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Background & Aims: Expression of P21, encoded by the CDKN1A gene, has been associated with fibrosis progression in steatotic liver disease (SLD); however, the underlying mechanisms remain unknown. In the present study, we investigated the function of CDKN1A in SLD. Methods: CDKN1A expression levels were evaluated in different patient cohorts with SLD, fibrosis, and advanced chronic liver disease (ACLD). Cdkn1a-/- and Cdkn1a+/+ mice were fed with either a Western diet (WD), a Lieber-DeCarli (LdC) diet plus multiple EtOH (ethanol) binges, or a DuAL diet (metabolic dysfunction-associated fatty liver disease and alcohol-related liver). Primary hepatocytes were isolated and functional assays performed. Results: A significant increase in CDKN1A expression was observed in patients with steatohepatitis and fibrosis (with a positive correlation with both NAFLD Activity Score and fibrosis staging scores), cirrhosis and ACLD. Cdkn1a+/+ mice, fed a DuAL diet exhibited liver injury and cell death increased reactive oxygen species (ROS), and markers of senescence (γH2AX, β-GAL, Cdkn1a/p53) contributing to steatosis and inflammation. In contrast, Cdkn1a-/- mutant mice showed a significant decrease in senescence-associated markers as well as in markers of liver injury, hepatic steatosis and an increase in fatty acid oxidation and reduction in free fatty acid uptake as well as de novo lipogenesis. Mechanistically, activation of the AMPK-SIRT3 was observed in Cdkn1a-deleted animals. Conclusions: Cdkn1a deletion protected against preclinical SLD by promoting fatty acid oxidation and preventing free fatty acid uptake and de novo lipogenesis via the AMPK-SIRT3 axis. CDKN1A expression was found to be directly correlated with increased severity of NAFLD Activity Score and fibrosis in patients with SLD. CDKN1A could be a potential theragnostic target for the treatment of metabolic dysregulation in patients with SLD, with and without alcohol consumption. Impact and implications:: Expression of p21, encoded by the CDKN1A gene, has been associated with fibrosis progression in steatotic liver disease (SLD), but the molecular mechanisms remain elusive. Interestingly, in this study we found that Cdkn1a deletion protected against preclinical SLD by promoting fatty acid oxidation and preventing free fatty acid uptake and de novo lipogenesis, via the AMPK-SIRT3 axis. Translationally, Cdkn1a expression was found to be directly correlated with increased severity of NAFLD Activity Score (NAS) and fibrosis in SLD patients, and therefore, CDKN1A might be used potential theragnostic target for the treatment of metabolically induced SLD, with and without alcohol consumption.

Parkinson’s disease is a pathology with a wide range of in vivo and in vitro models available. Among these, the SH-SY5Y neuroblastoma cell line is one of the most employed. This model expresses catecholaminergic markers and can differentiate and acquire various neuronal phenotypes. However, challenges persist, primarily concerning the variability of growth media, expression of dopaminergic markers, and a wide variety of differentiation protocols have been reported in the literature without direct comparison between them. This lack of standardized differentiation conditions impacts result reproducibility and it makes it very difficult to compare the results obtained from different research groups. An alternative cellular model is the neuroblastoma BE (2)-M17 which exhibits a high basal expression of numerous dopaminergic markers such as tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), and dopamine transporter (DAT). The BE (2)-M17 cells show neuronal properties, grows rapidly in conventional media, and can easily be differentiated to increase their dopaminergic phenotype. In this review, we will thoroughly explore the properties of the BE (2)-M17 cell line and discuss its potential as an excellent model for studying Parkinson’s disease.

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

The purpose of this work is to present an analytical method that allows to estimate in an approximate and fast way the presence of the non-resonant and ultra-fast multipactor effect in RF accelerating structures in the presence of high gradient electromagnetic fields. This single-surface multipactor regime, which has been little studied in the scientific literature, is characterised by appearing only under conditions of very strong RF electric fields (of the order of tens or hundreds of MV/m), where it is predominant over other types of single- or dual-surface resonance described in classical multipactor theory. This type of multipactor causes a rapid growth of the electron population and poses a serious drawback in the operation of RF accelerator components operating under high gradient conditions. Specifically, in dielectric-assist accelerating structures (DAA) it has been experimentally found that the presence of multipactor limits the maximum operating gradient of these components due to a significant increase in the reflected power due to the discharge, being this phenomenon the main problem to overcome. In a previous work, we found and described in detail by means of numerical simulations the presence of this non-resonant and ultra-fast multipactor regime in a DAA structure design for hadrontherapy. Here we aim to present a simple and fast method to predict the presence of this non-resonant and ultra-fast multipactor regime in RF accelerator structures with cylindrical revolution symmetry around the acceleration axis. This method is especially useful in the design stages of accelerating structures as it provides much faster results than numerical simulations of the multipactor, with quite good accuracy in a wide range of cases as shown in this paper.

