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Background: Ophthalmoplegic migraine (OM) is an uncommon variant of migraine characterised by headache and cranial nerve palsy, posing significant diagnostic and therapeutic challenges. Objective: This study aimed to describe an extremely rare OM variant with a partial therapeutic response. Clinical Case: A 34-year-old pregnant woman in gestational week 19.1 (G6P2A3) with a history of three consecutive spontaneous abortions presented at the emergency services with insidious onset and mild-to-moderate-intensity pulsatile bifrontal headache for 15 days, and the positional changes exacerbated this. At peak intensity, she experienced nausea, vomiting, tinnitus, and photophobia without phonophobia or osmophobia, prompting multiple visits to the emergency department. Despite a broad range of treatments, including intravenous fluids, analgesia, pericranial blocks, and preventive management, there was a non-significative improvement in the symptomatology described above. However, spontaneous resolution of this clinical picture was observed during the postpartum period. Results: This case highlights the complexity of ophthalmoplegic migraine, especially in the context of pregnancy, and raises questions about the underlying pathophysiological mechanisms. The absence of structural lesions on neuroimaging and postpartum resolution suggests a potential association with the hormonal and physiological changes associated with pregnancy. Conclusions: Despite limited scientific evidence, this report contributes to expanding the knowledge of this rare entity and emphasises the importance of a multidisciplinary approach to its management.

Triple negative breast cancer (TNBC) is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better prognosis and higher probability to achieve pathological complete response. Here, we explore the potential role of stromal TILs level and composition as a prognostic and predictive biomarker in TNBC. 195 Tumor biospecimens from patients diagnosed with TNBC were included. Stromal TILs (sTILs), positive CD4/CD8 cells were evaluated. Differences in clinic-pathological characteristics according to immune infiltration were assessed. The predictive and prognostic value of immune infiltration was analyzed by multivariate models. Higher immune infiltration was observed in patients with favorable clinical-pathological features. Survival analysis showed that longer overall survival times were observed in patients with a higher infiltration of sTILs (p = 0.00043), CD4 + (p = 0.0074) and CD8 + (p = 0.008). In the multivariate analysis, low levels of sTILs were found to be associated with a higher mortality hazard (HR: 1.59, 95% CI 1.01-2.48). CD4 and CD8 immune infiltration were associated with higher odds for pathological complete response (OR: 1.20, 95% CI 1.00-1.46, OR: 1.28, 1.02-1.65, respectively). Our results suggest that immune infiltration could be used as a prognostic marker for overall survival in TNBC patients.

Edentulous patients with history of cleft palate and severe maxillary atrophy are challenging patients to rehabilitate through an oral approach. The difficulty of rehabilitating these patients lies in the unusual anatomy they present and the alteration of the vascular supply of local tissues caused by the previous performed surgeries, along with other causes. This report describes the successful dental rehabilitation with zygomatic implants of a patient with complete bilateral cleft palate who was edentulous and had severe maxillary atrophy.

The increasing economic activity, population growth and urbanisation are placing increasing stress on Europe’s freshwater resources. The European Union's Water Framework Directive (WFD) aimed to establish measures to foster efficient use of this valuable natural resource while simultaneously protecting the environment. This study allows for an assessment of the Directive's application of public policies to a natural resource, assuming that the efficiency of water use is measured by water productivity. For the purposes of this investigation, purely economic variables and specific variables pertaining to the implementation of the WFD will be considered. The final econometric model indicates that variables with a positive impact, including research and development (R&D) expenditure and the governance index, necessitate the updating of facilities, the implementation of public control of the resource, and the encouragement of citizen interest in influencing EU policies. Conversely, variables with a negative impact, including population density and water consumption, indicate that as the utilization of a given resource intensifies, the efficacy of that utilization diminishes. The analysis by country indicates that the northern and more industrialised economies have more efficient water use levels. The evolution over time demonstrates that the WFD is being implemented more extensively in regions where it is most needed, resulting in increased productivity values in areas where they are currently lower.

