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Abstract Background Tissue stiffness, dictated by organisation of interstitial fibrillar collagens, increases breast cancer risk and contributes to cancer progression. Tamoxifen is a standard treatment for receptor-positive breast cancer and is also aproved for primary prevention. We investigated the effect of tamoxifen and its main metabolites on the breast tissue collagen organisation as a proxy for stiffness and explored the relationship between mammographic density (MD) and collagen organisation. Material and methods This sub-study of the double-blinded dose-determination trial, KARISMA, included 83 healthy women randomised to 6 months of 20, 10, 5, 2.5, and 1 mg of tamoxifen or placebo. Ultrasound-guided core-needle breast biopsies collected before and after treatment were evaluated for collagen organisation by polarised light microscopy. Results Tamoxifen reduced the amount of organised collagen and overall organisation, reflected by a shift from heavily crosslinked thick fibres to thinner, less crosslinked fibres. Collagen remodelling correlated with plasma concentrations of tamoxifen metabolites. MD change was not associated with changes in amount of organised collagen but was correlated with less crosslinking in premenopausal women. Conclusions In this study of healthy women, tamoxifen decreased the overall organisation of fibrillar collagens, and consequently, the breast tissue stiffness. These stromal alterations may play a role in the well-established preventive and therapeutic effects of tamoxifen. Trial registration ClinicalTrials.gov ID: NCT03346200. Registered November 1st, 2017. Retrospectively registered.

Abstract Intervalley excitons with electron and hole wavefunctions residing in different valleys determine the long-range transport and dynamics observed in many semiconductors. However, these excitons with vanishing oscillator strength do not directly couple to light and, hence, remain largely unstudied. Here, we develop a simple nanomechanical technique to control the energy hierarchy of valleys via their contrasting response to mechanical strain. We use our technique to discover previously inaccessible intervalley excitons associated with K, Γ, or Q valleys in prototypical 2D semiconductors WSe2 and WS2. We also demonstrate a new brightening mechanism, rendering an otherwise “dark” intervalley exciton visible via strain-controlled hybridization with an intravalley exciton. Moreover, we classify various localized excitons from their distinct strain response and achieve large tuning of their energy. Overall, our valley engineering approach establishes a new way to identify intervalley excitons and control their interactions in a diverse class of 2D systems.

The experiments allowed by current machine learning models imply a revival of the debate on the causes of specific trends of human visual psychophysics. Machine learning facilitates the exploration of the effect of specific visual goals (such as image segmentation) by different neural architectures in different statistical environments in an unprecedented manner. In this way, (1) the principles behind psychophysical facts such as the non-Euclidean nature of human color discrimination and (2) the emergence of human-like behaviour in artificial systems can be explored under a new light. In this work, we show for the first time that the tolerance or invariance of image segmentation networks for natural images under changes of illuminant in the color space (a sort of insensitivity region around the white) is an ellipsoid oriented similarly to a (human) MacAdam ellipse. This striking similarity between an artificial system and human vision motivates a set of experiments checking the relevance of the statistical environment on the emergence of such insensitivity regions. Results suggest, that in this case, the statistics of the environment may be more relevant than the architecture selected to perform the image segmentation.

DNA knots are deleterious for living cells if not removed. Several theoretical and simulation approaches address the question of how topoisomerases select the intermolecular passages that preferentially lead to unknotting rather than to the knotting of randomly fluctuating DNA molecules, but the formation of knots in vivo remains poorly understood. DNA knots form in vivo in non-replicating and replicating molecules, and supercoiling as well as intertwining are thought to play a crucial role in both the formation and resolution of DNA knots by topoisomerase IV. To confirm this idea, we used two-dimensional agarose gel electrophoresis run with different concentrations of chloroquine to demonstrate that non-replicating pBR322 plasmids grown in a topoisomerase I-defective E. coli strain (RS2λ) were more negatively supercoiled than in a wild-type strain (W3110) and, concurrently, showed significantly fewer knots. In this way, using wild-type and E. coli mutant strains, we confirmed that one of the biological functions of DNA supercoiling is to reduce the formation of DNA knots.

