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Abstract Background Despite its proven prognostic value in different contexts, the precise implications of left atrial strain (LAS) assessment throughout different phases of the atrial cycle remain uncertain. A direct correlation between left atrial reservoir strain (LARS) and left ventricular global longitudinal strain (GLS) has been consistently demonstrated in several studies involving patients with various heart diseases. The objective of our study is to identify factors directly associated with LARS, left atrial conduction strain (LACS) and left atrial booster strain (LABS) in patients without cardiovascular (CV) disease. Methods Transthoracic echocardiographic examinations in patients without CV disease were prospectively selected in two tertiary hospitals echocardiography labs for clinical purposes. LAS, maximal and minimal left atrial (LA) volumes and left atrial ejection fraction (LAEF) were measured using the two-dimensional strain analysis package provided by the EchoPAC Plugging workstation (AFI LA). Results A total of 196 cases were included, median age of 54 (45–62) with 85 (43%) being men. The mean left ventricular ejection fraction (LVEF) was 61% ± 5, and the median GLS was − 18% (-17 to -20). Median indexed maximum volume of left atrium (LAVI) was 27 ml/m2 (22–31), and LAEF was 64% (58–70). The mean LARS biplane was 35,1% ± 8. Notably, LARS was greater in the 2-chamber view (36,1% ± 10) compared to the 4-chamber view (34,1% ± 8 p

Abstract Purpose Virtual Reality (VR) has proven to be an effective tool for motor (re)learning. Furthermore, with the current commercialization of low-cost head-mounted displays (HMDs), immersive virtual reality (IVR) has become a viable rehabilitation tool. Nonetheless, it is still an open question how immersive virtual environments should be designed to enhance motor learning, especially to support the learning of complex motor tasks. An example of such a complex task is triggering steps while wearing lower-limb exoskeletons as it requires the learning of several sub-tasks, e.g., shifting the weight from one leg to the other, keeping the trunk upright, and initiating steps. This study aims to find the necessary elements in VR to promote motor learning of complex virtual gait tasks. Methods In this study, we developed an HMD-IVR-based system for training to control wearable lower-limb exoskeletons for people with sensorimotor disorders. The system simulates a virtual walking task of an avatar resembling the sub-tasks needed to trigger steps with an exoskeleton. We ran an experiment with forty healthy participants to investigate the effects of first- (1PP) vs. third-person perspective (3PP) and the provision (or not) of concurrent visual feedback of participants’ movements on the walking performance – namely number of steps, trunk inclination, and stride length –, as well as the effects on embodiment, usability, cybersickness, and perceived workload. Results We found that all participants learned to execute the virtual walking task. However, no clear interaction of perspective and visual feedback improved the learning of all sub-tasks concurrently. Instead, the key seems to lie in selecting the appropriate perspective and visual feedback for each sub-task. Notably, participants embodied the avatar across all training modalities with low cybersickness levels. Still, participants’ cognitive load remained high, leading to marginally acceptable usability scores. Conclusions Our findings suggest that to maximize learning, users should train sub-tasks sequentially using the most suitable combination of person’s perspective and visual feedback for each sub-task. This research offers valuable insights for future developments in IVR to support individuals with sensorimotor disorders in improving the learning of walking with wearable exoskeletons

Abstract The earliest archaeological evidence from northern Africa dates to ca. 2.44 Ma. Nevertheless, the palaeoenvironmental setting of hominins living in this part of the continent at the Plio-Pleistocene transition remains poorly documented, particularly in comparison to eastern and southern Africa. The Guefaït-4 fossil site in eastern Morocco sheds light on our knowledge of palaeoenvironments in northern Africa. Our study reveals the oldest known presence of C4 plants in the northern part of the continent in a mosaic landscape that includes open grasslands, forested areas, wetlands, and seasonal aridity. This diverse landscape and resource availability likely facilitated the occupation of the region by mammals, including potentially hominins. Our regional-scale study provides a complementary perspective to global-scale studies and highlights the importance of considering the diversity of microhabitats within a given region when studying species-dispersal dynamics.

AbstractDespite the great interest in the development of a vaccine against African swine fever (ASF) in wild boar, the immunological mechanisms that induce animal protection are still unknown. For this purpose, tertiary lymphoid organs (TLOs) of wild boar were characterised and compared with mucosa-associated lymphoid tissues (MALTs) by histopathology, histomorphometry and immunohistochemistry (CD3, CD79, PAX5, LYVE1, fibronectin). In addition, real-time polymerase chain reaction (qPCR) and immunohistochemistry (p72) were used to evaluate the presence of ASF virus (ASFV) in blood and tissues samples, respectively. TLOs were observed in animals infected with a low-virulent ASFV isolate (LVI), animals co-infected with low and high-virulent ASFV isolates (LVI-HVI) and animals infected only with the high virulence isolate (HVI). TLOs in LVI and LVI-HVI groups were located adjacent to the mucosa and presented a similar structure to MALT. Immunoexpresion of p72 observed in the inflammatory cells adjacent to TLOs/MALTs confirmed its development and reactivity generated by ASF attenuated isolates. Immunohistochemical evaluation, based on cellular composition (T and B lymphocytes), and histomorphometrical study revealed a more pronounced maturation of TLOs/MALTs in the LVI-HVI group. It is currently unclear whether these formations play a protective role by contributing to local immunity in chronic inflammatory diseases. However, the structural similarities between TLOs and MALTs and the location of TLOs close to the mucosa suggest that they may perform a similar function, facilitating a local protective response. Nevertheless, further investigations are warranted to assess the cellular and humoral dynamics of these lymphoid organs induced by attenuated isolates.

Abstract Several studies published so far used highly selective image datasets from unclear sources to train computer vision models and that may lead to overestimated results, while those studies conducted in real-life remain scarce. To avoid image selection bias, we stacked convolutional and recurrent neural networks (CNN-RNN) to analyze complete optical coherence tomography (OCT) cubes in a row and predict diabetic macular edema (DME), in a real-world diabetic retinopathy screening program. A retrospective cohort study was carried out. Throughout 4-years, 5314 OCT cubes from 4408 subjects who attended to the diabetic retinopathy (DR) screening program were included. We arranged twenty-two (22) pre-trained CNNs in parallel with a bidirectional RNN layer stacked at the bottom, allowing the model to make a prediction for the whole OCT cube. The staff of retina experts built a ground truth of DME later used to train a set of these CNN-RNN models with different configurations. For each trained CNN-RNN model, we performed threshold tuning to find the optimal cut-off point for binary classification of DME. Finally, the best models were selected according to sensitivity, specificity, and area under the receiver operating characteristics curve (AUROC) with their 95% confidence intervals (95%CI). An ensemble of the best models was also explored. 5188 cubes were non-DME and 126 were DME. Three models achieved an AUROC of 0.94. Among these, sensitivity, and specificity (95%CI) ranged from 84.1–90.5 and 89.7–93.3, respectively, at threshold 1, from 89.7–92.1 and 80–83.1 at threshold 2, and from 80.2–81 and 93.8–97, at threshold 3. The ensemble model improved these results, and lower specificity was observed among subjects with sight-threatening DR. Analysis by age, gender, or grade of DME did not vary the performance of the models. CNN-RNN models showed high diagnostic accuracy for detecting DME in a real-world setting. This engine allowed us to detect extra-foveal DMEs commonly overlooked in other studies, and showed potential for application as the first filter of non-referable patients in an outpatient center within a population-based DR screening program, otherwise ended up in specialized care.

