temperature-dependent element, such as a thermistor, to generate a reference current that increases with temperature. The generated current is then amplified by a commercial integrated driver and employed to bias the LEDs. Consequently, the reduction in the emitted light intensity resulting from an increase in the internal temperature of the LED is counterbalanced by an elevation in the bias current. The luminous flux model developed for the proposed system predicts the attainment of stable light intensity across a wide temperature range. The proposed strategy has been applied to three commercial LEDs commonly employed in automotive signal lighting to produce red, yellow, and white light. Experimental results confirm a significant reduction in the thermal dependence of the luminous flux, with reduction factor of temperature dependence ranging between 3.7 and 14.2 for the least and most temperature-sensitive LED models analyzed, respectively.

La COVID 19 irrumpió a finales de 2019 con graves consecuencias a nivel mundial en todos los sectores. El ámbito socioeducativo, caracterizado por trabajar con colectivos en riesgo de exclusión, recibió fuertemente el impacto de la pandemia. Aspectos como la brecha digital o la escasez de recursos dificultaron la atención telemática que se dio en diferentes sectores. Los objetivos del trabajo son conocer como las medidas derivadas de la COVID 19 han impactado en las formas de trabajo en el ámbito socioeducativo en España, con especial incidencia en el uso de las TIC, y elaborar propuestas de mejora derivadas de la situación sobrevenida. Se realiza un estudio cuantitativo, de carácter descriptivo y correlacional, mediante la técnica de encuesta. La muestra es de 818 profesionales de las 17 comunidades autónomas. Los datos son analizados mediante el programa SPSS. Los resultados muestran como en la pandemia por COVID 19 ha generado nuevas formas de organización del trabajo en el ámbito socioeducativo, ha aumentado la carga de trabajo y ha supuesto el trabajo con medios propios. Se concluye con la necesidad de desarrollar la competencia digital de profesionales y usuarios y una mayor dotación de recursos para la intervención socioeducativa.

Abstract We study the quantum cosmology of supersymmetric, homogeneous and isotropic, higher derivative models. We recall superfield actions obtained in previous works and give classically equivalent actions leading to second order equations for the bosons, and first order for the fermions. Upon quantization, the algebra of fermions leads to a multi-component state, which is annihilated by the Hamiltonian and supersymmetric constraint operators. We obtain asymptotic wave functions of the oscillatory type, whose classical limit corresponds to inflationary evolution, and exact exponential wave functions. We use the latter to derive probability distributions of the initial curvature that are compatible with those obtained using the non-supersymmetric model.

Fundamento: la toxoplasmosis adquirida en niños durante los primeros años de vida es la consecuencia de la transmisión por vía oral de esta parasitosis.Objetivo: determinar la prevalencia de infección por Toxoplasma gondii en niños en los primeros años de vida y relacionarlos con variables epidemiológicas de infestación.Métodos: estudio descriptivo y transversal para examinar la presencia de anticuerpos IgG anti-Toxoplasma gondii en niños de uno a seis años de edad en el área rural del municipio Cueto durante el periodo 2020-2021. Se utilizó un muestreo probabilístico por cuotas y se recopilaron variables demográficas y epidemiológicas. Se obtuvo una muestra de 200 niños, a los que se les tomó suero a través de venopunción. Se utilizó la técnica de IFI para determinar la presencia de anticuerpos IgG anti-Toxoplasma gondii y se aplicó la prueba no paramétrica Chi-Cuadrado de Pearson para comprobar hipótesis de investigación.Resultados: la seropositividad a T. gondii fue de un 58 % en la muestra estudiada; se encontró relación entre la infestación y la convivencia con gatos domésticos y con la procedencia del agua. No se encontraron diferencias significativas en la prevalencia de T. gondii en relación con la edad, el sexo, nivel social, cultural y la higiene ambiental, consumo de carnes, frutas y hortalizas, convivencias con animales de corral.Conclusiones: se evidencia seroprevalencia a T. gondii en la población infantil de uno a seis años de edad y su relación con la procedencia del agua y la convivencia con gatos.