Abstract Background The expressions of a “wish to hasten death” or “wish to die” raise ethical concerns and challenges. These expressions are related to ethical principles intertwined within the field of medical ethics, particularly in end-of-life care. Although some reviews were conducted about this topic, none of them provides an in-depth analysis of the meanings behind the “wish to hasten death/die” based specifically on the ethical principles of autonomy, dignity, and vulnerability. The aim of this review is to understand if and how the meanings behind the “wish to hasten death/die” relate to and are interpreted in light of ethical principles in palliative care. Methods We conducted a meta-ethnographic review according to the PRISMA guidelines and aligned with Noblit and Hare’s framework. Searches were performed in three databases, Web of Science, PubMed, CINAHL, with no time restrictions. Original qualitative studies exploring the meanings given by patients, family caregivers and healthcare professionals in any context of palliative and end-of-life care were included. A narrative synthesis was undertaken. PROSPERO registration CRD42023360330. Results Out of 893 retrieved articles, 26 were included in the analysis, accounting for the meanings of a total of 2,398 participants. Several factors and meanings associated with the “wish to hasten death” and/or “wish to die” were identified and are mainly of a psychosocial and spiritual nature. The ethical principles of autonomy and dignity were the ones mostly associated with the “wish to hasten death”. Ethical principles were essentially inferred from the content of included articles, although not explicitly stated as bioethical principles. Conclusions This meta-ethnographic review shows a reduced number of qualitative studies on the “wish to hasten death” and/or “wish to die” explicitly stating ethical principles. This suggests a lack of bioethical reflection and reasoning in the empirical end-of-life literature and a lack of embedded ethics in clinical practice. There is a need for healthcare professionals to address these topics compassionately and ethically, taking into account the unique perspectives of patients and family members. More qualitative studies on the meanings behind a wish to hasten death, their ethical contours, ethical reasoning, and implications for clinical practice are needed.

During the last third of the eighteenth century Spanish ministers showed a growing interest in establishing permanent peaceful relations with Muslim states in the Maghreb and the eastern Mediterranean, such as the Ottoman and Alawite empires; as well as with all kinds of Amerindian peoples in the Mississippi Valley, such as the Creeks, Talapuches or Tunicas. How can we explain this coincidence? How can we analyse this growing Hispanic interest in Turks, Moors, and barbarian Indians? Based on the use of global microhistory, this article argues for the need to analyse jointly Hispanic diplomacy and diplomatic practices vis-à-vis non-Christian and independent states in various parts of the Mediterranean and the enlightened Atlantic, seeking to understand the implications of globalisation for Hispanic imperial policy and its growing weight for the Bourbons. In line with this, the article explains the active Carolinian representation and convergences in the practices of transcultural diplomacy, highlighting the global interdependence between regional conflicts in the development of the Hispanic policy of Charles III.

Two-dimensional (2D) agarose gel electrophoresis is the method of choice to analyze DNA topology. The possibility to use E. coli strains with different genetic backgrounds in combination with nicking enzymes and different concentrations of norfloxacin improves the resolution of 2D gels to study the electrophoretic behavior of three different families of DNA topoisomers: supercoiled DNA molecules, post-replicative catenanes, and knotted DNA molecules. Here, we describe the materials and procedures required to optimize their separation by 2D gels. Understanding the differences in their electrophoretic behavior can help explain some important physical characteristics of these different types of DNA topoisomers.

A continuación se realiza una recensión sobre el libro Instrumentos digitales de control empresarial y tutela de la privacidad del trabajador de Federico Navarro Nieto de la Colección Aranzadi Derecho Laboral, más concretamente en el marco del uso de sistemas de videovigilancia sobre los trabajadores por parte de los empresarios. Para su elaboración, su autor emplea como base la Ley Orgánica 3/2018 de Protección de Datos, así como el Reglamento (UE) 2016/679, el Estauto de los Trabajadores y otras normas nacionales e internacionales. Además, hará referencia a resoluciones de gran relevancia sobre el caso, que marcarán las pautas a seguir sobre las cuestiones controversiales de la videovigilancia oculta y el empleo de los sistemas de seguridad con fines laborales.