Se actualizaron las correlaciones existentes entre el valor N del ensayo de penetración estándar (Nspt) y las propiedades geotécnicas C, Φ y E de las arcillas plásticas del municipio Bayamo, en la provincia Granma. Se aplicaron el ensayo in situ de Penetración Estándar (SPT), ensayos físicos–mecánicos a los suelos, y se utilizaron procesamiento estadístico matemático mediante el software SPSS. Para ello el trabajo se divide en tres etapas diferenciadas, la primera encaminada a la búsqueda y revisión bibliográfica (repositorios académicos, revistas científicas, archivo técnico de la empresa), una segunda etapa enfocada al trabajo realizado (campo, laboratorio) y una tercera donde se recopiló y organizó la información obtenida para su posterior procesamiento estadístico. Se obtuvieron tres ecuaciones de correlación para este tipo de suelo en particular. Se concluyó que las arcillas presentan una alta confiabilidad por lo que se recomienda su uso para las obras de poca envergadura o en la etapa de ideas conceptuales de los proyectos a realizar en el municipio.

Summary: Cysteine proteases calpains contribute to heart failure (HF), but it remains unknown whether their inhibition provides any benefit compared to standard pharmacological treatment for HF. Here, we characterize the pharmacological properties of NPO-2270 (NPO) as a potent inhibitor of cysteine proteases. Then, we describe that acute administration of NPO in rodent models of transient ischemia at the time of reperfusion reduces myocardial infarction, while its chronic oral administration attenuates adverse remodeling and cardiac dysfunction induced by ischemic and non-ischemic pathological stimuli more effectively than enalapril when given at the same dose. Finally, we provide evidence showing that the effects of NPO correlate with calpain inhibition and the preservation of the T-tubule morphology, due at least in part to reduced cleavage of the calpain substrate junctophilin-2. Together, our data highlight the potential of cysteine protease inhibition with NPO as a therapeutic strategy for the treatment of heart failure.

African swine fever (ASF) poses a significant threat to domestic pigs and wild boar (Sus scrofa) populations, with the current epidemiological situation more critical than ever. The disease has spread across five continents, causing devastating losses in the swine industry. Although extensive research efforts are ongoing to develop an effective and safe vaccine, this goal remains difficult to achieve. Among the potential vaccine candidates, live attenuated viruses (LAVs) have emerged as the most promising option due to their ability to provide strong protection against experimental challenges. However, ASF virus (ASFV) is highly diverse, with genetic and phenotypic variations across different isolates, which differ in virulence. This study highlights the limitations of a natural LAV strain (Lv17/WB/Rie1), which showed partial efficacy against a highly virulent and partially heterologous isolate (Arm07; genotype II). However, the LAV's effectiveness was incomplete when tested against a more phylogenetically distant virus (Ken06.Bus; genotype IX). These findings raise concerns about the feasibility of developing a universal vaccine for ASFV in the near future, emphasizing the urgent need to assess the protective scope of LAV candidates across different ASFV isolates to better define their limitations.

IntroductionMedia health literacy emerges as a response to the vast array of informational disorders prevalent in media communications. Given the absence of a measurement tool for this type of literacy in Spanish-speaking communities, the aim of the present study is to conduct a cross-cultural adaptation of the Media Health Literacy (MeHLit) questionnaire into Spanish and to analyze its psychometric properties in a sample of nursing students.MethodsThe Spanish version of the MeHLit questionnaire (MeHLit-SV) was obtained through a process involving translation, back-translation, evaluation of the proposed items by a group of 22 experts, and a pilot study with 80 Spanish nursing students. Content validity was assessed using each item’s content validity index (CVI) and Aiken’s V (VdA), while internal consistency was evaluated through Cronbach’s Alpha.ResultsFollowing the translation and adaptation process, the final version of the MeHLit-SV comprised 21 items organized into five dimensions. The CVI values exceeded 0.82 for all items, and the overall content validity index (S-CVI) was 0.9. Furthermore, the results of Aiken’s V surpassed the threshold considered acceptable (0.70). After piloting, the questionnaire demonstrated high internal consistency with a Cronbach’s alpha value of 0.936.ConclusionThe findings of this research support the reliability and validity of the MeHLit-SV for use among nursing students to measure their level of media health literacy. This questionnaire, with satisfactory psychometric properties and ease of administration, is an useful tool for assessing whether individuals possess the necessary skills to accurately analyze health information they encounter on a daily basis.

Aim: Recent emergence of airway clearance devices (ACDs) as a treatment alternative for foreign body airway obstructions (FBAO) lacks substantial evidence on efficacy and safety. This study aimed to assess pediatric residents’ knowledge and skills in managing a simulated pediatric choking scenario, adhering to recommended protocols, and using LifeVac© and DeCHOKER© ACDs. Methods: Randomized controlled simulation trial, in which 60 pediatric residents from 3 different hospitals (median age 27 [25.0–29.9]; 76.7% female) were asked to solve an unannounced pediatric simulated choking scenario using three interventions to manage (randomized order): 1) following the recommended protocol of the European Resuscitation Council (encouraging to cough or combination of back blows and abdominal thrusts); 2) using LifeVac©; and 3) using DeCHOKER©. A Little Anne QCPR™ manikin (Laerdal Medical) was used. The variable compliance rate (%) was calculated according to the correct/incorrect execution of the steps constituting the proper actions for each test. Results: Participants demonstrated a correct compliance rate only ranging between 50–75% in following the recommended protocol for managing partial FBAO progressing to severe. Despite unfamiliarity with the ACDs, pediatric residents achieved rates between 75% and 100%, with no significant difference noted between the two devices (p = 0.173). Both scenarios were successfully resolved in under a minute, with LifeVac© demonstrating a significantly shorter response time compared to DeCHOKER© (39.2 [30.4–49.1] vs. 45.1s [33.7–59.2], p = 0.010). Conclusions: Only a minority of pediatric residents were able to adhere to the recommended FBAO protocol, whereas 70% of them were able to adequately use the ACDs. However, since a significant proportion could not, it seems that ACDs themselves do not address all issues.

Abstract In the wake of the COVID-19 pandemic caused by SARS-CoV-2, questions emerged about the potential effects of Bacillus Calmette-Guérin (BCG) vaccine on the immune response to SARS-CoV-2 infection, including the neurodegenerative diseases it may contribute to. To explore this, an experimental study was carried out in BCG-stimulated and non-stimulated k18-hACE2 mice challenged with SARS-CoV-2. Viral loads in tissues determined by RT-qPCR, histopathology in brain and lungs, immunohistochemical study in brain (IHC) as well as mortality rates, clinical signs and plasma inflammatory and coagulation biomarkers were assessed. Our results showed BCG-SARS-CoV-2 challenged mice presented higher viral loads in the brain and an increased frequency of neuroinvasion, with the greatest differences observed between groups at 3–4 days post-infection (dpi). Histopathological examination showed a higher severity of brain lesions in BCG-SARS-CoV-2 challenged mice, mainly consisting of neuroinflammation, increased glial cell population and neuronal degeneration, from 5 dpi onwards. This group also presented higher interstitial pneumonia and vascular thrombosis in lungs (3–4 dpi), BCG-SARS-CoV-2 mice showed higher values for TNF-α and D-dimer values, while iNOS values were higher in SARS-CoV-2 mice at 3–4 dpi. Results presented in this study indicate that BCG stimulation could have intensified the inflammatory and neurodegenerative lesions promoting virus neuroinvasion and dissemination in this experimental model. Although k18-hACE2 mice show higher hACE2 expression and neurodissemination, this study suggests that, although the benefits of BCG on enhancing heterologous protection against pathogens and tumour cells have been broadly demonstrated, potential adverse outcomes due to the non-specific effects of BCG should be considered.

