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Summary: Background: Pseudomonas aeruginosa is a major cause of hospital-acquired and chronic infections, characterised by an extraordinary capacity to develop antimicrobial resistance through the selection of chromosomal mutations, leading to treatment failure. Here, we designed and tested a hybridisation-based capture system for the enrichment of genes of interest before sequencing to monitor resistant populations genomics directly from clinical samples. Methods: A panel for enrichment before sequencing of close to 200 genes related to P. aeruginosa antimicrobial resistance, multilocus sequence typing, mutability or virulence was designed, synthesised (KAPA HyperCap, Roche) and initially validated in vitro using a multidrug-resistant ST175 isolate and representative isolates from major P. aeruginosa clades. In vivo testing included ventilator associated pneumonia by MDR P. aeruginosa in ICU (3–10 sequential samples from 3 patients) and chronic respiratory infection by hypermutable P. aeruginosa in cystic fibrosis (8 sequential samples from a single patient covering a 4-year period). Results from direct sequencing with the enrichment panel were compared with those of whole genome sequencing (WGS) and phenotypic profiling of 10 isolated colonies per sample. Findings: In vitro assays confirmed the selectivity of the enrichment panel and the correct identification of the vast mutational resistome of ST175, including specific mutations even when introduced in a 1:100 proportion. In vivo performance was at least equivalent to sequencing 10 colonies per sample, including the accurate identification of the sequence types and the basal and acquired mutational resistome. To note, specific resistance mutations, such as those in ampC leading to resistance to novel β-lactams, could be traced even at frequencies of 1%. Moreover, the coselection of mutator populations and antibiotic resistance mutations, predicted in theoretical and in vitro studies, was evidenced in vivo. Interpretation: This proof-of-concept study demonstrates that resistance genomics of P. aeruginosa can be analysed directly from clinical samples, determining not only a considerable reduction in turnaround time and cost from a diagnostics perspective, but also an unprecedented potency for accurate monitoring of in vivo population dynamics in bacterial infections. Funding: Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU.

We aim to evaluate the incidence of incontinence following laser endoscopic enucleation of the prostate (EEP) comparing en-bloc (Group 1) versus 2-lobe/3-lobe techniques (Group 2). We performed a retrospective review of patients undergoing EEP for benign prostatic enlargement in 12 centers between January 2020 and January 2022. Data were presented as median and interquartile range (IQR). Univariable and multivariable logistic regression analysis was performed to evaluate factors associated with stress urinary incontinence (SUI) and mixed urinary incontinence (MUI). There were 1711 patients in Group 1 and 3357 patients in Group 2. Patients in Group 2 were significantly younger (68 [62–73] years vs 69 [63–74] years, P = 0.002). Median (interquartile range) prostate volume (PV) was similar between the groups (70 [52–92] ml in Group 1 vs 70 [54–90] ml in Group 2, P = 0.774). There was no difference in preoperative International Prostate Symptom Score, quality of life, or maximum flow rate. Enucleation, morcellation, and total surgical time were significantly shorter in Group 1. Within 1 month, overall incontinence rate was 6.3% in Group 1 versus 5.3% in Group 2 (P = 0.12), and urge incontinence was significantly higher in Group 1 (55.1% vs 37.3% in Group 2, P < 0.001). After 3 months, the overall rate of incontinence was 1.7% in Group 1 versus 2.3% in Group 2 (P = 0.06), and SUI was significantly higher in Group 2 (55.6% vs 24.1% in Group 1, P = 0.002). At multivariable analysis, PV and IPSS were factors significantly associated with higher odds of transient SUI/MUI. PV, surgical time, and no early apical release technique were factors associated with higher odds of persistent SUI/MUI.

Background: The need for frequent blood glucose (BG) monitoring and the inconveniences associated with self-monitoring of BG (SMBG) have driven the development of non-invasive approaches. Methods: This prospective study aimed to investigate the accuracy of glucose level calculation using the near-infrared spectroscopy (NIRS) technology Glucube® system. People with Type 1 diabetes, Type 2 diabetes, prediabetes, and normal glucose metabolism were included. Over one week, individuals performed glucose measurements with the Glucube® system and capillary blood fingersticks with a standard glucometer (Ascensia Contour® Next). To assess the impact of the improvement in dexterity, the accuracy variables were compared with the point-of-care (POC) glucometer Accu-Chek® Inform II in a one-week sub-study. Results: Overall, 105 subjects (mean age 53.8 ± 13.8 years, 50.5% female) participated, resulting in 1914 paired glucose measurements between 49 and 331 mg/dL. Total mean absolute relative difference (MARD) was 20.3%, MARD for values >100 mg/dL was 18.3%, and mean absolute deviation (MAD) for values p = 0.068). The percentages within Zone A were 51.6 vs. 61.2%, Zone B 46.8 vs. 33.9%, and Zone C 1.6 vs. 4.8%, and the sum of Parkes Zones A+B was 98.4 vs. 95.2% (p = 0.311) for day 1 and day 8, respectively. Conclusions: Glucube® is a novel non-invasive system based on NIRS technology for monitoring blood glucose levels. Its promising capabilities support further research.

Abstract DNA topoisomerase I (TOP1) removes torsional stress by transiently cutting one DNA strand. Such cuts are rejoined by TOP1 but can occasionally become abortive generating permanent protein-linked single strand breaks (SSBs). The repair of these breaks is initiated by tyrosyl-DNA phosphodiesterase 1 (TDP1), a conserved enzyme that unlinks the TOP1 peptide from the DNA break. Additionally, some of these SSBs can result in double strand breaks (DSBs) either during replication or by a poorly understood transcription-associated process. In this study, we identify these DSBs as a source of genome rearrangements, which are suppressed by TDP1. Intriguingly, we also provide a mechanistic explanation for the formation of chromosomal translocations unveiling an error-prone pathway that relies on the MRN complex and canonical non-homologous end-joining. Collectively, these data highlight the threat posed by TOP1-induced DSBs during transcription and demonstrate the importance of TDP1-dependent end-joining in protecting both gene transcription and genome stability.