The Longosomatidae, a poorly known polychaete family, includes only 23 recognized species; in this study, based on morphometric and taxonomic analyses, we describe a new species with three morphotypes: Heterospio variabilis from the Gulf of California, Mexico. The specimens examined exhibit large morphological variations but were clearly separated from close species due to a unique combination of morphological characters: chaetiger 9 as the first elongated chaetiger, four to eight branchial pairs; chaetae from chaetiger 10 forming rings in two rows, posterior row with thin and robust capillaries, anterior row with subuluncini, aristate spines, acicular spines and thick acicular spines. With the discriminant analysis, carried out on 11 morphometric characters, the presence of three morphological groups were recognized (Wilks’ lambda= 0.093, p = 0.0001). However, the variables selected to discriminate the specimens (partial Wilks’ lambda > 0.57) were correlated to their size: number of branchiae, body width, prostomium width, rate length CH9/CH1-CH8, length CH1-CH8 and length CH9 (r > 0.5). So, we concluded that they belong to a single species with three morphotypes: morpho A with eight branchial pairs, morpho B with 5–6–7 pairs and morpho C with 4 pairs. No correlations between the distribution of the distinct morphotypes along the eastern gulf shelf and the environmental conditions where they settle were detected.

Most of the therapeutic systems developed for managing chronic skin wounds lack adequate mechanical and hydration properties, primarily because they rely on a single component. This study addresses this issue by combining organic and inorganic materials to obtain hybrid films with enhanced mechanical behavior, adhesion, and fluid absorption properties. To that aim, chitosan/hydrolyzed collagen blends were mixed with halloysite/antimicrobial nanohybrids at 10% and 20% (w/w) using glycerin or glycerin/polyethylene glycol-1500 as plasticizers. The films were characterized through the use of Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), and electron microscopy. The mechanical properties were evaluated macroscopically using tensile tests, and at a nanoscale through atomic force microscopy (AFM) and nanoindentation. Thermodynamic studies were conducted to assess their hydrophilic or hydrophobic character. Additionally, in vitro cytocompatibility tests were performed on human keratinocytes. Results from FTIR, TGA, AFM and electron microscopy confirmed the hybrid nature of the films. Both tensile tests and nanomechanical measurements postulated that the nanohybrids improved the films’ toughness and adhesion and optimized the nanoindentation properties. All nanohybrid-loaded films were hydrophilic and non-cytotoxic, showcasing their potential for skin wound applications given their enhanced performance at the macro- and nanoscale.

The spatial patterns of taxonomic diversity of annelid polychaete species from the continental shelf in the Southern Gulf of Mexico were examined in this study. We used taxonomic distinctness and its spatial variations to explore the diversity patterns and how they change between Southern Gulf of Mexico regions. In addition, using taxonomic distinctness as a dissimilarity measure and Ward's Clustering, we characterized three distinct faunal assemblages. We also investigated patterns of richness, taxonomic distinctness, and distance decay of similarity between sampling stations as a ß-diversity measure. Finally, we examined the spatial relationships between polychaete assemblages and environmental variables to test the relative importance of spatial and environmental components in annelid polychaete community structure from the Southern Gulf of Mexico. We used a combination of eigenvector-based multivariate analyses (dbMEMs) and distance-based redundancy analysis (dbRDA) to quantify the relative importance of these explanatory variables on the spatial variations of taxonomic distinctness. The significance level of spatial and environmental components to the distribution of polychaete species showed that the combined effect of spatial processes and sediment characteristics explained a higher percentage of the variance than those parameters could alone.