Background: Nutritional assessment on admission of critical patients is of vital importance to determine critical patients in whom there is a risk of malnutrition. Currently, it has been detected in most of the patients admitted to the Intensive Care Unit (ICU) that 60% of the daily calories are not achieved. Nurses play an essential role in the comprehensive assessment of the patient, including the nutritional area; however, significant deficits have been detected in some knowledge regarding Enteral Nutrition (EN). Objective: We aim to determine the level of knowledge of nurses in the nutritional assessment of critically ill patients. Methodology: A systematic review of the scientific literature was conducted using the PRISMA statement. Between January 2017 and February 2023, articles were rescued from the electronic databases “Pubmed”, “Scopus” and “The Cochrane Library”, which analyzed the level of knowledge of ICU nurses regarding nutritional assessment. Results: Most of the results found showed that nurses had deficient levels of knowledge in relation to nutritional assessment and practices. Interventions related to nutritional assessment were scarce, in contrast to those associated with the management of Nasogastric Tube (NGT) or patient positioning. Conclusions: The level of knowledge described was low or inadequate in relation to the care associated with the nutritional assessment of critically ill patients. The use of scales to assess the risk of malnutrition was not reported. This study was prospectively registered at PROSPERO on 25/10/2023 (insert date) with registration number CRD: 42023426924.

Abstract We discuss the effective field theory (EFT) for nuclear beta decay. The general quark-level EFT describing charged-current interactions between quarks and leptons is matched to the nucleon-level non-relativistic EFT at the O MeV $$ \mathcal{O}\left(\textrm{MeV}\right) $$ momentum scale characteristic for beta transitions. The matching takes into account, for the first time, the effect of all possible beyond-the-Standard-Model interactions at the subleading order in the recoil momentum. We calculate the impact of all the Wilson coefficients of the leading and subleading EFT Lagrangian on the differential decay width in allowed beta transitions. As an example application, we show how the existing experimental data constrain the subleading Wilson coefficients corresponding to pseudoscalar, weak magnetism, and induced tensor interactions. The data display a 3.5 sigma evidence for nucleon weak magnetism, in agreement with the theory prediction based on isospin symmetry.

(1) Objective: The objective was to evaluate the quality of cardiopulmonary resuscitation (CPR, chest compressions and ventilations) when performed by a lone first responder on an infant victim via the over-the-head technique (OTH) with bag-mask ventilation in comparison with the standard lateral technique (LAT) position. (2) Methods: A randomized simulation crossover study in a baby manikin was conducted. A total of 28 first responders performed each of the techniques in two separate CPR tests (15:2 chest compressions:ventilations ratio), each lasting 5 min with a 15 min resting period. Quality CPR parameters were assessed using an app connected to the manikin. Those variables were related to chest compressions (CC: depth, rate, and correct CC point) and ventilation (number of effective ventilations). Additional variables included perceptions of the ease of execution of CPR. (3) Results: The median global CPR quality (integrated CC + V) was 82% with OTH and 79% with LAT (p = 0.94), whilst the CC quality was 88% with OTH and 80% with LAT (p = 0.67), and ventilation quality was 85% with OTH and 85% with LAT (p = 0.98). Correct chest release was significantly better with OTH (OTH: 92% vs. LAT: 62%, p < 0.001). There were no statistically significant differences in the remaining variables. Ease of execution perceptions favored the use of LAT over OTH. (4) Conclusions: Chest compressions and ventilations can be performed with similar quality in an infant manikin by lifeguards both with the standard recommended position (LAT) and the alternative OTH. This option could give some advantages in terms of optimal chest release between compressions. Our results should encourage the assessment of OTH in some selected cases and situations as when a lone rescuer is present and/or there are physical conditions that could impede the lateral rescue position.

Fullerene dimerization inside a peapod is analyzed at DFT level by characterizing the stationary points and deriving the energy profile of the initial and reversible process named phase 1. We find that the barriers for the radical cation mechanism are significantly lower than those found for the neutral pathway. The peapod is mainly providing one-dimensional confinement for the reaction to take place in a more efficient way. Car–Parrinello metadynamics simulations provide hints on structures for the initial steps of the irreversible phase 2 where bond formation and breaking lead to important structural reorganizations within the coalescence process.

Abstract We perform a model-independent analysis of top-philic New Physics scenarios, under the assumption that only effective operators involving top quarks are generated at tree level. Within the SMEFT framework, we derive indirect constraints on Wilson Coefficients by combining a large set of low-energy observables: B-meson and kaon decays, meson mixing observables, precision electroweak and Higgs measurements, anomalous magnetic moments, lepton flavour violating processes, lepton flavour universality tests, and measurements of the Cabibbo angle. We consider the renormalization group evolution of the operators and use the one-loop matching of the SMEFT onto the LEFT. The global analysis is then used to perform one-parameter, two-parameter, and global fits, as well as applications to explicit ultraviolet models. We find that the inclusion of measurements from different physics sectors reveals a strong interplay and complementarity among the observables. The resulting constraints are also compared to direct bounds provided by top quark productions at the LHC.

Background/Objectives: The burden of chronic kidney disease (CKD) is increasing, as is the prevalence of type 2 diabetes mellitus (T2DM). Post-hoc analyses of clinical trials support that sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptors agonists (GLP-1RAs) prevent CKD in T2DM patients. Methods: We used the Spanish primary care database BIFAP to perform a retrospective cohort study with a nested case-control analysis to assess the incidence, risk factors, and the effect of glucose-lowering drugs (GLDs) on the primary prevention of CKD. Results: From a cohort of 515,701 T2DM subjects (2.75 million person-years), we found 89,075 incident CKD cases, yielding an overall incidence rate (95%CI) of 324.3 (322.1–326.5) per 10,000 person-years. In the nested case–control analysis, gout, hyperuricemia, and hyperkalemia were the factors showing the highest AORs. Long-term users (≥3 years) of GLP1-RAs and SGLT-2i, compared to other GLDs, showed a decreased risk for CKD (AOR = 0.85; 95%CI: 0.73–0.99 and AOR = 0.89; 95%CI: 0.74–1.08, respectively), and for incident CKD at KDIGO stages G3-G5 (AOR = 0.72; 95%CI: 0.56–0.94 and AOR = 0.64; 95%CI: 0.46–0.91, respectively). Conclusions: In a real-world primary care setting, the long-term use of GLP-1RAs and SGLT-2i, but not other GLDs, appeared to decrease the risk of incident CKD in T2DM, supporting a role in primary prevention of CKD.