Summary: Background: Hyperglycaemia is an early and frequent adverse event during alpelisib treatment. METALLICA aimed to evaluate prophylactic metformin to prevent or reduce hyperglycaemia occurrence in patients with HR+/HER2−/PIK3CA-mutated advanced breast cancer (ABC). Methods: Between August 13th, 2020 and March 23rd, 2022, this 2-cohort, phase 2, multicentre, single-arm trial (NCT04300790) enrolled patients with HR+/HER2−/PIK3CA-mutated ABC: cohort A, normal glycaemia (fasting plasma glucose

Chondrosarcoma (CS) is a malignant bone tumor arising from cartilage-producing cells. The conventional subtype of CS typically develops within a dense cartilaginous matrix, creating an environment deficient in oxygen and nutrients, necessitating metabolic adaptation to ensure proliferation under stress conditions. Although ketone bodies (KBs) are oxidized by extrahepatic tissue cells such as the heart and brain, specific cancer cells, including CS cells, can undergo ketolysis. In this study, we found that KBs catabolism is activated in CS cells under nutrition-deprivation conditions. Interestingly, cytosolic β-hydroxybutyrate dehydrogenase 2 (BDH2), rather than mitochondrial BDH1, is expressed in these cells, indicating a specific metabolic adaptation for ketolysis in this bone tumor. The addition of the KB, β-Hydroxybutyrate (β-HB) in serum-starved CS cells re-induced the expression of BDH2, along with the key ketolytic enzyme 3-oxoacid CoA-transferase 1 (OXCT1) and monocarboxylate transporter-1 (MCT1). Additionally, internal β-HB production was quantified in supplied and starved cells, suggesting that CS cells are also capable of ketogenesis alongside ketolysis. These findings unveil a novel metabolic adaptation wherein nutrition-deprived CS cells utilize KBs for energy supply and proliferation.

En recientes estudios realizadas para evaluar pacientes con patología vascular, la importancia de la aplicación de las angioTAC 3D ha venido siendo reportada sucesivamente por distintos investigadores, Harbaugh (3) en 1995 y luego Zouaoui (5) en 1997.

El Anejo Nacional al Eurocódigo 8 prohíbe el uso de vigas planas de hormigón para sismicidad media y alta, y tanto NCSE-02 como la norma italiana NTC impedían su proyecto en ductilidad alta, por desventajas como: transmisión deficiente de esfuerzos al pilar y menor rigidez, ductilidad, disipación, resistencia de nudos y jerarquía pilar-viga. Esta tendencia mediterránea es opuesta a la europea e internacional, donde se permiten las vigas planas con límite de anchura y suficiente sobredimensionando de pilares para garantizar la rigidez lateral. La revisión normativa y experimental sugiere que la limitación de ancho garantiza la transmisión y disipación, mientras que la realización de dos estudios analíticos apunta a que el incremento de sobrerresistencia y ductilidad causados por el engrosamiento de pilares garantiza una capacidad global al menos equiparable a los pórticos de vigas de canto, sugiriendo que el uso de vigas planas podría ser una opción en zona sísmica.

Abstract Chirality or handedness of a material can be used as an order parameter to uncover the emergent electronic properties for quantum information science. Conventionally, chirality is found in naturally occurring biomolecules and magnetic materials. Chirality can be engineered in a topological polar vortex ferroelectric/dielectric system via atomic-scale symmetry-breaking operations. We use four-dimensional scanning transmission electron microscopy (4D-STEM) to map out the topology-driven three-dimensional domain walls, where the handedness of two neighbor topological domains change or remain the same. The nature of the domain walls is governed by the interplay of the local perpendicular (lateral) and parallel (axial) polarization with respect to the tubular vortex structures. Unique symmetry-breaking operations and the finite nature of domain walls result in a triple point formation at the junction of chiral and achiral domain walls. The unconventional nature of the domain walls with triple point pairs may result in unique electrostatic and magnetic properties potentially useful for quantum sensing applications.

In the original publication [...]

Background: A study to assess the glucose levels of people with type 1 diabetes (T1D) overnight, based on the insulin type and timing. Methods: A real-world, retrospective study of T1D, using multiple daily insulin injections. Continuous glucose monitoring and insulin injection data were collected for ten hours after dinner using the Insulclock® connected cap. Meal events were identified using the ROC detection methodology. The timing of the rapid insulin, second injections, and the type of insulin analogs used, were evaluated. Results: The nocturnal profiles (n = 775, 49 subjects) were analyzed. A higher glucose AUC of over 180 mg/dL was observed in subjects with delayed injections (number; %; mg/dL × h): −45–15 min (n = 136; 17.5%, 175.9 ± 271.0); −15–0 min (n = 231; 29.8%, 164.0 ± 2 37.1); 0 + 45 min (n = 408; 52.6%, 203.6 ± 260.9), (p = 0.049). The use of ultrarapid insulin (FiAsp®) (URI) vs. rapid insulin (RI) analogs was associated with less hypoglycemia events (7.1 vs. 13.6%; p = 0.005) and TBR70 (1.7 ± 6.9 vs. 4.6 ± 13.9%; p = 0.003). Users of glargine U300 vs. degludec had a higher TIR (70.7 vs. 58.5%) (adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n = 144, 18.6%) was associated with a higher number of hypoglycemia events (18.1 vs. 9.5%; p = 0.003), TBR70 (5.5 ± 14.2 vs. 3.0 ± 11.1%; p = 0.003), a glucose AUC of over 180 mg/dL (226.1 ± 257.8 vs. 178.0 ± 255.3 mg/dL × h; p = 0.001), and a lower TIR (56.0 ± 27.4 vs. 62.7 ± 29.6 mg/dL × h; p = 0.004). Conclusion: The dinner rapid insulin timing, insulin type, and the use of correction injections affect the nocturnal glucose profile in T1D.

The Cadafresnas granites and granitoid breccias (Peña do Seo, W of León) are small post-tectonic stocks of Variscan age related to W-Sn mineralizations. According to their mineralogical geochemical characteristics, they are classified as granites-syenogranites, granodiorites and granitoids rich in quartz, of peraluminous/metaluminous composition. The Rb-Ba-Sr relationships allow assigning a metapelitic source for the granites and a metagreywacke source for the granitoid breccias. Using geochemical modeling (partial melting), the contribution of these sources to explain the Ba, W and Sn contents of the granites and granite breccias is investigated. The results indicate that the partial melting of these lithologies explains part of the content of these elements in the studied rocks, requiring additional processes of fractional crystallization and/or hydrothermal injections.