To date, the need for biomaterials capable of improving the treatment of chronic skin wounds remains a clinical challenge. The aim of the present work is to formulate and characterize chitosan (Cs)/hydrolyzed collagen (HC) films as potential biomaterials with improved mechanical and hydration performances compared to single component formulations. Films were made by the solvent casting method, with or without glycerin and/or PEG1500 as plasticizers, resulting in a total of eight formulations. All films were characterized by their physico-chemical characteristics and their mechanical and hydration features. A full factorial design was also used to statistically assess the effect of HC concentration, type and concentration of plasticizers and their possible interactions on mechanical and swelling behaviors. Solid state characterization confirmed the hybrid nature of the films, with suggested electrostatic interactions between Cs and HC. Mechanical and swelling properties, along with the analysis of the experimental design, allowed the identification of formulations containing high HC concentration (2% w/v) and glycerin or glycerin/PEG1500 as more suitable candidates for skin wound treatment. Finally, viability assay of immortalized human keratinocytes (HaCaT) showed no statistical differences in cell survival compared to the complete culture medium, suggesting their potential as a promising tool for biomedical applications.

Copyright of Profesorado: Revista de Currículum y Formación del Profesorado is the property of Profesorado: Revista de Curriculum y Formacion del Profesorado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Ética y Cine Journal is the property of Etica y Cine Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The book review discusses Elena Llorente Arribas' monograph, "La Casa y el Imperio," which explores the relationship between family and the transatlantic Spanish empire. The book focuses on fifteen Biscayan oligarch families from four cities and towns and examines their strategies of empowerment and the transformation of Biscayan society. The monograph is divided into two parts, with the first part examining the development of the lineages and their commercial strategies, while the second part explores the cooperation and conflicts among the families for local hegemony. The review praises the extensive research and use of primary sources but criticizes the lack of theoretical support and engagement with global history debates. Overall, the book is seen as an important contribution to the study of prosopographies in global history and the localization of diverse elites within the Atlantic Hispanic World. [Extracted from the article]

Abstract Background Insulin signaling regulates cardiac substrate utilization and is implicated in physiological adaptations of the heart. Alterations in the signaling response within the heart are believed to contribute to pathological conditions such as type-2 diabetes and heart failure. While extensively investigated in several metabolic organs using phosphoproteomic strategies, the signaling response elicited in cardiac tissue in general, and specifically in the specialized cardiomyocytes, has not yet been investigated to the same extent. Methods Insulin or vehicle was administered to male C57BL6/JRj mice via intravenous injection into the vena cava. Ventricular tissue was extracted and subjected to quantitative phosphoproteomics analysis to evaluate the insulin signaling response. To delineate the cardiomyocyte-specific response and investigate the role of Tbc1d4 in insulin signal transduction, cardiomyocytes from the hearts of cardiac and skeletal muscle-specific Tbc1d4 knockout mice, as well as from wildtype littermates, were studied. The phosphoproteomic studies involved isobaric peptide labeling with Tandem Mass Tags (TMT), enrichment for phosphorylated peptides, fractionation via micro-flow reversed-phase liquid chromatography, and high-resolution mass spectrometry measurements. Results We quantified 10,399 phosphorylated peptides from ventricular tissue and 12,739 from isolated cardiomyocytes, localizing to 3,232 and 3,128 unique proteins, respectively. In cardiac tissue, we identified 84 insulin-regulated phosphorylation events, including sites on the Insulin Receptor (InsrY1351, Y1175, Y1179, Y1180) itself as well as the Insulin receptor substrate protein 1 (Irs1S522, S526). Predicted kinases with increased activity in response to insulin stimulation included Rps6kb1, Akt1 and Mtor. Tbc1d4 emerged as a major phosphorylation target in cardiomyocytes. Despite limited impact on the global phosphorylation landscape, Tbc1d4 deficiency in cardiomyocytes attenuated insulin-induced Glut4 translocation and induced protein remodeling. We observed 15 proteins significantly regulated upon knockout of Tbc1d4. While Glut4 exhibited decreased protein abundance consequent to Tbc1d4-deficiency, Txnip levels were notably increased. Stimulation of wildtype cardiomyocytes with insulin led to the regulation of 262 significant phosphorylation events, predicted to be regulated by kinases such as Akt1, Mtor, Akt2, and Insr. In cardiomyocytes, the canonical insulin signaling response is elicited in addition to regulation on specialized cardiomyocyte proteins, such as Kcnj11Y12 and DspS2597. Details of all phosphorylation sites are provided. Conclusion We present a first global outline of the insulin-induced phosphorylation signaling response in heart tissue and in isolated adult cardiomyocytes, detailing the specific residues with changed phosphorylation abundances. Our study marks an important step towards understanding the role of insulin signaling in cardiac diseases linked to insulin resistance. Graphical Abstract