Recent geomorphological, paleoenvironmental, and chronological evidence allows for a reconstruction of the coasts of southwest Iberia during the first millennium BCE that accords with descriptions of the region offered by authors of antiquity, most notably the description by the fourth-century CE Roman writer R. F. Avienus in his poem Ora Maritima. This poem contains information that appears to date from the sixth century BCE regarding, for instance, the pre-Roman polity of Tartessos. The reliability of this work as a historical source has been questioned for decades. Critics argue that the information is pertinent to our understanding of the literary, rather than historiographical, context of the Late Roman Empire. However, philological as well as historical analyses reveal no clear cause to doubt the documentary value of the Ora Maritima. Furthermore, geomorphological research makes it possible to identify most place-names in the poem; for example, the city embraced by the river Tartessos, apparently the political and trade center of the realm, may likely have stood on the present-day spit of La Algaida, which was an isle in the first millennium BCE. While this hypothesis has been advanced elsewhere, this article offers an entirely new set of evidences to support it.1

IntroductionThe Spanish Emergency Medical Services, according to the model we know today, were formed during the 80s and 90s of the 20th century. The Health Emergency Service (EMS), 061 La Rioja, began to assist the population of La Rioja in November 1999. An essential part of the mission of the SES is the provision of care and the transfer of critical patients using advanced life support unit (ALSU) techniques. In daily practice, out-of-hospital emergency services are faced with situations in which they must deal with the care of serious or critically ill patients, in which the possibility of being able to channel peripheral vascular access as part of ALSU quickly may be difficult or impossible. In these cases, cannulation of intraosseous (IO) vascular access may be the key to early and adequate care.AimThis study aimed to determine the incidence and epidemiology use of IO vascular access in SES 061 La Rioja during the year 2022.Matherial and methodsWe performed observational retrospective cross-sectional studies conducted in 2022. It included a population of 4.364 possible patients as a total of interventions in the community of La Rioja in that year.ResultsA total of 0.66% of patients showed a clinical situation that required the establishment of IO vascular access to enable out-of-hospital stabilization; this objective was achieved in 41.3%. A total of 26.1% of patients who presented with cardiorespiratory arrest (CA) were stabilized, while 100% presented with shock and severe trauma.DiscussionIO vascular access provides a suitable route for out-of-hospital stabilization of critically ill patients when peripheral vascular access is difficult or impossible.

Resumen: Introducción-objetivos: en la formación de los residentes en ciencias de la salud resulta fundamental desarrollar un pensamiento bioético. Este reto docente debe adaptarse a las tecnologías actuales. Se analiza el curso telemático «Introducción a la bioética cotidiana para residentes de primer año». Pocas actividades de este tipo han sido diseñadas para residentes o analizadas con métodos cuantitativos. Material y métodos: los datos se extrajeron de la plataforma a distancia y de una encuesta de satisfacción de 3 ediciones (2021-2023). Se incluyeron variables del rendimiento del curso y la influencia del cambio de diseño tras la 1ª edición. Las variables cuantitativas fueron analizadas mediante distintos test estadísticos (R versión 4.2.0). Resultados: el curso fue completado por 1.268 alumnos/as (72% mujeres). La mayoría accedieron al menos al 75% del contenido audiovisual, no hubo diferencias entre módulos ni por sexo. Se registraron 4.132 intervenciones en el foro de debate, tras la 1ª edición la participación se incrementó significativamente, así como la satisfacción con la estructura y tiempos del curso. Un 57,3% de los alumnos/as presentaron una puntuación superior a 8/10 en el test inicial y más del 90% en el final. El 89% estuvo satisfecho con el aprendizaje. Conclusiones: El curso parece haber sido útil y formativo para los alumnos. La autogestión de los contenidos, así como el formato con píldoras audiovisuales de breve duración han sido bien valorados. Los métodos de e-deliberating siguen teniendo limitaciones para el debate bioético. A largo plazo podría verse un impacto en la calidad asistencial. Abstract: Introduction-objectives: In the training of Health Science residents, it is essential to develop bioethical thinking. This teaching challenge must be adapted to current technologies. The online course “Introduction to everyday bioethics for first-year residents” is analysed. Few activities of this type have been designed for residents or analysed using quantitative methods. Material and methods: Data were extracted from the online platform and from a satisfaction survey of 3 editions (2021-2023). Course performance variables and the influence of the design change after the 1st edition were included. Quantitative variables were analysed using different statistical tests (R version 4.2.0). Results: The course was completed by 1,268 students (72% female). Most accessed at least 75% of the audiovisual content; there were no differences between modules or by gender. After the first edition, participation increased significantly, as did satisfaction with the structure and timing of the course. 57.3% of the students scored more than 8/10 in the initial test and more than 90% in the final. 89% were satisfied with the learning. Conclusions: The course seems to have been useful and formative for the learners. The self-management of the content as well as the format with short audio-visual pills were well appreciated. The e-learning methods still have limitations for the bioethical debate. In the long term, an impact on the quality of care could be seen.

Abstract Understanding metal-metal bonding involving f-block elements has been a challenging goal in chemistry. Here we report a series of mixed-valence di-metallofullerenes, ThDy@C2n (2n = 72, 76, 78, and 80) and ThY@C2n (2n = 72 and 78), which feature single electron actinide-lanthanide metal-metal bonds, characterized by structural, spectroscopic and computational methods. Crystallographic characterization unambiguously confirmed that Th and Y or Dy are encapsulated inside variably sized fullerene carbon cages. The ESR study of ThY@D 3h (5)-C78 shows a doublet as expected for an unpaired electron interacting with Y, and a SQUID magnetometric study of ThDy@D 3h (5)-C78 reveals a high-spin ground state for the whole molecule. Theoretical studies further confirm the presence of a single-electron bonding interaction between Y or Dy and Th, due to a significant overlap between hybrid spd orbitals of the two metals.

Abstract Pancreatic cancer is one of the most challenging cancers due to its high mortality rates. Considering the late diagnosis and the limited survival benefit with current treatment options, it becomes imperative to optimize early detection, prognosis and prediction of treatment response. To address these challenges, significant research efforts have been undertaken in recent years to develop liquid-biopsy-based biomarkers for pancreatic cancer. In particular, an increasing number of studies point to cell-free DNA (cfDNA) methylation analysis as a promising non-invasive approach for the discovery and validation of epigenetic biomarkers with diagnostic or prognostic potential. In this review we provide an update on recent advancements in the field of cfDNA methylation analysis in pancreatic cancer. We discuss the relevance of DNA methylation in the context of pancreatic cancer, recent cfDNA methylation research, its clinical utility, and future directions for integrating cfDNA methylation analysis into routine clinical practice.

Abstract Background Foreign body reaction in brain tissue is a very rare immune response that has not been well studied. Hemostatic material has been reported as a possible trigger of this response in other organs and could be detected by [18F]fluorodeoxyglucose positron emission tomography/computerized tomography ([18F]FDG PET/CT), but there is no reported experience about the role of [18F]fluorocholine in this finding. [18F]Fluorocholine has the potential to differentiate viable central nervous system tumors from other entities, so it is frequently used in the follow-up of neurosurgery patients. Case presentation A right frontoparietal neoplastic lesion was found in a young-aged patient with analgesic refractory headache. Surgical resection and postsurgical radiotherapy were performed, and the pathologist analysis turned out a cellular ependymoma with signs of anaplasia. In the follow-up, an magnetic resonance imaging (MRI) showed a suspicious lesion, so a [18F]fluorocholine PET/CT was performed. Increased uptake was described in the right parietal region on the margin of the residual cystic lesion. The patient got a complete resection which was confirmed later by MRI. In the pathology analysis, a focally congestive cerebral parenchyma with a central histiocytic reaction to a foreign body area was described. Conclusions Following the experience of the current case report, [18F]fluorocholine PET/CT could also show a false positive related to foreign body reaction. This entity should be considered to avoid unnecessary major surgery on our patients.