Resumen: Introducción: la simulación como herramienta docente está en expansión en la educación de grado. El objetivo de este estudio es describir esta metodología aplicada al paciente pediátrico y descubrir las opiniones de los alumnos. Material y métodos: se realizaron 14 sesiones de simulación clínica avanzada (SCA) de pediatría a 168 alumnos de 6.° curso del grado de Medicina, con los escenarios de bronquiolitis, RCP, taquicardia supraventricular, crisis convulsiva y exploración de centro salud, durante los cursos 2020-2021 y 2021-2022. Tras la SCA tuvieron la oportunidad de responder a una encuesta de satisfacción de 29 preguntas. Resultados: 103/168 (61,3%) alumnos contestaron la encuesta de satisfacción. Las puntuaciones medias ± SD (sobre un máximo de 5) de los ítems principales fueron: aprendizaje de habilidades técnicas 4,58 ± 0,59; comunicación y motivación del alumno en la simulación clínica 4,94 ± 0,24. Sobre la estructura de la sesión de simulación, la puntuación media mejor valorada fue el profesorado 4,95 ± 0,26 y la duración del caso 4,75 ± 0,64. La valoración del alumno sobre el incremento de los conocimientos prácticos en pediatría fue elevada. Conclusiones: la SCA con práctica deliberada que sigue el método de aprendizaje por repetición, es considerada por los alumnos útil y motivadora para su formación. Al terminar la SCA, 87,4% de los participantes consideraron que se sentían capaces de enfrentarse a una urgencia pediátrica; 96% se sentía capaz de identificar a un enfermo inestable aplicando el triángulo de evaluación pediátrica; 94% sabría informar a los padres de forma clara y comprensible. Abstract: Introduction: Simulation as a teaching tool is expanding in healthcare disciplines and is being implemented in pediatric undergraduate education. This study describes this teaching methodology applied to pediatric patient knowledge and considers student opinions in order to tailor it to their educational needs. Methods: Fourteen sessions of advanced clinical simulation (ACS) in Pediatrics were conducted with 168 sixth-year medical students, featuring scenarios of bronchiolitis, CPR, supraventricular tachycardia, seizure, and primary care examination, during the academic years 2020-2021 and 2021-2022. After the ACS, the students were given the opportunity to respond to a satisfaction survey. Results: 103 out of 168 (61,3%) students completed the survey. The average scores ± SD (on a maximum of 5) for the main items were as follows: learning technical skills 4,58 ± 0,59; communication and student motivation in ACS 4,94 ± 0,24. Regarding the structure ACS session, the highest rated average score was for the faculty 4,95 ± 0,26, and the case duration 4,75 ± 0,64. The student assessment of increased practical knowledge in pediatrics was high. Conclusions: ACS with deliberate practice that follows a learning by repetition method is considered useful and motivational learning amongs students. Upon completion of the ACS, 87.4% of the participants felt capable of initially managing a pediatric emergency; 96% felt capable of identifying an unstable patient using the pediatric assessment triangle; and 94% stated that they would be able to provide clear and understandable information to parents.

El objetivo del artículo es describir el estado del desarrollo tecnológico y la cadena de valor eólica en México. Los resultados muestran que este país se ha enfocado en acumular capacidad instalada, mediante la importación de tecnología, desestimando el desarrollo de capacidades tecnológicas nacionales. Los hallazgos indican que esta política ha favorecido que las patentes sean desarrolladas por extranjeros y empresas privadas, siendo testimonial las patentes registradas en universidades nacionales. Su originalidad consiste en proponer una reconfiguración de la cadena de valor, que incluye actores para un desarrollo bajo el modelo de las cinco hélices.

Background: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study. Methods: First-line endocrine-sensitive, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) patients received palbociclib capsules plus fulvestrant or letrozole. The primary endpoint was progression-free survival (PFS). This post-hoc analysis compared PPI use. Patients were PPI-naïve (N-PPI) if not on PPI during the study, and either early (E-PPI) or long-term PPI (LT-PPI) if on PPI at study entry or for at least ≥⅔ of treatment, respectively. PPI groups were not mutually exclusive. Results: Among 486 patients, 66.9 % were N-PPI, 13.2 % E-PPI, 18.7 % LT-PPI, and 11.5 % of the PPI users were defined as neither. Median PFS (mPFS) was 29.6 months in the study population, 28.7 months in N-PPI, 23.0 months in E-PPI (Hazard Ratio [HR] 1.5; 95%Confidence Interval [CI] 1.1–2.2; p = 0.024), and 23.0 months in LT-PPI (HR 1.4; 95%CI 1.0–1.9; p = 0.035). By landmark analysis, PPI use was associated with poorer mPFS at 3 and 12 months. Grade ≥3 hematological adverse events occurred in 71.7 % of N-PPI, 57.8 % of E-PPI (p = 0.021), and 54.9 % of LT-PPI (p = 0.003). Dose reductions and dosing delays due to hematological toxicity occurred in 70.8 % of N-PPI, 56.3 % of E-PPI (p = 0.018), and 52.7 % of LT-PPI (p = 0.002). Conclusions: PPI use may reduce palbociclib capsule toxicity, dose modifications, and clinical activity in HR+/HER2- ABC.