IntroductionEnergy imbalance gap (EIG) is defined as the average daily difference between energy intake (EI) and energy expenditure (EE). This study aimed to examine the associations between EIG and sociodemographic and anthropometric variables in the adolescent population of eight Latin America countries.MethodsA total of 680 adolescents aged 15 to 18 were included in this study. The estimation of EI was based on two non-consecutive 24-h dietary recalls. EE was predicted from Schofield equations using physical activity level obtained through the long version of the International Physical Activity Questionnaire. Sociodemographic data and anthropometric measurements were also obtained. A descriptive analysis and multilevel linear regression models were used to examine associations between variables.ResultsThe mean EI, EE, and EIG were 2091.3 kcal, 2067.8 kcal, and 23.5 kcal, respectively. Argentina had the highest EI and EIG, whereas Chile had the lowest EI and EIG. Males had a higher EI (2262.4 kcal) and EE (2172.2 kcal) than females (1930.1 kcal and 2084.5 kcal), respectively (p

IntroductionMayaro Fever (MF) is a tropical disease caused by the Mayaro virus (MAYV), with outbreaks documented in Latin America.MethodsA hospital-based fever surveillance in Leticia, Colombian Amazon, collected sera from 1,460 patients aged 5-89 between December 2020 and April 2023.ResultsDengue and malaria were the main diagnoses (19.4 and 5.8%, respectively), leaving 71.4% of cases unidentified after testing. Metagenomic sequencing and real-time RT-qPCR testing identified MAYV in two patients (25-year-old male and an 80-year-old female) exhibiting typical symptoms, of MF including rash, joint pain, and fever. Phylogenetics analysis of these two viruses revealed a close relationship to Peruvian strains within the MAYV D genotype.DiscussionThe study of AFI in Leticia, Colombia, identified dengue as prevalent, with malaria, COVID-19, Influenza, and Zika viruses also detected. Despite extensive testing, most cases remained unexplained until metagenomic sequencing revealed MAYV, previously unseen in Colombia but known in neighboring countries.ConclusionThis study presents the first near full-length genomes of MAYV in Colombia, highlighting the need for further seroprevalence studies and enhanced surveillance to understand and control the spread of the virus in the region.

Pomegranate juice possesses therapeutic properties against metabolic syndrome. Microencapsulation of pomegranate juice (MPJ) may extend its shelf life; however, further research is necessary to ascertain its comparative efficacy with fresh juice. This work evaluated the effect of MPJ in an animal model with induced metabolic syndrome (MetS). MetS was induced in Male Wistar rats by administering 30% sucrose orally for 22 weeks. Once MetS was verified in the animals, seven groups were formed as follows: control (Ctrl); MetS; MetS + Placebo; Ctrl + MPJ; MetS + MPJ1 600; MetS + MPJ2 1800; and MetS + MPJ3 2900 mg/kg. Systolic and diastolic blood pressure, glucose, triglycerides, and total HDL-c levels in the MetS + MPJ groups improved significantly (p < 0.05) vs. the MetS group at the end of the study. Microencapsulation maintained the anti-metabolic-syndrome properties of pomegranate juice and could be used to control metabolic syndrome.