En este trabajo se investiga la distribución de tierras raras (REE), elementos críticos de interés económico, en minerales accesorios de Pizarras Ordovícicas del Sinclinal de Truchas (Fm. Luarca, Zona Centro-Ibérica, León). Estas pizarras están formadas por cuarzo, moscovita y clorita (± albita) y minerales accesorios diversos: monacita (en parte sin-metamórfica), xenotima, allanita, zircón, apatito, óxidos (rutilo y magnetita) y sulfuros (pirita-pirrotina, calcopirita, galena, esfalerita y pentlandita). Se han realizado regresiones lineales múltiples entre la composición media de REE de las pizarras y de diferentes minerales accesorios de la literatura. Los resultados muestran que la combinación de monacita y xenotima, con abundancias modales de 0.046% y 0.013% respectivamente, explica satisfactoriamente los patrones de REE en roca total, de acuerdo con las observaciones de microscopia electrónica de barrido. Estos resultados permiten conocer el control mineralógico de la geoquímica de REE en estas pizarras Ordovícicas. Adicionalmente, la observación de monacita sin metamórfica es importante para futuros estudios geocronológicos.

Este artículo describe una propuesta docente para la formación superior de alumnos en técnicas de programación de robots manipuladores. El trabajo propone un conjunto de competencias que agrupan las capacidades necesarias para el aprendizaje de este tipo de metodologías. El desarrollo de la estrategia docente se basa en la configuración de un sistema que permite, desde un mismo terminal, testar un programa bien en simulación o, de forma alternativa, en un robot real colaborativo. El método propuesto permite compartir entre el alumnado, de forma racionalizada, el acceso a los robots del laboratorio, permitiendo que el programa probado en simulación presente una estructura idéntica al implantado en el robot real. La propuesta se desarrolla alrededor del programa MATLAB y el programa de simulación de robots RoboDK.

Polar skyrmions are particle-like objects consisted of swirling electric dipoles that hold promise for next generation nanodevices. Here, the authors explore the strain-induced transition from skyrmions to merons using electron imaging methods.

The Spanish Guideline on the Management of Asthma, better known by its acronym in Spanish GEMA, has been available for more than 20 years. Twenty-one scientific societies or related groups both from Spain and internationally have participated in the preparation and development of the updated edition of GEMA, which in fact has been currently positioned as the reference guide on asthma in the Spanish language worldwide.Its objective is to prevent and improve the clinical situation of people with asthma by increasing the knowledge of healthcare professionals involved in their care. Its purpose is to convert scientific evidence into simple and easy-to-follow practical recommendations. Therefore, it is not a monograph that brings together all the scientific knowledge about the disease, but rather a brief document with the essentials, designed to be applied quickly in routine clinical practice. The guidelines are necessarily multidisciplinary, developed to be useful and an indispensable tool for physicians of different specialties, as well as nurses and pharmacists.Probably the most outstanding aspects of the guide are the recommendations to: establish the diagnosis of asthma using a sequential algorithm based on objective diagnostic tests; the follow-up of patients, preferably based on the strategy of achieving and maintaining control of the disease; treatment according to the level of severity of asthma, using six steps from least to greatest need of pharmaceutical drugs, and the treatment algorithm for the indication of biologics in patients with severe uncontrolled asthma based on phenotypes. And now, in addition to that, there is a novelty for easy use and follow-up through a computer application based on the chatbot-type conversational artificial intelligence (ia-GEMA). Resumen: La Guía Española para el Manejo del Asma, mejor conocida por su acrónimo en español, GEMA, está a nuestra disposición desde hace más de veinte años. Veintiuna sociedades científicas o grupos relacionados, tanto de España como de otros países, han participado en la preparación y desarrollo de la edición actualizada de GEMA que, de hecho, se ha posicionado en la actualidad a nivel mundial como la guía de referencia sobre asma en lengua española.Su objetivo es prevenir y mejorar la situación clínica de las personas con asma, aumentando el conocimiento de los profesionales sanitarios involucrados en su cuidado. Su propósito es convertir la evidencia científica en recomendaciones prácticas sencillas y fáciles de seguir. Por lo tanto, no se trata de una monografía que reúna todo el conocimiento científico sobre la enfermedad, sino más bien de un documento conciso con lo esencial, diseñado para ser aplicado rápidamente en la práctica clínica de rutina. Las recomendaciones son necesariamente multidisciplinares, están desarrolladas para ser útiles y una herramienta indispensable para médicos de diferentes especialidades, así como para profesionales de enfermería y farmacia.Seguramente, los aspectos más destacados de la guía son las recomendaciones para: establecer el diagnóstico del asma utilizando un algoritmo secuencial basado en pruebas diagnósticas objetivas; el seguimiento de los pacientes, preferentemente basado en la estrategia de lograr y mantener el control de la enfermedad; el tratamiento según el nivel de gravedad del asma utilizando seis escalones, desde la menor hasta la mayor necesidad de medicamentos, y el algoritmo de tratamiento basado en fenotipos para la indicación de biológicos en pacientes con asma grave no controlada. A esto se suma ahora una novedad para su fácil uso y seguimiento a través de una aplicación informática basada en la inteligencia artificial conversacional de tipo chatbot (ia-GEMA).

Pig feeding prior to the extensive fattening phase might affect the final lipid profile and product quality. This study evaluates how maternal supplementation with vitamin E (VITE) (100 mg/kg), hydroxytyrosol (HXT) (1.5 mg/kg), or combined administration (VE + HXT) affects the piglet’s plasma and tissues’ fatty acid profiles and lipid stability according to the sow’s parity number (PN), as well as the possible changes to the lipid profile after extensive feeding. The sows’ PN affected the total fatty acid profile of plasma, muscle, and liver of piglets, with lower Δ-9 and Δ-6 desaturase indices but higher Δ-5 in those from primiparous (P) than multiparous (M) sows. Dietary VITE was more effective at decreasing C16:0 and saturated fatty acids in the muscle of piglets born from M than P sows, and modified the liver phospholipids in a different way. Sows’ supplementation with HXT increased C18:2n-6 in triglycerides and polyunsaturated fatty acids (PUFA) in muscle phospholipids. In the liver, HXT supplementation also increased free-PUFA and free-n-3 fatty acids. However, lipid oxidation of piglets’ tissues was not affected by the antioxidant supplementation, and it was higher in the livers of piglets born from M sows. The fatty acid profile in the muscle of pigs after extensive feeding was not affected by the PN, but it was by the sows’ antioxidant supplementation, with positive effects on quality by both compounds.