Las diferentes formas de comunicar la ciencia es uno de los indicadores cuantitativos de acreditación en Ecuador, el número de publicaciones sigue siendo la forma más efectiva de calcular el impacto de la investigación científica en las instituciones de educación superior. La presente investigación tiene por objetivo proponer una estrategia metodológica de comunicación de la ciencia centrada en aumentar el indicador de publicaciones en el Instituto Superior Tecnológico Bolivariano de Tecnología (ITB). Como método, se utilizó la técnica de Grupo Focal para identificar las principales razones por las cuales los profesores investigadores presentan una tendencia negativa al número de publicaciones anuales. Durante el proceso de recolección y procesamiento de datos, se arribaron a los siguientes resultados: al aplicar la estrategia en las tres etapas se pudo evaluar el impacto de la producción científica y la visibilidad institucional en rankings bibliométricos de los profesionales investigadores del ITB. De esa forma, se llegó a la conclusión de que existe poca motivación para incentivar las publicaciones, baja participación en proyectos de investigación, capacitación insuficiente y excesiva carga docente. Por ello, se creó el plan de acción que debe contribuir el aumento del índice de publicaciones y visibilidad institucional en rankings bibliométricos; así como promover la participación en redes y proyectos de investigación, eventos nacionales e internacionales, entre otros.

Jonatan Valverde Bernal,1 Fina Martínez-Soler,2 Gemma Berga Congost,1,2 José Martínez Pérez,1 Lluis Asmarats,1 Carmen Moreno Arroyo2 1Interventional Cardiology Unit, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 2Department of Fundamental and Clinical Nursing, Faculty of Nursing, Universitat de Barcelona, Hospitalet de Llobregat, Barcelona, SpainCorrespondence: Jonatan Valverde Bernal, Sant Antoni Maria Claret St 167, Hospital de la Santa Creu i Sant Pau, Haemodynamic Unit, Barcelona, 08025, Spain, Tel +34 680 84 35 86, Email jvalverdebernal@gmail.com Fina Martínez-Soler, Feixa Llarga St, Universitat de Barcelona, Hospitalet de Llobregat, Barcelona, 08907, Spain, Tel + 34 660 84 78 07, Email finamartinez@ub.eduBackground: The percutaneous treatment of heart valve diseases carried out in the hemodynamic service is constantly growing. After analyzing the mortality, readmissions, success of the procedure, and complications, several studies support this type of percutaneous procedure. The increase in these procedures has required the creation of multidisciplinary teams and new diagnostic and care circuits, such as presurgical consultations and postsurgical follow-ups. Even so, there is little evidence regarding the effect of these consultations on quality indicators.Purpose: The objective of this study is to evaluate the impact of a program of presurgical and postsurgical nurse interventions (PROCESS-VALVE) on quality indicators of the health of patients undergoing percutaneous valve procedures.Patients and Methods: The influence of presurgical and postsurgical consultations on quality indicators will be evaluated through an ambispective quasi-experimental study. Patients will be recruited at a tertiary-level hospital in Barcelona, Spain. For the control group, data will be collected retrospectively from patients who underwent percutaneous valve procedures but did not receive pre- or postsurgical consultations. The intervention group comprises those patients agreeing to participate in the study and the hemodynamic nurse valve consultation program (PROCESS-VALVE). In addition, we will assess whether a face-to-face postsurgical consultation equally improves quality indicators compared to postsurgical telephone consultation; for this, a sub-study will be carried out comparing face-to-face or telephone postsurgical follow-up by means of a randomized controlled clinical trial with simple blinding in the intervention group.Discussion: This study will generate scientific evidence regarding the impact on quality indicators of a nursing intervention via presurgical and postsurgical consultations. In addition, it will allow us to decide the most appropriate follow-up strategy for this type of patient.Trial Registration: ClinicalTrials.gov NCT05179278, registration date 01/05/2022.Keywords: valvular heart disease, nurse consultation, health indicators, postsurgical follow-up