The replication-defective adeno-associated virus (AAV) is extensively utilized as a research tool or vector for gene therapy. The production process of AAV remains intricate, expensive, and mechanistically underexplored. With the aim of enhancing AAV manufacturing efficiencies in mammalian cells, we revisited the questions and optimization surrounding the requirement of the various adenoviral helper genes in enabling AAV production. First, we refined the minimal set of adenoviral genes in HEK293 AAV production to E2A, L4-22K/33K, and VA RNA I. These findings challenge the previously accepted necessity of adenoviral E4orf6 in AAV production. In addition, we identified L4-22K genes as crucial helpers for AAV production. Next, a revised minimal adenoviral helper plasmid comprising E2A, L4-22K, and VA RNA I genes was designed and demonstrated to yield high titer and potent AAV preps in HEK293 transient transfection. Lastly, stable packaging cells harboring inducible E2A and L4-22K genes were shown to maintain AAV production yields comparable to transient transfection over a culture period of ∼10 weeks. Combined, these findings further our understanding of adenoviral helper function in mammalian AAV production and provide novel plasmid and cell-line reagents with an improved safety profile for potential broad applicability in the research and gene therapy community.

Participatory Geographic Information Systems (PGIS) combine geographic information with citizen or community participation to integrate local knowledge with issues related to natural resource management, territorial planning, and environmental pollution that are fundamental to decision-making. However, the current challenge is involving and educating the population to succeed in the PGIS. For this reason, a PGIS system was implemented to identify areas with higher solid waste accumulation and to determine the accuracy of the reports made by the trained population. A participatory platform was implemented using ArcGIS (Online, Desktop, Survey123, Web App Builder, and Experience Builder) for daily reporting of areas contaminated by solid waste. The information obtained for two months was used to generate Kernel density maps, which made it possible to identify the most contaminated regions of the city. A total of 2778 areas contaminated by solid waste were reported during the evaluation period, where 53 % (1486) presented a low level of contamination (area less than 1 m2), 16 % (442) had a medium level of contamination (area equal to 1 m2) and 31 % (850) reported a high level of contamination (area greater than 1 m2). The results allowed the generation of Kernel density maps showing 24 areas classified as 'Extremely High'. Saturdays and Sundays reported higher contamination concerning the other days of the week. The accumulation of contaminants is mainly in the water bodies located in the study area.

IntroductionB-cell acute lymphoblastic leukemia (B-ALL) in adults often presents a poor prognosis. ID1 and ID3 genes have been identified as predictors of poor response in Colombian adult B-ALL patients, contributing to cancer development. In various cancer models, these genes have been associated with immune regulatory populations within the tumor immune microenvironment (TIME). B-ALL progression alters immune cell composition and the bone marrow (BM) microenvironment, impacting disease progression and therapy response. This study investigates the relationship between ID1 and ID3 expression, TIME dynamics, and immune evasion mechanisms in adult B-ALL patients. MethodsThis exploratory study analysed BM samples from 10 B-ALL adult patients diagnosed at the National Cancer Institute of Colombia. First, RT-qPCR was used to assess ID1 and ID3 expression in BM tumour cells. Flow cytometry characterised immune populations in the TIME. RNA-seq evaluated immune genes associatedwith B-ALL immune response, while xCell and CytoSig analysed TIME cell profiles and cytokines. Pathway analysis, gene ontology, and differential gene expression (DEGs) were examined, with functional enrichment analysis performed using KEGG ontology.ResultsPatients were divided into two groups based on ID1 and ID3 expression, namely basal and overexpression. A total of 94 differentially expressed genes were identified between these groups, with top overexpressed genes associated with neutrophil pathways. Gene set enrichment analysis revealed increased expression of genes associated with neutrophil degranulation, immune response-related neutrophil activation, and neutrophil-mediated immunity. These findings correlated with xCell data. Overexpression group showed significant differences in neutrophils, monocytes and CD4+ naive T cells compared to basal group patients. Microenvironment and immune scores were also significantly different, consistent with the flow cytometry results. Elevated cytokine levels associated with neutrophil activation supported these findings. Validation was performed using the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) TCGA B-ALL cohorts.DiscussionThese findings highlight significant differences in ID1 and ID3 expression levels and their impact on TIME populations, particularly neutrophil-related pathways. The results suggest a potential role for ID1 and ID3 in immune evasion in adult B-ALL, mediated through neutrophil activation and immune regulation.

El libro escrito por William Enrique Cepeda Peña es un estudio detallado sobre los eclipses de Sol y Luna en Colombia, que incluye un cálculo preciso de las zonas de penumbra y sombra, así como tablas de predicción hasta el año 2100. Está dividido en cuatro partes que ofrecen una explicación exhaustiva de estos fenómenos astronómicos, basada en investigaciones realizadas en el Observatorio Astronómico Nacional.