La Sentencia Bank M. del TJUE declara incompatible con la Directiva 93/13 cualquier pretensión del prestamista que ha empleado una cláusula abusiva que hace nulo el contrato que vaya más allá de la pura restitución del importe nominal del capital prestado (y, en su caso, del interés moratorio sobre ese importe nominal computado desde la reclamación efectuada al consumidor). La Sentencia comentada pone fin a una situación de incertidumbre sobre los préstamos en divisas que han caracterizado distintos mercados de crédito en Europa central y oriental. Con su decisión, sin embargo, el TJUE hace un mal servicio a una adecuada y actualizada comprensión de la ordenación de los efectos de la ineficacia de los contratos puramente financieros y empaña la búsqueda de soluciones coherentes que conjuguen la disuasión del empleo de cláusulas abusivas y la debida compensación a los consumidores afectados con el correcto funcionamiento de la restitución post-nulidad en contratos cuyas prestaciones son flujos financieros.

En el presente artículo se realiza una revisión sistemática de la literatura internacional sobre los factores que impulsan una diversificación económica exitosa que pueden ser objeto de políticas públicas y de estrategias industriales regionales. Mediante la identificación, la evaluación y la integración de los estudios empíricos más relevantes y de alta calidad en el tema, fueron identificados los mecanismos más determinantes para alcanzar una diversificación productiva que impulse el crecimiento económico de los países y regiones. Los principales resultados son discutidos considerando las características para su implementación regional en México.

Taurine, a cysteine-derived zwitterionic sulfonic acid, is a common ingredient in energy drinks and is naturally found in fish and other seafood. In humans, taurine is produced mainly in the liver, and it can also be obtained from food. In target tissues, such as the retina, heart, and skeletal muscle, it functions as an essential antioxidant, osmolyte, and antiapoptotic agent. Taurine is also involved in energy metabolism and calcium homeostasis. Taurine plays a considerable role in bone growth and development, and high-profile reports have demonstrated the importance of its metabolism for bone health. However, these reports have not been collated for more than 10 years. Therefore, this review focuses on taurine–bone interactions and covers recently discovered aspects of taurine’s effects on osteoblastogenesis, osteoclastogenesis, bone structure, and bone pathologies (e.g., osteoporosis and fracture healing), with due attention to the taurine–cartilage relationship.

Background: Hypertension awareness and control are understudied among older adults in middle-income countries, with limited work contextualizing awareness and control across layers of influence (individual to the community). Research on hypertension in Latin America is acknowledged as insufficient. Objectives: This study applies the socioecological model (SEM) to examine individual, interpersonal, institutional, and community factors related to hypertension awareness and control in older adults residing in Brazil and Colombia. It identifies groups of older adults more likely to be unaware of their condition and/or to have challenges achieving hypertension control. Methods: We analyzed International Mobility in Aging Study data of 803 community-dwelling adults 65–74 years from study sites in the two most populous countries in South America. The study framework was the socioecological model. Logistic regression models identified factors associated with hypertension awareness and control. Conclusions: Hypertension was prevalent in both samples (>70%), and awareness was high (>80%). Blood pressure control among diagnosed respondents was low: 30% in Brazil and 51% in Colombia. Factors across the socioecological model were associated with awareness and control, with notable differences across countries. Those with diabetes (OR 4.19, 95%CI 1.64–10.71) and insufficient incomes (OR: 1.85, 95%CI 1.03–3.31) were more likely to be aware of their hypertension. In Colombia, those reporting no community activity engagement were less likely to be aware compared to those reporting community activities. In Brazil, it was the opposite. Women (OR 1.66, 95%CI 1.12–2.46) and those reporting strolling shops and stores (OR 1.80, 95% CI 1.09–3.00) were significantly more likely to have their hypertension under control. In Brazil, those 70–75 were significantly less likely to have their hypertension under control compared to their younger counterparts. In Colombia, this was not observed. This paper highlights the importance of theory-based studies within unique Latin American contexts on hypertension and suggests novel opportunities for intervention.

This article introduces a control architecture designed for the development of Hybrid Remotely Operated Underwater Vehicles. The term ”Hybrid” characterizes Remotely Operated systems capable of autonomously executing specific operations. The presented architecture maintains teleoperation capabilities while enabling two fully autonomous applications. The approach emphasizes the implementation of reactive navigation by exclusively utilizing data from a Mechanical Scanned Imaging Sonar for control decisions. This mandates the control system to solely react to data derived from the vehicle’s environment, without considering other positioning information or state estimation. The study involves transforming a small-scale commercial Remotely Operated Underwater Vehicle into a hybrid system without structural modifications, and details the development of an intermediate Operational Control Layer responsible for sensor data processing and task execution control. Two practical applications, inspired by tasks common in natural or open-water aquaculture farms, are explored: one for conducting transects, facilitating monitoring and maintenance operations, and another for navigating toward an object for inspection purposes. Experimental results validate the feasibility and effectiveness of the authors’ hypotheses. This approach expands the potential applications of underwater vehicles and facilitates the development of Hybrid Remotely Operated Underwater Vehicles, enabling the execution of autonomous reactive tasks.

Abstract Background Driver mutations are the genetic components responsible for tumor initiation and progression. These variants, which may be inherited, influence cancer risk and therefore underlie many familial cancers. The present study examines the potential association between SNPs in driver genes SF3B1 (rs4685), TBX3 (rs12366395, rs8853, and rs1061651) and MAP3K1 (rs72758040) and BC in BRCA1/2-negative Chilean families. Methods The SNPs were genotyped in 486 BC cases and 1258 controls by TaqMan Assay. Results Our data do not support an association between rs4685:C > T, rs8853:T > C, or rs1061651:T > C and BC risk. However, the rs12366395-G allele (A/G + G/G) was associated with risk in families with a strong history of BC (OR = 1.2 [95% CI 1.0–1.6] p = 0.02 and OR = 1.5 [95% CI 1.0–2.2] p = 0.02, respectively). Moreover, rs72758040-C was associated with increased risk in cases with a moderate-to-strong family history of BC (OR = 1.3 [95% CI 1.0–1.7] p = 0.02 and OR = 1.3 [95% CI 1.0–1.8] p = 0.03 respectively). Finally, risk was significantly higher in homozygous C/C cases from families with a moderate-to-strong BC history (OR = 1.8 [95% CI 1.0–3.1] p = 0.03 and OR = 1.9 [95% CI 1.1–3.4] p = 0.01, respectively). We also evaluated the combined impact of rs12366395-G and rs72758040-C. Familial BC risk increased in a dose-dependent manner with risk allele count, reflecting an additive effect (p-trend = 0.0002). Conclusions Our study suggests that germline variants in driver genes TBX3 (rs12366395) and MAP3K1 (rs72758040) may influence BC risk in BRCA1/2-negative Chilean families. Moreover, the presence of rs12366395-G and rs72758040-C could increase BC risk in a Chilean population.