Abstract Iatrogenic urinary tract injury (IUTI) is a severe complication of emergency digestive surgery. It can lead to increased postoperative morbidity and mortality and have a long-term impact on the quality of life. The reported incidence of IUTIs varies greatly among the studies, ranging from 0.3 to 1.5%. Given the high volume of emergency digestive surgery performed worldwide, there is a need for well-defined and effective strategies to prevent and manage IUTIs. Currently, there is a lack of consensus regarding the prevention, detection, and management of IUTIs in the emergency setting. The present guidelines, promoted by the World Society of Emergency Surgery (WSES), were developed following a systematic review of the literature and an international expert panel discussion. The primary aim of these WSES guidelines is to provide evidence-based recommendations to support clinicians and surgeons in the prevention, detection, and management of IUTIs during emergency digestive surgery. The following key aspects were considered: (1) effectiveness of preventive interventions for IUTIs during emergency digestive surgery; (2) intra-operative detection of IUTIs and appropriate management strategies; (3) postoperative detection of IUTIs and appropriate management strategies and timing; and (4) effectiveness of antibiotic therapy (including type and duration) in case of IUTIs.

This study investigates the effect of daily consumption of a concentrated garlic and onion extract on COVID-19 symptoms among elderly nursing home residents. Volunteers consumed a daily capsule of the concentrated powder rich in organosulfur compounds over 36 weeks during lunch. The incidence and severity of COVID-19 symptoms between the treatment and control groups were compared, along with monitoring the safety of consumption, incidence of other diseases, and medicine usage. The treatment group showed a significant reduction in both the number and severity of COVID-19 symptoms compared to the control group, with no significant adverse effects observed. No significant reduction in symptom duration was detected. This study provides preliminary evidence that concentrated garlic and onion extract may aid in the treatment of COVID-19 among older adults. These findings suggest potential public health benefits, emphasizing the need for further research to explore the immunomodulatory properties of these natural compounds.

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35–23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41–28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice.

A multicenter cross-sectional study was conducted among 245 experienced Spanish paediatricians, who completed an online survey based on clinically relevant topics in nutrition during the first two years of life and their recommendations to parents in daily clinical practice. Most participants advise about the choking risk associated with baby-led weaning (BLW) and more than 60% consider that infants can receive an insufficient variety and quantity of nutrients with this practice. The general opinion is that there is a lack of evidence for delaying the introduction of gluten and other allergenic foods in the complementary feeding of healthy infants. Most participants agree/strongly agree that two servings of dairy products are the adequate daily amount in a diversified diet and 93.4% disagree/strongly disagree with the use of vegetal beverages under 1 year of life. There is a general agreement to avoid added salt and sugar before 12 months of life, the consideration that organic foods do not have a better nutritional profile than non-organic ones, and the limitations of vegetarian diets especially for adequate provision of micronutrients. Overall, there is an adequate knowledge of the new trends by paediatricians and younger ones seemed more in favor of them and interested in receiving more information on most topics.

(1) Background: This study aimed to determine the diagnostic accuracy that optical coherence tomography (OCT) can add to fundus photography (FP) in assessing the condition of the retinal posterior pole. (2) Methods: We conducted two blocks of analysis: First, the posterior pole of each eye was examined using an FP non-mydriatic imaging device. Second, OCT was used in addition to FP. After consolidating the specific diagnostic criteria, the assessments were evaluated using two blinded independent investigation groups (by optometrists, and by ophthalmologists who were considered the gold standard). (3) Results: We calculated the diagnostic accuracy of FP compared to OCT and found that they had similar sensitivity. FP had a slightly higher specificity (p-value: 0.01), and OCT had a higher kappa coefficient with 0.50 (95% CI: 0.46–0.55) vs. 0.39 (95% CI: 0.34–0.45) for FP. (4) Conclusions: On the basis that the role of the optometrist in Spain is not to diagnose but to detect lesions and refer patients to an ophthalmologist, the results of this study support the use of OCT, which provided gradable images in almost all examined eyes (97.5%), compared to FP (73.5%). However, optometrists need a detailed and standardized guide in order to conduct evaluations according to the ophthalmologist’s criteria.