Resumen: Introducción: La presión positiva continua en la vía aérea (CPAP) constituye el tratamiento más eficaz en la apnea obstructiva del sueño (AOS). Para lograr la adaptación al equipo se utilizan de forma mayoritaria sistemas de titulación automáticos (TA). Las CPAP domiciliarias, permiten la telemonitorización (TM) de los mismos parámetros que nos reportan los sistemas de TA, pero con acceso a todas las horas de uso de forma continua. Bajo esta premisa, nos planteamos un estudio sobre la potencial validez de la TM de las CPAP domiciliarias como sistema de titulación, su impacto directo en la adecuada adaptación (AD) al equipo y de forma secundaria en los recursos sanitarios empleados para lograrlo. Material y métodos: Estudio observacional con 318 pacientes con AOS a los que titulamos mediante TM para lograr la AD al CPAP. Los pacientes con AOS son reclutados de forma consecutiva y evaluados en el 1°, 3° y 6° mes de inicio de tratamiento. Los resultados se comparan con un grupo histórico de 307 pacientes con AOS en los que se logró la AD al CPAP mediante TA. Secundariamente evaluamos el impacto en los recursos sanitarios requeridos. Resultados: Los pacientes con AOS en los que iniciamos tratamiento con CPAP y TM durante los seis primeros meses, muestran una tasa de AD similar al grupo histórico titulado mediante TA con un menor uso de recursos en el grupo de TM. Conclusión: Los datos que nos reporta la TM de las CPAP domiciliarias permiten titular y lograr una AD similar a la TA en pacientes no complejos. Abstract: Introduction: Continuous Positive Airway Pressure (CPAP) constitutes the most effective treatment for Obstructive Sleep Apnea (OSA). Automatic titration systems (ATS) are predominantly used to achieve adaptation to the equipment. Home CPAP devices allow telemonitoring (TM) of the same parameters as those provided by ATS but with access to continuous usage data. Under this premise, we conducted a study on the potential validity of TM for home CPAP devices as a titration system, its direct impact on proper adaptation (AD) to the equipment, and secondarily on the healthcare resources employed to achieve it. Material and methods: An observational study involving 318 patients with OSA who were titrated using TM to achieve AD to CPAP. Patients with OSA were consecutively recruited and evaluated at 1, 3, and 6 months after initiating treatment. Results were compared with a historical group of 307 patients with OSA who achieved AD to CPAP using ATS. Additionally, we assessed the impact on required healthcare resources. Results: Patients with OSA who initiated CPAP treatment with TM over the first six months showed a similar AD rate compared to the historical group titrated using ATS, with lower resource usage in the TM group. Conclusion: Data provided by TM of home CPAP devices allow for titration and achieving similar AD as with ATS in non-complex patients.

Objective. To establish the diagnostic value of lung ultrasound (LUS) in patients with rheumatoid arthritis (RA) for the detection of interstitial lung disease (ILD). Methods. A cross-sectional study was performed. Consecutive patients with RA (American College of Rheumatology/European League Against Rheumatism 2010 criteria) who had a chest high-resolution computed tomography (HRCT) performed within 12 months before inclusion, regardless of symptomatology, were included. Demographic, clinical, laboratory, and pharmacological data were recorded. Each patient underwent a LUS with assessment of B-lines (BL) and pleural irregularities (PI). HRCT was considered the gold standard for the confirmatory diagnosis of ILD. Receiver operating characteristic (ROC) curves were calculated to test the ability of LUS findings (BL and PI) in discriminating patients with ILD. Results. A total of 104 RA patients were included, of which 21.8% had ILD. Patients with ILD had more BL (median 26 versus 1, p

Abstract Much of nutrition research has been conventionally based on the use of simplistic in vitro systems or animal models, which have been extensively employed in an effort to better understand the relationships between diet and complex diseases as well as to evaluate food safety. Although these models have undeniably contributed to increase our mechanistic understanding of basic biological processes, they do not adequately model complex human physiopathological phenomena, creating concerns about the translatability to humans. During the last decade, extraordinary advancement in stem cell culturing, three‐dimensional cell cultures, sequencing technologies, and computer science has occurred, which has originated a wealth of novel human‐based and more physiologically relevant tools. These tools, also known as “new approach methodologies,” which comprise patient‐derived organoids, organs‐on‐chip, multi‐omics approach, along with computational models and analysis, represent innovative and exciting tools to forward nutrition research from a human‐biology‐oriented perspective. After considering some shortcomings of conventional in vitro and vivo approaches, here we describe the main novel available and emerging tools that are appropriate for designing a more human‐relevant nutrition research. Our aim is to encourage discussion on the opportunity to explore innovative paths in nutrition research and to promote a paradigm‐change toward a more human biology‐focused approach to better understand human nutritional pathophysiology, to evaluate novel food products, and to develop more effective targeted preventive or therapeutic strategies while helping in reducing the number and replacing animals employed in nutrition research.