The polar chiral texture of the vortex or skyrmion structure in ferroelectric oxide PbTiO3/SrTiO3 superlattice attracts attention. Here, the authors report a theoretical framework to probe emergent chirality of electrical polarization textures.

Las características económicas de los contratos de crédito y, señaladamente, su naturaleza de intercambio puramente financiero, así como la importancia del elemento de la “selección” del deudor, desempeñan un papel muy destacado para iluminar -y, en buena medida, simplificar- los problemas de Derecho de contratos a los que se enfrentan los contratos de financiación con consumidores. En particular, las cuestiones de ineficacia y restitución, así como el modo de completar el contrato tras la declaración de abusividad de una cláusula, se traducen generalmente en un problema de determinación de quién ha de pagar y cuánto. Con esta perspectiva, tratamos de explicar algunas cuestiones relativas a la contratación de préstamos en divisa, todavía pendientes de solución por el TJUE en cuanto a ciertos aspectos de la aplicación de la Directiva 93/13.

La información sobre sostenibilidad y su credibilidad son objeto de un interés internacional creciente. La actual Directiva 2014/95/UE de información no financiera va a ser sustituida por la Directiva de información corporativa en materia de sostenibilidad con el objetivo de mejorar la comparabilidad, relevancia y credibilidad de la información no financiera reportada en el entorno europeo. En el presente artículo analizamos ambas Directivas, otras iniciativas internacionales en materia de información sobre sostenibilidad, así como la situación presente y futura de la verificación de dicha información. Además, proponemos un informe de auditoría novedoso para la información no financiera basado en una encuesta a auditores y usuarios en España. Nuestra propuesta puede mejorar la comunicación entre auditores y usuarios y favorecer la confianza de los grupos de interés en la información sobre sostenibilidad reportada. Recibido: 30 abril 2022 Aceptado: 30 mayo 2022

Education is a concept that encompasses not only the teaching-learning process but also the conditions, environment, and facilities in which it takes place. Education is a precondition to development because it serves as a society’s primary engine of innovation. Therefore, the concept of a space designated as an Innovation District is essential for the creation of Sustainable Cities since it is in such spaces that jobs are created and new markets specializing in products and high-added value services emerge. However, in the past, successful innovation districts have generally been found in developed countries, which have sufficient resources to invest in projects of this magnitude. Our methodology consists of a case study, the city of Querétaro, in central Mexico, to analyze the role of higher education within developing countries that seek to create innovation districts. We employ quantitative methods such as Geographic Information Systems (GIS) and locations quotients, along with qualitative documentary analysis, to conduct a spatial-urban analysis, characterize the industrial configuration, and to analyze the design of educational models adapted to the needs of specific industries. The results of our case study suggest that cities from developing countries that are fast industrializing can best maximize their chances of success by encouraging an explicit collaboration between industry and education through a Triple Helix Model. Such a collaboration would be based on matching educational competencies with opportunities for industrial reconfiguration to carefully select the location for the new district and decide over its area of specialization.

La minería ha tenido una gran influencia en las sociedades humanas, permeando por igual las riquezas del suelo y la cultura, lo que ha tenido profundas implicaciones para los individuos dedicados a esta labor y para los lugares en los que se lleva a cabo. En el presente artículo, se describen las características socioculturales y de sanidad, así como las enfermedades más frecuentes en las minas de oro de Marmato (Caldas) durante el siglo XIX. Las precarias condiciones de salubridad y las enfermedades tropicales infecciosas persistieron en la población durante todo el siglo.

Objective. To identify the main factors associated with disability in older adults in Colombia, adjusted according to structural and intermediary determinants of healthy aging. Methods. This study used cross-sectional data from 23 694 adults over 60 years of age in the SABE Colombia nationwide survey. Structural determinants such as demographic and socioeconomic position variables were analyzed. Intermediary variables were classified into three blocks: intrinsic capacity, physical and built environment, and health care systems. Data analysis employed multivariate logistic regression. Results. The prevalence of overall disability was 21% for activities of daily living, 38% for instrumental activities of daily living, and 33% for mobility disability. Disability was associated with sociodemographic structural determinants such as older age, female sex, rural residence, never married/divorced, living alone, low educational level, and Indigenous/Black ethnicity. With regard to determinants of socioeconomic position, net low income, poor socioeconomic stratum, insufficient income perception, and a subsidized health insurance scheme exerted a major influence on disability. Intermediary determinants of intrinsic capacity, such as poor self-rated health, multimorbidity, low grip strength, sedentary lifestyle, early childhood economic adversity, no social support, and no participation in activities, were significantly associated with disability. Conclusions. Actions that affect the main factors associated with disability, such as reducing health inequities through policies, strategies, and activities, can contribute significantly to the well-being and quality of life of Colombian older adults.

Performance-based seismic codes ensure proper inelastic behaviour of reinforced concrete frames through capacity design, among others. This strategy relies not only on avoiding brittle failures and providing ductility to plastic hinges but also in their distribution within the frame aimed at a greater number of storeys involved in the eventual collapse mechanism. Although codes are generally in agreement to some basic principles in order to ensure capacity design, they show some discrepancies regarding the specific strategies. In this paper, capacity design provisions proposed by some European current codes—Eurocode 8, Italian NTC, and Spanish NCSE-02—are compared, and their effectiveness is discussed. The alternative formulation proposed by Italian code for “strong column–weak beam” turns out to be not suitable under specific circumstances, such as with large gravity loads or significant cantilever deformation in lower storeys. Regarding the value of axial load in columns to be considered for the calculation of shear and moment capacities, provisions in the three codes could eventually cause unconservative design for perimeter columns. The Spanish whole set of provisions is proved to not be effective due to their different fundamentals—they are based on overstrength instead of capacity. For all the three cases, some alternative procedures are suggested in this work.