The cancer stem cell (SC) theory proposes that a population of SCs serves as the driving force behind fundamental tumor processes, including metastasis, recurrence, and resistance to therapy. The standard of care for patients with stage III and high-risk stage II colorectal cancer (CRC) includes surgery and adjuvant chemotherapy. Fluoropyrimidines and their combination with oxaliplatin increased the cure rates, being able to eradicate the occult metastatic SC in a fraction of patients. The treatment for unresectable metastatic CRC is based on chemotherapy, antibodies to VEGF and EGFR, and tyrosine-kinase inhibitors. Immunotherapy is used in MSI-H tumors. Currently used drugs target dividing cells and, while often effective at debulking tumor mass, these agents have largely failed to cure metastatic disease. SCs are generated either due to genetic and epigenetic alterations in stem/progenitor cells or to the dedifferentiation of somatic cells where diverse signaling pathways such as Wnt/β-catenin, Hedgehog, Notch, TGF-β/SMAD, PI3K/Akt/mTOR, NF-κB, JAK/STAT, DNA damage response, and Hippo-YAP play a key role. Anti-neoplastic treatments could be improved by elimination of SCs, becoming an attractive target for the design of novel agents. Here, we present a review of clinical trials assessing the efficacy of targeted treatment focusing on these pathways in CRC.

Abstract Recent introduction of monoclonal antibodies targeting immune checkpoints to harness antitumor immunity has revolutionized the cancer treatment landscape. The therapeutic success of immune checkpoint blockade (ICB)-based therapies mainly relies on PD-1/PD-L1 and CTLA-4 blockade. However, the limited overall responses and lack of reliable predictive biomarkers of patient´s response are major pitfalls limiting immunotherapy success. Hence, this reflects the compelling need of unveiling novel targets for immunotherapy that allow to expand the spectrum of ICB-based strategies to achieve optimal therapeutic efficacy and benefit for cancer patients. This review thoroughly dissects current molecular and functional knowledge of BTLA/HVEM axis and the future perspectives to become a target for cancer immunotherapy. BTLA/HVEM dysregulation is commonly found and linked to poor prognosis in solid and hematological malignancies. Moreover, circulating BTLA has been revealed as a blood-based predictive biomarker of immunotherapy response in various cancers. On this basis, BTLA/HVEM axis emerges as a novel promising target for cancer immunotherapy. This prompted rapid development and clinical testing of the anti-BTLA blocking antibody Tifcemalimab/icatolimab as the first BTLA-targeted therapy in various ongoing phase I clinical trials with encouraging results on preliminary efficacy and safety profile as monotherapy and combined with other anti-PD-1/PD-L1 therapies. Nevertheless, it is anticipated that the intricate signaling network constituted by BTLA/HVEM/CD160/LIGHT involved in immune response regulation, tumor development and tumor microenvironment could limit therapeutic success. Therefore, in-depth functional characterization in different cancer settings is highly recommended for adequate design and implementation of BTLA-targeted therapies to guarantee the best clinical outcomes to benefit cancer patients.

Background/Aims The study objective is to investigate the ultrasound features that allow suspecting the presence of submucosal fat deposition, called the fat halo sign (FHS), in the intestinal wall of patients with Crohn’s disease. Methods Computed tomography (CT) examinations over a period of 10 years were reviewed for the presence of the FHS in the bowel wall. A measurement of less than –10 Hounsfield units was regarded as indicative of fat. We included only patients who had undergone ultrasound examinations 3 months before or after CT. The study cohort group comprised 68 patients. Wall and submucosal thickness were measured on longitudinal ultrasound sections. A receiver operating characteristic curve was constructed to determine the best cutoff of ultrasound submucosal wall thickness value for predicting FHS in the bowel wall determined on CT. Results The FHS was present in 22 patients (31%) on CT. There were significant differences between submucosal thickness of patients with FHS and patients without FHS (4.19 mm vs. 2.41 mm). From the receiver operating characteristic curve, a threshold value of 3.1 mm of submucosal thickness had the best sensitivity and specificity to suspect FHS (95.5% and 89.1%, respectively; area under the curve, 0.962), with an odds ratio of 172. All of 16 patients with a submucosal thickness >3.9 mm had FHS. Conclusions FHS in patients with Crohn’s disease can be suspected on ultrasound in cases with marked thickening of the submucosa layer. In these cases, the activity of the disease should be measured by other parameters such as the color Doppler.