Introducción. Mycobacterium chelonae y los complejos Mycobacterium avium y M. abscessus, son agentes patógenos emergentes causantes de micobacteriosis. El tratamiento de esta infección depende de la especie y la subespecie identificadas. Los fármacos de elección son los macrólidos y aminoglucósidos, contra los cuales se ha reportado resistencia; por esta razón, el determinar el perfil de sensibilidad le permite al médico tratante comprender mejor el pronóstico y la evolución de estas infecciones. Objetivo. Describir los perfiles de sensibilidad ante macrólidos y aminoglucósidos, de los cultivos identificados como complejo Mycobacterium avium, complejo M. abscessus o especie M. chelonae, en el Laboratorio Nacional de Referencia de Micobacterias durante los años 2018 a 2022. Materiales y métodos. Se llevó a cabo un estudio descriptivo del perfil de sensibilidad a macrólidos y aminoglucósidos, de los cultivos identificados como complejo M. avium, complejo M. abscessus o M. chelonae, mediante la metodología GenoType® NTM-DR. Resultados. Los cultivos del complejo M. avium fueron 159 (47,3 %), de los cuales, 154 (96,9 %) fueron sensibles y 5 (3,1 %) resistentes a los macrólidos; todos fueron sensibles a los aminoglucósidos. Del complejo M. abscessus se estudiaron 125 (37,2 %) cultivos, 68 (54,4 %) resultaron sensibles y 57 (45,6 %) resistentes a los macrólidos; solo un cultivo (0,8 %) fue resistente a los aminoglucósidos. De M. chelonae se analizaron 52 cultivos (15,5 %), todos sensibles a los macrólidos y aminoglucósidos. Conclusiones. En las tres especies de micobacterias estudiadas, la resistencia contra la amikacina fue la menos frecuente. La identificación de las subespecies y los perfiles de sensibilidad permiten instaurar esquemas de tratamiento adecuados, especialmente en las micobacteriosis causadas por M. abscessus.

Human adenovirus (HAdV) type F41 has been identified as a possible cause of the non-A-to-E hepatitis outbreak. This study uses wastewater monitoring to track HAdV F40 and F41, supporting clinical investigations and providing insights into the pathogen’s role in the outbreak. Given the limited clinical monitoring in Sweden of HAdV-F40/41, this approach also helps estimate the true infection burden of this pathogen during the outbreak.This study developed three qPCR assays for the hexon, penton, and fiber genes of HAdV F40 and F41. The hexon assay was F41-specific, while the fiber assay detected multiple HAdV-F strains. Comprehensive monitoring of HAdV-F40/41 levels in Stockholm’s wastewater was conducted over 1.5 years, capturing the period before, during, and after the outbreak. A significant infection wave was observed in spring 2022, with strains beyond lineage 2 contributing to the outbreak. Moreover, simultaneous SARS-CoV-2 surveillance revealed that HAdV-F infections peaked at different times from COVID-19, but the HAdV-F wave aligned with the relaxation of pandemic restrictions. These findings offer valuable insights for future HAdV-F investigations and confirm its role in the non-A-to-E hepatitis outbreak.

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), long COVID (LC) and post-COVID-19 vaccine syndrome show similarities in their pathophysiology and clinical manifestations. These disorders are related to viral or adjuvant persistence, immunological alterations, autoimmune diseases and hormonal imbalances. A developmental model is postulated that involves the interaction between immune hyperactivation, autoimmune hypophysitis or pituitary hypophysitis, and immune depletion. This process might begin with a deficient CD4 T-cell response to viral infections in genetically predisposed individuals (HLA-DRB1), followed by an uncontrolled immune response with CD8 T-cell hyperactivation and elevated antibody production, some of which may be directed against autoantigens, which can trigger autoimmune hypophysitis or direct damage to the pituitary, resulting in decreased production of pituitary hormones, such as ACTH. As the disease progresses, prolonged exposure to viral antigens can lead to exhaustion of the immune system, exacerbating symptoms and pathology. It is suggested that these disorders could be included in the autoimmune/adjuvant-induced inflammatory syndrome (ASIA) because of their similar clinical manifestations and possible relationship to genetic factors, such as polymorphisms in the HLA-DRB1 gene. In addition, it is proposed that treatment with antivirals, corticosteroids/ginseng, antioxidants, and metabolic precursors could improve symptoms by modulating the immune response, pituitary function, inflammation and oxidative stress. Therefore, the purpose of this review is to suggest a possible autoimmune origin against the adenohypophysis and a possible improvement of symptoms after treatment with corticosteroid replacement therapy.