Abstract Background and Aims The triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD. Methods The relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9−/− mice for therapeutic and mechanistic studies on endotoxemia-induced cardiac dysfunction in mice. Results In sepsis patients, elevated plasma S100A8/A9 was associated with left-ventricular (LV) systolic dysfunction and increased SOFA score. In wild-type mice, 5 mg/kg of bacterial lipopolysaccharide (LPS) induced rapid plasma S100A8/A9 increase and acute LV dysfunction. Two ABR-238901 doses (30 mg/kg) administered intraperitoneally with a 6 h interval, starting directly after LPS or at a later time-point when LV dysfunction is fully established, efficiently prevented and reversed the phenotype, respectively. In contrast, dexamethasone did not improve cardiac function compared to PBS-treated endotoxemic controls. S100A8/A9 inhibition potently reduced systemic levels of inflammatory mediators, prevented upregulation of inflammatory genes and restored mitochondrial function in the myocardium. The S100A9−/− mice were protected against LPS-induced LV dysfunction to an extent comparable with pharmacologic S100A8/A9 blockade. The ABR-238901 treatment did not induce an additional improvement of LV function in the S100A9−/− mice, confirming target specificity. Conclusion Elevated S100A8/A9 is associated with the development of LV dysfunction in severe sepsis patients and in a mouse model of endotoxemia. Pharmacological blockade of S100A8/A9 with ABR-238901 has potent anti-inflammatory effects, mitigates myocardial dysfunction and might represent a novel therapeutic strategy for patients with severe sepsis. Graphical Abstract

Abstract Mirror therapy is applied to reduce phantom pain and as a rehabilitation technique in post-stroke patients. Using Virtual Reality and head-mounted displays this therapy can be performed in virtual scenarios. However, for its efficient use in clinical settings, some hardware limitations need to be solved. A new system to perform mirror therapy in virtual scenarios for post-stroke patients is proposed. The system requires the patient a standalone virtual reality headset with hand-tracking features and for the rehabilitator an external computer or tablet device. The system provides functionalities for the rehabilitator to prepare and follow-up rehabilitation sessions and a virtual scenario for the patient to perform rehabilitation. The system has been tested on a real scenario with the support of three experienced rehabilitators and considering ten post-stroke patients in individual sessions focused on upper limb motor rehabilitation. The development team observed all the sessions and took note of detected errors regarding technological aspects. Solutions to solve detected problems will be proposed and evaluated in terms of feasibility, performance cost, additional system cost, number of solved issues, new limitations, or advantages for the patient. Three types of errors were detected and solved. The first error is related to the position of the hands relative to the head-mounted display. To solve it the exercise area can be limited to avoid objectives that require turning the head too far. The second error is related to the interaction between the hands and the virtual objects. It can be solved making the main hand non-interactive. The last type of error is due to patient limitations and can be mitigated by having a virtual hand play out an example motion to bring the patient’s attention back to the exercise. Other solutions have been evaluated positively and can be used in addition or instead of the selected ones. For mirror therapy based on virtual reality to be efficient in post-stroke rehabilitation the current head-mounted display-based solutions need to be complemented with specific strategies that avoid or mitigate the limitations of the technology and the patient. Solutions that help with the most common issues have been proposed.

Introduction: Extracorporeal membrane oxygenation (ECMO) improves infant survival outcomes after cardiac arrest. If not feasible at the place of arrest, victims must be transported to a suitable room to perform ECMO while effective, sustained resuscitation maneuvers are performed. The objective of this simulation study was to compare the quality of resuscitation maneuvers on an infant manikin during simulated transfer on a stretcher (stretcher test) within a hospital versus standard stationary resuscitation maneuvers (control test). Methods: A total of 26 nursing students participated in a randomized crossover study. In pairs, the rescuers performed two 2 min tests, consisting of five rescue breaths followed by cycles of 15 compressions and two breaths. The analysis focused on CPR variables (chest compression and ventilation), CPR quality, the rate of perceived exertion and the distance covered. Results: No differences were observed in the chest compression quality variable (82 ± 10% versus 84 ± 11%, p = 0.15). However, significantly worse values were observed in the test for ventilation quality on the stretcher (18 ± 14%) compared to the control test (28 ± 21%), with a value of p = 0.030. Therefore, the overall CPR quality was worse in the stretcher test (50 ± 9%) than in the control test (56 ± 13%) (p = 0.025). Conclusions: Infant CPR performed by nursing students while walking alongside a moving stretcher is possible. However, in this model, the global CPR quality is less due to the low ventilation quality.

El sistema de apoyos al aprendizaje necesita de pautas metodológicas para su aplicación en el proceso de enseñanza-aprendizaje, desde la perspectiva de la neurodidáctica se propicia el aseguramiento del aprendizaje en los estudiantes universitarios mediante la aplicación de métodos de enseñanza productivos; resulta necesario evaluar la motivación, la representación de los contenidos de enseñanza, y la acción y expresión. Es propósito de este artículo identificar dimensiones e indicadores que aseguren el proceso de apoyos al aprendizaje de estudiantes universitarios mediante la utilización de la neurodidáctica y facilite a los profesores vías para su desempeño creativo en el aula.

Abstract The relevance and importance that the topic of Digital Competences for Teachers (DCT) has gained is evident both in the field of training and in research, as can be seen by the increase in the amount of research and meta-analysis carried out on this topic. This article presents the results of an ex post facto research with a cross-sectional research design, based on a descriptive and hypothesis-testing approach. A total of 6,664 teachers from different Latin American universities participated in the self-knowledge they have regarding their Digital Teaching Competence (DTC) according to the DigCompEdu framework of the European Union. Among the results obtained, it is worth noting the intermediate level of digital competences reported by the teachers surveyed, with significant differences with respect to different key variables for their development. Therefore, we conclude by reflecting on the need to establish teacher training plans in this area.

Abstract Background Pancreatic cancer is the most lethal cancer with a dismal prognosis mainly due to diagnosis at advanced stage and ineffective treatments. CA19-9 levels and computed tomography (CT) imaging are the main standard criteria for evaluating disease progression and treatment response. In this study we explored liquid biopsy-based epigenetic biomarkers for prognosis and monitoring disease in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Methods Plasma samples were collected from 44 mPDAC patients at the time of diagnosis, and in 15 of them, additional samples were obtained during follow-up of the disease. After cell-free DNA (cfDNA), isolation circulating levels of methylated NPTX2, SPARC, BMP3, SFRP1 and TFPI2 genes were measured using digital droplet PCR (ddPCR). BEAMing technique was performed for quantitation of RAS mutations in cfDNA, and CA19-9 was measured using standard techniques. Results NPTX2 was the most highly and frequently methylated gene in cfDNA samples from mPDAC patients. Higher circulating NPTX2 methylation levels at diagnosis were associated with poor prognosis and efficiently stratified patients for prediction of overall survival (6.06% cut-off, p = 0.0067). Dynamics of circulating NPTX2 methylation levels correlated with disease progression and response to therapy and predicted better than CA19-9 the evolution of disease in mPDAC patients. Remarkably, in many cases the disease progression detected by CT scan was anticipated by an increase in circulating NPTX2 methylation levels. Conclusions Our study supports circulating NPTX2 methylation levels as a promising liquid biopsy-based clinical tool for non-invasive prognosis, monitoring disease evolution and response to treatment in mPDAC patients.