Eye blink artifacts in electroencephalographic (EEG) signals have been used in multiple applications as an effective method for human–computer interaction. Hence, an effective and low-cost blinking detection method would be an invaluable aid for the development of this technology. A configurable hardware algorithm, described using hardware description language, for eye blink detection based on EEG signals from a one-channel brain–computer interface (BCI) headset was developed and implemented, showing better performance in terms of effectiveness and detection time than manufacturer-provided software.

Abstract RNA hybridization‐based spatial transcriptomics provides unparalleled detection sensitivity. However, inaccuracies in segmentation of image volumes into cells cause misassignment of mRNAs which is a major source of errors. Here, we develop JSTA, a computational framework for joint cell segmentation and cell type annotation that utilizes prior knowledge of cell type‐specific gene expression. Simulation results show that leveraging existing cell type taxonomy increases RNA assignment accuracy by more than 45%. Using JSTA, we were able to classify cells in the mouse hippocampus into 133 (sub)types revealing the spatial organization of CA1, CA3, and Sst neuron subtypes. Analysis of within cell subtype spatial differential gene expression of 80 candidate genes identified 63 with statistically significant spatial differential gene expression across 61 (sub)types. Overall, our work demonstrates that known cell type expression patterns can be leveraged to improve the accuracy of RNA hybridization‐based spatial transcriptomics while providing highly granular cell (sub)type information. The large number of newly discovered spatial gene expression patterns substantiates the need for accurate spatial transcriptomic measurements that can provide information beyond cell (sub)type labels.

Introduction: Potentially inappropriate medication is associated with adverse health and functional outcomes, as well as increased health care costs. Objective: To estimate the prevalence and types of potentially inappropriate medication according to the Beers criteria in community-dwelling older persons and to identify the major clinical and functional consequences of potentially inappropriate medication during two years of following. Materials and methods: We conducted a longitudinal, descriptive, and observational study that included 400 65-year or older community-dwelling people (48% women) selected by simple random sampling in 2012. In 2014, 372 people were re-evaluated and classified into two groups based on the presence or absence of potentially inappropriate medication through the follow-up period. Results: In total, 31% had polypharmacy (5-9 medications) and 1,8% had excessive polypharmacy (10 or more medications). The mean of the number of medications was higher in the potentially inappropriate medication group (3 vs. 5.78; p

The human colonic mucus is mainly composed of mucins, which are highly glycosylated proteins. The normal commensal colonic microbiota has mucolytic activity and is capable of releasing the monosaccharides contained in mucins, which can then be used as carbon sources by pathogens such as Enterohemorrhagic Escherichia coli (EHEC). EHEC can regulate the expression of some of its virulence factors through environmental sensing of mucus-derived sugars, but its implications regarding its main virulence factor, Shiga toxin type 2 (Stx2), among others, remain unknown. In the present work, we have studied the effects of five of the most abundant mucolytic activity-derived sugars, Fucose (L-Fucose), Galactose (D-Galactose), N-Gal (N-acetyl-galactosamine), NANA (N-Acetyl-Neuraminic Acid) and NAG (N-Acetyl-D-Glucosamine) on EHEC growth, adhesion to epithelial colonic cells (HCT-8), and Stx2 production and translocation across a polarized HCT-8 monolayer. We found that bacterial growth was maximum when using NAG and NANA compared to Galactose, Fucose or N-Gal, and that EHEC adhesion was inhibited regardless of the metabolite used. On the other hand, Stx2 production was enhanced when using NAG and inhibited with the rest of the metabolites, whilst Stx2 translocation was only enhanced when using NANA, and this increase occurred only through the transcellular route. Overall, this study provides insights on the influence of the commensal microbiota on the pathogenicity of E. coli O157:H7, helping to identify favorable intestinal environments for the development of severe disease.

Introducción: la falta de adherencia implica peor control de la diabetes y aumento del número de complicaciones, lo que a menudo se traduce en un mayor gasto sanitario. Las hipoglucemias, en ocasiones inadvertidas, son una de las principales consecuencias de la no adherencia y su prevención pasa por intervenciones multidisciplinares que ayuden a la mejora de la adherencia. Objetivos: medir la adherencia a hipoglucemiantes, detectar y cuantificar hipoglucemias inadvertidas y recurrentes, conocer la percepción de los pacientes sobre su tratamiento y derivar al médico en casos de no adherencia e hipoglucemias no solucionadas. Material y métodos: estudio observacional, transversal y multicéntrico, en farmacias comunitarias, realizado a partir de abril de 2019 con diabéticos tipo 2 en tratamiento con hipoglucemiantes que lleven ≥12 meses con la misma pauta. Para la detección de hipoglucemias, los que estén en tratamiento con sulfonilureas, glinidas y/o insulinas. Diseño de un cuestionario con datos sociodemográficos, enfermedades y tratamientos. Utilización del test MMAS-8 para detectar no adherencia y del test de Clarke para hipoglucemias. Si se detecta incumplimiento y/o hipoglucemia y no se puede solucionar por el farmacéutico se derivará al médico de familia. Análisis estadístico: se utilizará el programa STATA13 para Windows®. Se realizarán análisis bivariados y multivariados. La significación se fijará en p

Introducción. El fenotipo de envejecimiento saludable está presente en aquellos individuos que envejecen con poca morbilidad, sin deterioro funcional ni cognitivo, y con un nivel aceptable de bienestar y de participación social. Objetivo. Establecer la frecuencia del fenotipo de envejecimiento saludable según un modelo multidimensional, uno biomédico y uno psicosocial, y determinar los factores de predicción en cada uno de ellos. Materiales y métodos. Se hizo un estudio de diseño transversal, observacional y descriptivo, que incluyó a 402 personas (50,1 % mujeres) de 65 años y más (promedio de edad, 69,2) en el área urbana de Manizales. El fenotipo de envejecimiento saludable se caracterizó en cinco dimensiones: salud metabólica y fisiológica, función física, función cognitiva, bienestar psicológico y bienestar social. Los factores asociados incluyeron aspectos sociodemográficos y de salud. Resultados. La prevalencia de envejecimiento saludable fue de 15,5 % en el modelo multidimensional, de 12,3 % en el biomédico y de 63,3 % en el psicosocial. El tener autopercepción de buena salud fue un factor de predicción independiente de envejecimiento saludable en los tres modelos, así como la satisfacción con los ingresos económicos en el modelo biomédico y en el psicosocial. Un tercer factor de predicción fue el estar casado, aunque fue significativo solamente en el modelo psicosocial. Conclusiones. La prevalencia del fenotipo de envejecimiento saludable fue baja en el modelo biológico y en el multidimensional (1 de cada 10 personas), y mayor en el modelo psicosocial (6 de cada 10). A pesar de ello, los factores predictores independientes fueron los mismos: la autopercepción de buena o muy buena salud, la satisfacción con los ingresos económicos y el estar casado.