Abstract Laparotomy incisions provide easy and rapid access to the peritoneal cavity in case of emergency surgery. Incisional hernia (IH) is a late manifestation of the failure of abdominal wall closure and represents frequent complication of any abdominal incision: IHs can cause pain and discomfort to the patients but also clinical serious sequelae like bowel obstruction, incarceration, strangulation, and necessity of reoperation. Previous guidelines and indications in the literature consider elective settings and evidence about laparotomy closure in emergency settings is lacking. This paper aims to present the World Society of Emergency Surgery (WSES) project called ECLAPTE (Effective Closure of LAParoTomy in Emergency): the final manuscript includes guidelines on the closure of emergency laparotomy.

Abstract Background Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection. Methods A panel of 53 tumor cell lines of different origins was used. The effects of drugs were analyzed by MTT and flow cytometry. Copy number status was determined by FISH and Q-PCR; mRNA expression by nCounter and RT-Q-PCR and protein expression by Western blotting. CRISPR-Cas9 technology was used for gene knock-out (KO) and a doxycycline-inducible pTRIPZ vector for ectopic expression. Finally, in vivo experiments were performed by implanting cultured cells or fragments of tumors into immunodeficient mice. Results Tumor cells and patient-derived xenografts (PDXs) sensitive to AURKB and TTK inhibitors consistently showed high expression levels of BH3-interacting domain death agonist (BID), while cell lines and PDXs with low BID were uniformly resistant. Gene silencing rendered BID-overexpressing cells insensitive to SAC abrogation while ectopic BID expression in BID-low cells significantly increased sensitivity. SAC abrogation induced activation of CASP-2, leading to cleavage of CASP-3 and extensive cell death only in presence of high levels of BID. Finally, a prevalence study revealed high BID mRNA in 6% of human solid tumors. Conclusions The fate of tumor cells after SAC abrogation is driven by an AURKB/ CASP-2 signaling mechanism, regulated by BID levels. Our results pave the way to clinically explore SAC-targeting drugs in tumors with high BID expression.

Abstract Introduction Colombia has 50,912,429 inhabitants, but only 50–70% of the population can effectively access health care services. The emergency room (ER) is a main contributor to the in-hospital care system since up to half of the admissions come through it. Telemedicine has become a tool to facilitate effective access to health care services, improve the timeliness of care, reduce diagnostic variability, and reduce costs associated with health. The aim of this study is to describe the experience of a Distance Emergency Care Program through Telemedicine (TelEmergency) to improve specialist access for patients at the Emergency Room (ER) in low- and medium-level care hospitals in Colombia. Methods An observational descriptive study of a cohort including 1,544 patients during the program’s first two years was conducted. Descriptive statistics were used to analyze the available data. The data are presented with summarized statistics of sociodemographic, clinical, and patient-care variables. Results The study included a total of 1,544 patients, and the majority were adults between 60 and 79 years of age (n = 491, 32%). More than half were men (n = 832, 54%), and 68% (n = 1,057) belonged to the contributory health care regime. The service was requested from 346 municipalities, 70% (n = 1,076) from intermediate and rural settings. The most common diagnoses were related to COVID-19 (n = 356, 22%), respiratory diseases (n = 217, 14%), and cardiovascular diseases (n = 162, 10%). We observed 44% (n = 681) of local admissions either under observation (n = 53, 3%) or hospitalization (n = 380, 24%), limiting the need for hospital transfers. Program operation data revealed that 50% (n = 799) of requests were answered within two hours by the medical staff. The initial diagnosis was modified in 7% (n = 119) of the patients after being evaluated by specialists at the TelEmergency program. Conclusions This study shows the operational data collected during the first two years after the implementation of the TelEmergency program in Colombia, the first of its kind in the country. Its implementation offered specialized timely management of patients at the ER in low- and medium-level care hospitals, where there is no availability of specialized doctors.