This paper reviews the importance of Cajal’s neuronal theory (the Neuron Doctrine) and the origin and importance of the idea of brain plasticity that emerges from this theory. We first comment on the main Cajal’s discoveries that gave rise and confirmed his Neuron Doctrine: the improvement of staining techniques, his approach to morphological laws, the concepts of dynamic polarisation, neurogenesis and neurotrophic theory, his first discoveries of the nerve cell as an independent cell, his research on degeneration and regeneration and his fight against reticularism. Second, we review Cajal’s ideas on brain plasticity and the years in which they were published, to finally focus on the debate on the origin of the term plasticity and its conceptual meaning, and the originality of Cajal’s proposal compared to those of other authors of the time.

Intrapancreatic accessory spleen (IPAS) is one of the most frequent congenital splenic anomalies in humans; however, studies in veterinary medicine are scarce. This study aimed to describe the macroscopic, histopathological and immunohistochemical features of 11 suspected cases of IPAS in wild boar piglets of 3–4 months old. Seven of the 11 animals were immunised with a low virulence isolate of African swine fever virus (ASFV) and subsequently challenged with a highly virulent ASFV isolate (LVI-HVI group). The remaining four animals were exclusively infected with a highly virulent isolate of ASFV (HVI group). Grossly, lesions comprised focal or multifocal reddish areas of variable shape, located on the surface of the pancreatic tail or within the parenchyma. Histological and immunohistochemical studies (anti-CD79 and CD3) confirmed the presence of IPAS in eight of the 11 cases. IPAS shared the same histological structure and alterations as those observed in the original spleen. The immunohistochemical study against ASFV revealed the presence of VP72+ cells in both the spleen and IPAS of seven of the eight piglets. The results of this study describe for the first time the presence of IPAS in ASFV infection of wild boar (Sus scrofa) regardless the isolate and suggest that the infection may induce the development of ectopic splenic tissue due to an increased demand for phagocytic cells from the reticuloendothelial system. However, further studies are needed to understand the immunological mechanisms that trigger the formation of these accessory organs.

Abstract Background The brand-new anti-choking devices (LifeVac® and DeCHOKER®) have been recently developed to treat Foreign Body Airway Obstruction (FBAO). However, the scientific evidence around these devices that are available to the public is limited. Therefore, this study aimed to assess the ability to use the LifeVac® and DeCHOKER® devices in an adult FBAO simulated scenario, by untrained health science students. Methods Forty-three health science students were asked to solve an FBAO event in three simulated scenarios: 1) using the LifeVac®, 2) using the DeCHOKER®, and 3) following the recommendations of the current FBAO protocol. A simulation-based assessment was used to analyze the correct compliance rate in the three scenarios based on the correct execution of the required steps, and the time it took to complete each one. Results Participants achieved correct compliance rates between 80–100%, similar in both devices (p = 0.192). Overall test times were significantly shorter with LifeVac® than DeCHOKER® device (36.6 sec. [31.9–44.4] vs. 50.4 s [36.7–66.9], p

Abstract Succinate is enhanced during initial reperfusion in blood from the coronary sinus in ST-segment elevation myocardial infarction (STEMI) patients and in pigs submitted to transient coronary occlusion. Succinate levels might have a prognostic value, as they may correlate with edema volume or myocardial infarct size. However, blood from the coronary sinus is not routinely obtained in the CathLab. As succinate might be also increased in peripheral blood, we aimed to investigate whether peripheral plasma concentrations of succinate and other metabolites obtained during coronary revascularization correlate with edema volume or infarct size in STEMI patients. Plasma samples were obtained from peripheral blood within the first 10 min of revascularization in 102 STEMI patients included in the COMBAT-MI trial (initial TIMI 1) and from 9 additional patients with restituted coronary blood flow (TIMI 2). Metabolite concentrations were analyzed by 1H-NMR. Succinate concentration averaged 0.069 ± 0.0073 mmol/L in patients with TIMI flow ≤ 1 and was significantly increased in those with TIMI 2 at admission (0.141 ± 0.058 mmol/L, p

Introduction: Thrombotic microangiopathies (TMA) are rare diseases usually presenting with renal, haematological, neurologic and cardiovascular involvement and nonspecific but severe symptoms. A registry of TMA cases managed in Spanish paediatric intensive care units (the MATUCIP Registry) was established with the aim of gaining knowledge on their clinical characteristics, diagnosis and acute-phase treatment. Methods: We conducted a prospective multicentre observational study in 20 paediatric intensive care units (PICUs) in Spain from January 2017 to December 2021 in children aged more than 1 month with TMAs, who were followed up through the discharge from the PICU. Results: The sample included 97 patients (51.5% female) with a median age of 2.6 years (interquartile range [IQR], 1.6–5.7). The initial manifestations were gastrointestinal (74.2%), respiratory (14.4%), fever (5.2%), neurologic (3.1%) and other (3.1%). At admission, 75.3% of patients had microangiopathic haemolytic anaemia, 95.9% thrombocytopenia and 94.8% acute kidney injury. Of the total sample, 57.7% of patients received a diagnosis of Shiga toxin-associated haemolytic uraemic syndrome (HUS), 14.4% of Streptococcus pneumoniae-associated HUS, 15.6% of atypical HUS, 10.3% of secondary TMA and 2.1% of thrombotic thrombocytopenic purpura. Eighty-seven patients (89.7%) developed arterial hypertension, and 49.5% gastrointestinal, 22.7% respiratory, 25.8% neurologic and 12.4% cardiac manifestations. Also, 60.8% required renal replacement therapy and 2.1% plasma exchange. Twenty patients received eculizumab. The median PICU stay was 8.5 days (IQR, 5–16.5). Two children died. Conclusions: The MATUCIP registry demonstrates the clinical variability of TMA cases requiring admission to the PICU. Knowledge of the presentation and outcomes of TMAs can facilitate early aetiological diagnosis. This registry can help improve our understanding of the clinical spectrum of these diseases, for which there is a dearth of published data. Resumen: Introducción: Las microangiopatías trombóticas (MAT) son entidades infrecuentes que suelen causar afectación renal, hematológica, neurológica y cardiovascular, con síntomas inespecíficos pero graves. Con la finalidad de mejorar el conocimiento de sus características clínicas, proceso diagnóstico y tratamiento en la fase aguda, se ha creado el registro de MAT en las Unidades de Cuidados Intensivos Pediátricos (UCIP) de España (Registro MATUCIP). Pacientes y métodos: Estudio observacional, multicéntrico realizado en 20 UCIP españolas desde enero 2017 hasta diciembre de 2021 que incluyó niños mayores de 1 mes con diagnóstico de MAT y seguimiento hasta el alta de UCIP. Resultados: Se incluyeron 97 pacientes (51,5% mujeres), con mediana de edad de 2,6 años (RIQ 1,6–5,7). La clínica inicial fue de tipo gastrointestinal (74,2%), respiratoria (14,4%), cuadro febril (5,2%), neurológica (3,1%) y otras (3,1%). Al ingreso, 75,3% presentaban anemia hemolítica microangiopática, 95,9% trombocitopenia y 94,8% daño renal agudo. Fueron diagnosticados de Síndrome Hemolítico Urémico (SHU) asociado a Escherichia coli productora de toxina Shiga 57,7%, SHU por Streptococcus pneumoniae 14,4%, SHU atípico 15,6%, MAT secundaria 10,3% y púrpura trombocitopénica trombótica 2,1%. Desarrollaron hipertensión arterial 89,7%, manifestaciones digestivas 49,5%, respiratorias 22,7%, neurológicas 25,8% y cardiacas 12,4%. El 60,8% requirieron depuración extrarrenal y 2,1% plasmaféresis. Recibieron eculizumab 20 pacientes. La mediana de estancia en UCIP fue 8,5 días (RIQ 5–16,5). Dos niños fallecieron. Conclusiones: El registro MATUCIP muestra la variabilidad clínica de las MAT que ingresan en UCIP. Conocer la forma de presentación y evolución de las MAT puede facilitar el diagnóstico etiológico precoz. Este registro permite conocer mejor el espectro clínico de estas entidades donde los datos publicados son escasos.