Reseña de: Fernando de Pulgar, Claros varones de Castilla. Letras. Edición, estudios y notas de María Isabel de Páiz Hernández y Pedro Martín Baños con Gonzalo Pontón Gijón. Madrid: R.A.E., 2022, 592 pp. ISBN: 978-84-670-6554-1.

Sedimentary rocks are our window to understand the history and evolution of the surface of our planet. The sedimentary record, although biased by variable preservation conditions and post depositional processes, potentially preserve signals of the interaction between physical, chemical and biological processes that takes place at the interface between the Geosphere, the Hydrosphere/ Atmosphere and the Lithosphere. Geochemistry, integrated with Sedimentology, has become a standard approach to unravel these interactions and to provide some insights for the understanding of how sedimentary geochemistry is preserved within different sedimentary environments. Microbial life is ubiquitous at the Earth’s surface (Whitman et al., 1998), and has been present throughout our Planet’s history. It has evolved to exploit the energy provided by gradients in geochemical composition between rocks, organic materials and surface fluids, using this energy for maintenance and growth (Hoeler, 2007). Due to their abundance, chemical reactivity and metabolic activity (Konhauser, 2007), microbes play a central role in biogeochemical cycles (C, O, N, S, Fe, etc) at both, micro and macroscopic scales (Schlesinger and Bernhardt, 2020). The best example of these processes are the current chemical composition of our O2-rich atmosphere or the chemical redox gradients that exist at the sediment-water interface in most sedimentary environments around the world, where early diagenesis driven by organic matter degradation takes place (Aller, 2014). In addition, microbial mats and biofilms influence the precipitation/dissolution of minerals such as carbonates (explaining the the abundance of microbialites in the ancient rock record, Riding, 2011) as well as the rheological and mechanical behaviour of detrital sediments, where a classic example are known as MISS (Microbially induced sedimentary structures, Noffke et al., 2010). For these reasons, whenever we talk about sedimentary geochemistry we are actually talking about sedimentary biogeochemistry and geomicrobiology. This is so since microbial activity has been shaping the surface chemistry and composition of our planet, as previously recognized by the pioneering work of Vladimir Vernadsky in 1926 and later by Lourens Baas-Becking in 1934 (Knoll et al., 2012). Vernadsky and Baas-Becking early ideas have grown and become the lens through which we scientifically observe our world, making it clear that the Biosphere adds another layer of diversity and complexity in order to understand our planet as a system.

Se presenta un caso inusitado de hemorragia peritoneal espontánea originada por una apoplejía adrenal izquierda, tratado en el Hospital Universitario San Vicente de Paúl de Medellín. Se revisa la literatura disponible sobre el tema y se hace énfasis en los factores epidemiológicos, fisiopatológicos, manifestaciones clínicas e imágenes diagnósticas de esta rara entidad.

Se presenta el caso de 1 paciente con un cuerpo extraño -aguja de coser- en el pericardio, introducido de manera accidental al tórax, 6 meses antes de la consulta. El caso fue resuelto con éxito mediante toracoscopia videoasistida. El diagnóstico se logró con la radiografía simple del tórax y el estudio fluoroscópico.

Resumen: El asma es una de las enfermedades crónicas más prevalentes en España. La Sociedad Española de Alergología e Inmunología Clínica (SEAIC), la Sociedad Española de Médicos de Atención Primaria (SEMERGEN), la Sociedad Española de Medicina Familiar y Comunitaria (semFYC), la Sociedad Española de Médicos Generales y de Familia (SEMG) y la Sociedad Española de Neumología y Cirugía Torácica (SEPAR) consensuaron en 2019 un documento donde se establecieron criterios de derivación y pautas de actuación en el diagnóstico, control y seguimiento del paciente asmático con el fin de facilitar la continuidad asistencial y una mejor atención en cada ámbito. Las nuevas circunstancias motivadas por la pandemia covid-19 y nuevas evidencias científicas en algunos aspectos han llevado a actualizar algunas de las recomendaciones de la anterior edición, adaptándolas a la nueva situación asistencial. Abstract: Asthma is one of the most prevalent chronic diseases in Spain. In 2019, the Spanish Society of Allergology and Clinical Immunology (SEAIC), the Spanish Society of Primary Care Physicians (SEMERGEN), the Spanish Society of Family and Community Medicine (semFYC), the Spanish Society of General and Family Physicians (SEMG) and the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) drafted a document laying down the criteria for referral and action guidelines in the diagnosis, control and monitoring of the asthmatic patient to facilitate ongoing care and improved attention in every setting. The new circumstances derived from the Covid-19 pandemic have demanded that some of the recommendations of the previous edition be updated and adapted to the new healthcare situation.