In the last decades, the world population and demand for any kind of product have grown exponentially. The rhythm of production to satisfy the request of the population has become unsustainable and the concept of the linear economy, introduced after the Industrial Revolution, has been replaced by a new economic approach, the circular economy. In this new economic model, the concept of “the end of life” is substituted by the concept of restoration, providing a new life to many industrial wastes. Leaves are a by-product of several agricultural cultivations. In recent years, the scientific interest regarding leaf biochemical composition grew, recording that plant leaves may be considered an alternative source of bioactive substances. Plant leaves’ main bioactive compounds are similar to those in fruits, i.e., phenolic acids and esters, flavonols, anthocyanins, and procyanidins. Bioactive compounds can positively influence human health; in fact, it is no coincidence that the leaves were used by our ancestors as a natural remedy for various pathological conditions. Therefore, leaves can be exploited to manufacture many products in food (e.g., being incorporated in food formulations as natural antioxidants, or used to create edible coatings or films for food packaging), cosmetic and pharmaceutical industries (e.g., promising ingredients in anti-aging cosmetics such as oils, serums, dermatological creams, bath gels, and other products). This review focuses on the leaves’ main bioactive compounds and their beneficial health effects, indicating their applications until today to enhance them as a harvesting by-product and highlight their possible reuse for new potential healthy products.

Relacionar el patrimonio cultural y la geología de un territorio permite acercar a la población esta ciencia, que, en la mayoría de los casos, es menos conocida. En los Geoparques Unesco la interacción con la población y las entidades locales es fundamental para establecer proyectos de desarrollo y conservación, sobre todo en zonas despobladas. Por este motivo las actividades de divulgación son esenciales. Este trabajo presenta dos talleres realizados en dos iglesias, situadas en el Valle de Valdelucio del Geoparque Unesco Las Loras, como ejemplo de divulgación geológica en torno al patrimonio cultural en una zona con alta tasa de despoblación. Este tipo de actividades ofrece a los lugareños y visitantes una perspectiva del entorno novedosa, geológica, que compagina con el patrimonio cultural y realza el valor de la zona.

Resumen: Este trabajo se propone un análisis comparativo de las actividades de lectura en dos asignaturas del primer año de la educación secundaria argentina: Prácticas del Lenguaje (PDL) y Ciencias Sociales (CS). Se grabaron en audio ocho clases, cuatro de cada uno de los espacios curriculares. Se analizaron de acuerdo con propuestas teóricas preexistentes que permiten segmentar las observaciones en diferentes unidades, caracterizar los tipos y funciones de lecturas y las estrategias promovidas. En las sesiones de PDL fue más frecuente la lectura como actividad típica de aula y se realizó poniendo en juego mayor variedad de estrategias que en CS. La lectura colectiva genuina mental predominó en PDL, mientras que en CS prevaleció la lectura por parte de las profesoras con comentarios. Los resultados permiten introducir reflexiones relativas a las intervenciones docentes en materia de lectura según la asignatura escolar y los distintos desafíos que supone su enseñanza.

BackgroundBreast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry.MethodsGenotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region.ResultsWe replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations.ConclusionsThe rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region.ImpactThese results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.

This paper is based on a review of studies focusing on student autonomy in early childhood, primary, and secondary education in Spain published in the last 10 years. Autonomy is defined as the capacity of individuals to act in a self-determined way. Educational institutions play a key role in the development of autonomy through experience, and students demonstrate more autonomy in learning when they are older. The method used in this paper consists of an overview of empirical studies from different databases and the application of three pre-defined filters. A total of 41 studies is analysed and critically assessed in relation to (1) the area of knowledge and level of schooling, (2) the definition of autonomy, (3) the method used, and (4) the elements influencing student autonomy. Results indicate that (1) physical education in secondary education is the most researched area, (2) most studies have defined autonomy and used self-determination theory as a framework for measuring student autonomy, (3) the majority of studies have used quantitative methods and a student sample, and (4) autonomy support provided by teachers positively influences student autonomy. In addition, the results show that intrinsic elements, such as the development of stable individual identity and psychological resources, enhance student autonomy. The paper concludes that future research should be aimed at a more specific conceptualisation of student autonomy to be assessed, measured, and promoted in different international educational environments and areas of knowledge.