Succinate dehydrogenase inhibition with malonate during initial reperfusion reduces myocardial infarct size in both isolated mouse hearts subjected to global ischemia and in in situ pig hearts subjected to transient coronary ligature. However, the long-term effects of acute malonate treatment are unknown. Here, we investigated whether the protective effects of succinate dehydrogenase inhibition extend to a reduction in scar size and adverse left ventricular remodeling 28 days after myocardial infarction. Initially, ten wild-type mice were subjected to 45 min of left anterior descending coronary artery (LAD) occlusion, followed by 24 h of reperfusion, and were infused during the first 15 min of reperfusion with saline with or without disodium malonate (10 mg/kg/min, 120 μL/kg/min). Malonate-treated mice depicted a significant reduction in infarct size (15.47 ± 3.40% of area at risk vs. 29.34 ± 4.44% in control animals, p < 0.05), assessed using triphenyltetrazolium chloride. Additional animals were then subjected to a 45 min LAD ligature, followed by 28 days of reperfusion. Treatment with a single dose of malonate during the first 15 min of reperfusion induced a significant reduction in scar area, measured using Picrosirius Red staining (11.94 ± 1.70% of left ventricular area (n = 5) vs. 23.25 ± 2.67% (n = 9), p < 0.05), an effect associated with improved ejection fraction 28 days after infarction, as determined using echocardiography, and an attenuated enhancement in expression of the pro-inflammatory and fibrotic markers NF-κB and Smad2/3 in remote myocardium. In conclusion, a reversible inhibition of succinate dehydrogenase with a single dose of malonate at the onset of reperfusion has long-term protective effects in mice subjected to transient coronary occlusion.

Introduction: Glycogen synthase kinase 3 (GSK-3) has been proposed as a novel cancer target due to its regulating role in both tumor and immune cells. However, the connection between GSK-3 and immunoevasive contexture, including tumor budding (TB) has not been previously examined. Methods: we investigated the expression levels of total GSK-3 as well as its isoforms (GSK-3β and GSK-3α) and examined their potential correlation with TB grade and the programmed cell death-ligand 1 (PD-L1) in colorectal cancer (CRC) tumor samples. Additionally, we compared the efficacy of GSK-3-inhibition with PD-1/PD-L1 blockade in humanized patient-derived (PDXs) xenografts models of high-grade TB CRC. Results: we show that high-grade (BD3) TB CRC is associated with elevated expression levels of total GSK-3, specifically the GSK-3β isoform, along with increased expression of PD-L1 in tumor cells. Moreover, we define an improved risk stratification of CRC patients based on the presence of GSK-3+/PD-L1+/BD3 tumors, which are associated with a worse prognosis. Significantly, in contrast to the PD-L1/PD-1 blockade approach, the inhibition GSK-3 demonstrated a remarkable enhancement in the antitumor response. This was achieved through the reduction of tumor buds via necrosis and apoptosis pathways, along with a notable increase of activated tumor-infiltrating CD8+ T cells, NK cells, and CD4- CD8- T cells. Conclusions: our study provides compelling evidence for the clinical significance of GSK-3 expression and TB grade in risk stratification of CRC patients. Moreover, our findings strongly support GSK-3 inhibition as an effective therapy specifically targeting high-grade TB in CRC.

Extracellular matrix (ECM) is an active player in cardiovascular calcification (CVC), a major public health issue with an unmet need for effective therapies. Lysyl oxidase (LOX) conditions ECM biomechanical properties; thus, we hypothesized that LOX might impact on mineral deposition in calcific aortic valve disease (CAVD) and atherosclerosis. LOX was upregulated in calcified valves from two cohorts of CAVD patients. Strong LOX immunostaining was detected surrounding calcified foci in calcified human valves and atherosclerotic lesions colocalizing with RUNX2 on valvular interstitial cells (VICs) or vascular smooth muscle cells (VSMCs). Both LOX secretion and organized collagen deposition were enhanced in calcifying VICs exposed to osteogenic media. β-aminopropionitrile (BAPN), an inhibitor of LOX, attenuated collagen deposition and calcification. VICs seeded onto decellularized matrices from BAPN-treated VICs calcified less than cells cultured onto control scaffolds; instead, VICs exposed to conditioned media from cells over-expressing LOX or cultured onto LOX-crosslinked matrices calcified more. Atherosclerosis was induced in WT and transgenic mice that overexpress LOX in VSMC (TgLOXVSMC) by AAV-PCSK9D374Y injection and high-fat feeding. In atherosclerosis-challenged TgLOXVSMC mice both atherosclerosis burden and calcification assessed by near-infrared fluorescence (NIRF) imaging were higher than in WT mice. These animals also exhibited larger calcified areas in atherosclerotic lesions from aortic arches and brachiocephalic arteries. Moreover, LOX transgenesis exacerbated plaque inflammation, and increased VSMC cellularity, the rate of RUNX2-positive cells and both connective tissue content and collagen cross-linking. Our findings highlight the relevance of LOX in CVC and postulate this enzyme as a potential therapeutic target for CVC.

This study presents an exceptional collection of 54 Late Pleistocene human remains that correspond to at least three Neanderthal individuals from Simanya Gran, the main gallery of Cova Simanya, located in the northeastern Iberian Peninsula. The collection comprised 53 unpublished remains that were unearthed during the 1970s and an additional tooth discovered during 2021 excavations. The specimens represent an adult with a small stature, a periadolescent aged approximately 11.5 years, and an immature individual aged approximately 7.7 years, thus offering a more complete demographic perspective. The collection encompasses diverse anatomical parts including upper and lower dentition, mandible, vertebrae, and limb bones from both the upper and lower extremities. Attempts to extract aDNA were unsuccessful. Renewed archaeological investigations at Cova Simanya have facilitated the reevaluation of the original stratigraphic context of these remains, leading to the discovery of the additional tooth, aligning with the periadolescent individual. This assemblage is currently the most extensive Neanderthal collection from the northeastern Mediterranean Iberia, offering invaluable insights into the morphology and evolutionary trajectory of Late Pleistocene hominins. Hence, Simanya Neanderthals will enhance our understanding of Neanderthal demographics and evolution, paving the way for an in-depth examination of the morphological diversity and evolutionary context of Iberian Neanderthals.