Background: The basilic vein is a deep vein which usually requires superficialisation and surgical transposition. Material and methods: This is a retrospective study of 119 BBAVF-ST in patients with stage 5D chronic kidney disease who received an implant with a one-stage surgical technique (2011–2015). The percentage of primary (PP), assisted primary (APP) and secondary (SP) permeabilities were assessed, as well as the related complications. We analyzed the permeabilities using Kaplan–Meier survival curves and a univariate Log Rank analysis (Mantel–Cox). p values less than or equal to 0.05 were considered as significant. Results: The mean age of the study group was 67.9 years, with 63.8% of the subjects being male. A total of 57 complications were detected during the follow-up period: 24 stenosis (42.1%), 11 thrombosis (19.2%), 7 vascular access steal syndromes (12.2%), 7 upper limb oedemas (12.2%), 6 post-puncture haematomas (10.5%) and 2 infections (3.5%). The percentages of PP obtained at 1, 6, 12 and 24 months were 92.4%, 79.8%, 66.3% and 52%; APP: 94.1%, 87.3%, 80.4% and 65.6%, and SP: 95%, 89.1%, 84% and 67.5%, respectively. Diabetic patients presented with significantly worse permeabilities than vascular or idiopathic patients: (p = .037, .009 and .019, respectively). Conclusions: According to the results obtained in our study, the one-stage surgical implementation of BBAVF-ST presents high permeability rates and a small number of related complications. Diabetes mellitus is a factor related to a worse surgical prognosis. Some of the biggest advantages are the greater optimization of health resources and a shorter time in which the central venous catheter needs to remain in the body. Resumen: Introducción: La vena basílica se caracteriza por ser un vaso profundo que en la mayoría de los casos requiere superficialización y trasposición quirúrgica. Material y métodos: Estudio retrospectivo de 119 FAVn HB S-T en pacientes con insuficiencia renal crónica 5D implantadas en un solo acto quirúrgico (2011-2015). Se analiza el porcentaje de permeabilidades primaria (PP), primaria asistida (PPA) y secundaria (PS), así como las complicaciones asociadas. Análisis de permeabilidades mediante curvas de supervivencia Kaplan-Meier y análisis univariante mediante Log Rank (Mantel-Cox). Se considera significativa una p ≤ 0,05. Resultados: Edad media 67,9 años y 63,8% hombres. Durante el período de seguimiento se objetivaron un total de 57 complicaciones: 24 estenosis (42,1%), 11 trombosis (19,2%), 7 síndromes de robo vascular (12,2%), 7 edemas de extremidad superior (12,2%), 6 hematomas pospunción (10,5%) y 2 infecciones (3,5%). Los porcentajes de PP obtenidos a 1, 6, 12 y 24 meses: 92,4, 79,8, 66,3 y 52; PPA: 94,1, 87,3, 80,4 y 65,6%, y PS: 95, 89,1, 84 y 67,5%. Se constataron diferencias significativas en las curvas de PP, PPA y PS según la etiología, presentando peores permeabilidades los diabéticos respecto a la vascular e idiopática (p = 0,037, 0,009 y 0,019). Conclusiones: La implantación quirúrgica de FAVn HB S-T en un solo acto ofrece buenas tasas de permeabilidad y escaso número de complicaciones asociadas. La diabetes mellitus representa un factor de peor pronóstico quirúrgico. Entre las mayores ventajas destacan una mejor optimización de los recursos sanitarios y menor tiempo de permanencia del catéter venoso central. Keywords: Haemodialysis, Vascular access, Basilic-humeral arteriovenous fistula, Single-stage surgical technique, Palabras clave: Hemodiálisis, Acceso vascular, Fístula arteriovenosa nativa humerobasílica, Un solo acto quirúrgico

Resumen: Introducción: La vena basílica se caracteriza por ser un vaso profundo que en la mayoría de los casos requiere superficialización y trasposición quirúrgica. Material y métodos: Estudio retrospectivo de 119 FAVn HB S-T en pacientes con insuficiencia renal crónica 5D implantadas en un solo acto quirúrgico (2011-2015). Se analiza el porcentaje de permeabilidades primaria (PP), primaria asistida (PPA) y secundaria (PS), así como las complicaciones asociadas. Análisis de permeabilidades mediante curvas de supervivencia Kaplan-Meier y análisis univariante mediante Log Rank (Mantel-Cox). Se considera significativa una p ≤ 0,05. Resultados: Edad media 67,9 años y 63,8% hombres. Durante el período de seguimiento se objetivaron un total de 57 complicaciones: 24 estenosis (42,1%), 11 trombosis (19,2%), 7 síndromes de robo vascular (12,2%), 7 edemas de extremidad superior (12,2%), 6 hematomas pospunción (10,5%) y 2 infecciones (3,5%). Los porcentajes de PP obtenidos a 1, 6, 12 y 24 meses: 92,4, 79,8, 66,3 y 52; PPA: 94,1, 87,3, 80,4 y 65,6%, y PS: 95, 89,1, 84 y 67,5%. Se constataron diferencias significativas en las curvas de PP, PPA y PS según la etiología, presentando peores permeabilidades los diabéticos respecto a la vascular e idiopática (p = 0,037, 0,009 y 0,019). Conclusiones: La implantación quirúrgica de FAVn HB S-T en un solo acto ofrece buenas tasas de permeabilidad y escaso número de complicaciones asociadas. La diabetes mellitus representa un factor de peor pronóstico quirúrgico. Entre las mayores ventajas destacan una mejor optimización de los recursos sanitarios y menor tiempo de permanencia del catéter venoso central. Abstract: Background: The basilic vein is a deep vein which usually requires superficialisation and surgical transposition. Material and methods: This is a retrospective study of 119 BBAVF-ST in patients with stage 5D chronic kidney disease who received an implant with a one-stage surgical technique (2011-2015). The percentage of primary (PP), assisted primary (APP) and secondary (SP) permeabilities were assessed, as well as the related complications. We analysed the permeabilities using Kaplan-Meier survival curves and a univariate Log Rank analysis (Mantel-Cox). P values less than or equal to 0.05 were considered as significant. Results: The mean age of the study group was 67.9 years, with 63.8% of the subjects being male. A total of 57 complications were detected during the follow-up period: 24 stenosis (42.1%), 11 thrombosis (19.2%), 7 vascular access steal syndromes (12.2%), 7 upper limb oedemas (12.2%), 6 post-puncture haematomas (10.5%) and 2 infections (3.5%). The percentages of PP obtained at 1, 6, 12 and 24 months were 92.4%, 79.8%, 66.3% and 52%; APP: 94.1%, 87.3%, 80.4% and 65.6%, and SP: 95%, 89.1%, 84% and 67.5%, respectively. Diabetic patients presented with significantly worse permeabilities than vascular or idiopathic patients: (P = .037, .009 and .019, respectively). Conclusions: According to the results obtained in our study, the one-stage surgical implementation of BBAVF-ST presents high permeability rates and a small number of related complications. Diabetes mellitus is a factor related to a worse surgical prognosis. Some of the biggest advantages are the greater optimisation of health resources and a shorter time in which the central venous catheter needs to remain in the body. Palabras clave: Hemodiálisis, Acceso vascular, Fístula arteriovenosa nativa humerobasílica, Un solo acto quirúrgico, Keywords: Haemodialysis, Vascular access, Basilic-humeral arteriovenous fistula, Single-stage surgical technique