Introduction and Objectives: Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) has been recognized as the hepatic component of metabolic syndrome and has become a growing public health concern. Early and accurate detection of MAFLD is crucial for implementing appropriate intervention strategies and preventing progression to serious complications such as liver cirrhosis. We aimed to describe the diagnostic performance of the Hepatic Steatosis Index (HSI) in subjects with MAFLD and compare it with the Homeostatic Model Assessment of Insulin Resistance (HOMA), Waist-to-Hip Ratio (WHR), and Visceral Fat (SECA). Materials and Methods: Retrospective design study. Bioanthropometric, clinical, and biochemical variables were collected. The HSI was calculated using the formula HSI = 8 * ALT/AST + BMI + 2 (if diabetic) + 2 (if female). ROC curves and their areas were generated. Statistical significance was determined at p < 0.05. Results: A total of 585 subjects were evaluated, of whom 279 were classified with MAFLD (65.5% females) and 306 without MAFLD (76.8% females). Subjects with MAFLD exhibited higher values of age, BMI, WHR, HOMA, CAP, and HSI (Table 1). The HSI showed a diagnostic performance with an area under the curve (AUC) of 0.80. A cutoff point of 39.9 was established for the HSI, with a sensitivity of 63%, specificity of 74%, positive predictive value (PPV) of 73%, and negative predictive value (NPV) of 64%. The HSI demonstrated superior diagnostic performance compared to visceral fat (0.70), HOMA (0.70), and WHR (0.66) (Fig 1). Conclusions: The results of this study demonstrate that HOMA, visceral fat, and ICC can be useful as screening strategies in MAFLD. However, the Hepatic Steatosis Index (HSI) showed superior diagnostic performance compared to the other evaluated biomarkers. Therefore, it is suggested that HSI be considered a useful diagnostic tool in MAFLD.

Introduction and Objectives: Leflunomide is a drug used to treat autoimmune diseases. However, despite its therapeutic benefits, adverse effects have been reported after six months of treatment, including liver damage. Materials and Patients: A 19-year-old female from Acayucan, Veracruz, without significant hereditary or family history, drug addiction denied, with a pathological history of hypothyroidism for 2 years and rheumatoid arthritis since the age of 15, treated with leflunomide 20 mg, chloroquine 150 mg, levothyroxine 100 mcg. She presented in October 2022 with nausea, vomiting, postprandial abdominal pain, jaundice. Abdominal ultrasound revealed chronic calculous cholecystitis. Laparoscopic cholecystectomy was performed in December 2022 without complications. After surgical treatment, he persisted with jaundice, alteration of liver function tests of mixed pattern that evolves to cholestatic pattern (R factor 0.2, see Table 1). Non-reactive to viral hepatitis A, B and C, HIV, negative antibodies ANA, AML, AMA, anti-DNAds, anti-Smith, anti-Rho, complement C3 145 and C4 33. Cholangiography, with hepatomegaly, diffuse hepatic steatosis without evidence of biliary lesions. Liver biopsy showed features of portal and lobular hepatitis, intracytoplasmic and intracanalicular cholestasis, macrovesicular steatosis, and F2 fibrosis according to METAVIR (Fig. 1), which were not consistent with autoimmune or viral disease. RUCAM score with possible relation to hepatoxicity (4 points), so it is considered drug-induced liver injury (leflunomide). Results: Leflunomide was discontinued and treatment was adjusted to chloroquine 150 mg and prednisone 50 mg. Clinical and biochemical improvement was observed. Conclusions: This case highlights the importance of suspecting DILI in patients treated with potentially hepatotoxic drugs and with alterations in liver biochemistry. It is a rare disease for which there are no specific markers. Therefore, liver biopsy is a useful tool for early diagnosis.