Resumen: Introducción: el ideario popular, la diseminación a través de redes sociales o la «costumbre» han propiciado diversos mitos sobre el ahogamiento y los incidentes acuáticos que no están basados en evidencias y pueden tener efectos colaterales o limitan la comprensión de este fenómeno. El objetivo de este trabajo ha sido analizar el origen de los mitos más frecuentes relacionados con los incidentes acuáticos y ofrecer una perspectiva científica para su refutación. Materiales y métodos: doce expertos de las Ciencias de la Salud mediante un grupo nominal realizaron el cribado de conceptos en 3 fases: 1ª revisión literatura científica en PubMed en la que se abordasen conceptos erróneos u obsoletos relacionados a los incidentes en entornos acuáticos, 2ª el grupo elaboró un listado de 16 ítems susceptibles de analizar y 3ª se seleccionaron por consenso los mitos considerados más relevantes. Resultados: mediante consenso de expertos y las evidencias disponibles, 10 ítems fueron identificados como potenciales generadores de conceptos erróneos o mitos: el «corte de digestión», el uso de flotadores para prevenir el ahogamiento, hiperventilar antes de bucear, las implicaciones de la bandera roja en las playas, el proceso de ahogamiento, la principal función de los socorristas, orinar sobre picaduras de medusa, la terminología sobre ahogamiento y la reanimación de ahogados. Conclusión: en el ámbito del ahogamiento se sigue utilizando terminología obsoleta y existen creencias populares erróneas que deberían ser actualizadas y desmitificadas, ya que esto podría contribuir a disminuir la incidencia del ahogamiento y sus secuelas. Abstract: Introduction: Popular ideology, dissemination by social networks or the “custom” have fostered numerous myths about drowning and aquatic incidents that are not based on evidence and may be harmful or limit the understanding of this phenomenon. The aim of this paper is to analyze the origin of the most frequent myths related to aquatic incidents and to offer a scientific perspective for their refutation. Materials and methods: Twelve experts in the health sciences by means of a nominal group carried out the screening of concepts in three phases: 1st review of scientific literature in PUBMED in which erroneous or obsolete concepts related to incidents in aquatic environments were addressed, 2nd phase the nominal group elaborated an initial list of 16 items to be analyzed, 3rd phase the final list was refined to 1 by universal consensus of the nominal group. Results: Through expert consensus and available evidence, ten items were identified as potential generators of misconceptions or myths: the “digestion cut-off”, the use of floats to prevent drowning, hyperventilating before diving, the implications of the red flag on beaches, the drowning process, the main role of lifeguards, urinating on jellyfish stings, drowning terminology, and resuscitation of drowned persons. Conclusion: In the field of drowning, obsolete terminology continues to be used and there are erroneous popular beliefs that should be updated and demystified, as this could contribute to reduce the incidence of drowning and its sequelae.

Abstract The muon anomalous magnetic moment continues to attract attention due to the possible tension between the experimentally measured value and the theoretical Standard Model prediction. With the aim to reduce the uncertainty on the hadronic light-by-light contribution to the magnetic moment, we derive short-distance constraints in the Melnikov-Vainshtein regime which are useful for data-driven determinations. In this kinematical region, two of the four electromagnetic currents are close in the four-point function defining the hadronic light-by-light tensor. To obtain the constraints, we develop a systematic operator product expansion of the tensor in question to next-to-leading order in the expansion in operators. We evaluate the leading in α s contributions and derive constraints for the next-to-leading operators that are also valid nonperturbatively.

Abstract Background Alzheimer’s disease (AD) is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists. Neuroinflammation is central to the pathology progression, with evidence suggesting that microglia-released galectin-3 (gal3) plays a pivotal role by amplifying neuroinflammation in AD. However, the possible involvement of gal3 in the disruption of neuronal network oscillations typical of AD remains unknown. Methods Here, we investigated the functional implications of gal3 signaling on experimentally induced gamma oscillations ex vivo (20–80 Hz) by performing electrophysiological recordings in the hippocampal CA3 area of wild-type (WT) mice and of the 5×FAD mouse model of AD. In addition, the recorded slices from WT mice under acute gal3 application were analyzed with RT-qPCR to detect expression of some neuroinflammation-related genes, and amyloid-β (Aβ) plaque load was quantified by immunostaining in the CA3 area of 6-month-old 5×FAD mice with or without Gal3 knockout (KO). Results Gal3 application decreased gamma oscillation power and rhythmicity in an activity-dependent manner, which was accompanied by impairment of cellular dynamics in fast-spiking interneurons (FSNs) and pyramidal cells. We found that the gal3-induced disruption was mediated by the gal3 carbohydrate-recognition domain and prevented by the gal3 inhibitor TD139, which also prevented Aβ42-induced degradation of gamma oscillations. Furthermore, the 5×FAD mice lacking gal3 (5×FAD-Gal3KO) exhibited WT-like gamma network dynamics and decreased Aβ plaque load. Conclusions We report for the first time that gal3 impairs neuronal network dynamics by spike-phase uncoupling of FSNs, inducing a network performance collapse. Moreover, our findings suggest gal3 inhibition as a potential therapeutic strategy to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline.

Abstract Background C3G is a guanine nucleotide exchange factor (GEF) that activates Rap1 to promote cell adhesion. Resting C3G is autoinhibited and the GEF activity is released by stimuli that signal through tyrosine kinases. C3G is activated by tyrosine phosphorylation and interaction with Crk adaptor proteins, whose expression is elevated in multiple human cancers. However, the molecular details of C3G activation and the interplay between phosphorylation and Crk interaction are poorly understood. Methods We combined biochemical, biophysical, and cell biology approaches to elucidate the mechanisms of C3G activation. Binding of Crk adaptor proteins to four proline-rich motifs (P1 to P4) in C3G was characterized in vitro using isothermal titration calorimetry and sedimentation velocity, and in Jurkat and HEK293T cells by affinity pull-down assays. The nucleotide exchange activity of C3G over Rap1 was measured using nucleotide-dissociation kinetic assays. Jurkat cells were also used to analyze C3G translocation to the plasma membrane and the C3G-dependent activation of Rap1 upon ligation of T cell receptors. Results CrkL interacts through its SH3N domain with sites P1 and P2 of inactive C3G in vitro and in Jurkat and HEK293T cells, and these sites are necessary to recruit C3G to the plasma membrane. However, direct stimulation of the GEF activity requires binding of Crk proteins to the P3 and P4 sites. P3 is occluded in resting C3G and is essential for activation, while P4 contributes secondarily towards complete stimulation. Tyrosine phosphorylation of C3G alone causes marginal activation. Instead, phosphorylation primes C3G lowering the concentration of Crk proteins required for activation and increasing the maximum activity. Unexpectedly, optimal activation also requires the interaction of CrkL-SH2 domain with phosphorylated C3G. Conclusion Our study revealed that phosphorylation of C3G by Src and Crk-binding form a two-factor mechanism that ensures tight control of C3G activation. Additionally, the simultaneous SH2 and SH3N interaction of CrkL with C3G, required for the activation, reveals a novel adaptor-independent function of Crk proteins relevant to understanding their role in physiological signaling and their deregulation in diseases. Video abstract

En el presente trabajo se exponen los resultados preliminares de la experiencia de implementación de un modelo de investigación-acción con un enfoque prospectivo empleando la estrategia de Ciencia Ciudadana, que tuvo por objetivo de generar información útil para el manejo comunitario de riesgos ambientales y la salud de las personas expuestas a agrotóxicos (glifosato, entre otros) como práctica común en la producción agrícola en las regiones lacustres de la Ciénega de Chapala y Pátzcuaro-Zirahuén, en Michoacán, México. Se plantearon recomendaciones preliminares que dimensionan el problema y señalan potenciales líneas de investigación y educación para el manejo del riesgo y las vulnerabilidades; ya que el riesgo disminuye o aumenta en función del grado de conocimiento que sustenta las prácticas agrícolas para el control de plagas.