Purpose: This article harmonizes the causal diagram with the objective tree to evaluate service quality and to identify action strategies that improve the quality of service in the hotel industry. Design/methodology/approach: In stage I, we obtained the quality perception records of 127 historical costumers, and 384 questionnaires. Subsequently, a causal diagram was generated in stage II. And finally, the above-mentioned strategies were created. The Causal Diagram clarifies the relationship between customer complaints and company weaknesses. Findings: The goal tree makes it possible to categorize these strategies according to target levels. Research limitations/implications: Costumers' opinions could generate biases in their responses. Future studies must consider other methods, such as Fuzzy Logic to reduce this bias. Practical and social implications: This study approach can be replicated in other industrial sectors and is particularly useful for defining improvement plans related to service quality. Originality/value: The integration of these tools will allow managers to better understand the experiences reported by guests because it allows understanding of the behaviors between the variables that influence the quality of service and the variables under the tangible elements of the service.

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

A phase 1–2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382), with parallel groups, involving 1161 participants, was designed to assess the safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in 55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe—no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headaches predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p < 0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

The success of using active restoration in Mediterranean-type climate zones mostly depends on an appropriate matching of plant species and specific management prescriptions upon establishment. In this study, we assessed the early growth and short-term physiological acclimation of seven common species found in the sclerophyllous forests in central Chile to water restriction and shading. We established a nursery experiment that included three treatments (T0: sun-exposed and water-restricted, T1: sun-exposed and fully irrigated, and T2: shaded and fully irrigated) and seven tree species differing in their shade and drought tolerance (Quillaja saponaria Molina, Aristotelia chilensis (Mol.) Stuntz, Peumus boldus Molina, Lithraea caustica (Mol.) Hook. and Arn, Luma apiculata (DC.) Burret, Colliguaja odorifera Molina, and Escallonia pulverulenta (Ruiz and Prav.) Pers). We measured the increment in seedling height and different leaf morpho-physiological traits during two months in the dry season. Based on the measured traits, none of the species took advantage of the higher water availability in T1 relative to T0, but most of the species responded to the shade in T2, regardless of their shade or drought tolerance. Height increments due to shade varied from 0% in P. boldus to 203% in L. apiculata. Overall, all the species responded similarly to the treatments in specific leaf area, chlorophyll content index, photosynthetic rate, stomatal conductance, and intrinsic water use efficiency. This suggests that the species exhibited similar acclimation patterns of these parameters to shade and drought, even regarding the variation in midday xylem water potential found in the water-restricted treatment T0 (from −1.5 MPa in P. boldus to −3.1 MPa in E. pulverulenta). In this study, shading had a higher positive effect on the seedling performance of sclerophyllous species than watering, which at operational level highlights the need for investing in tree shelters when using these species in restoration programs.

Abstract Progressive hepatic damage and fibrosis are major features of chronic liver diseases of different etiology, yet the underlying molecular mechanisms remain to be fully defined. N-RAS, a member of the RAS family of small guanine nucleotide-binding proteins also encompassing the highly homologous H-RAS and K-RAS isoforms, was previously reported to modulate cell death and renal fibrosis; however, its role in liver damage and fibrogenesis remains unknown. Here, we approached this question by using N-RAS deficient (N-RAS−/−) mice and two experimental models of liver injury and fibrosis, namely carbon tetrachloride (CCl4) intoxication and bile duct ligation (BDL). In wild-type (N-RAS+/+) mice both hepatotoxic procedures augmented N-RAS expression in the liver. Compared to N-RAS+/+ counterparts, N-RAS−/− mice subjected to either CCl4 or BDL showed exacerbated liver injury and fibrosis, which was associated with enhanced hepatic stellate cell (HSC) activation and leukocyte infiltration in the damaged liver. At the molecular level, after CCl4 or BDL, N-RAS−/− livers exhibited augmented expression of necroptotic death markers along with JNK1/2 hyperactivation. In line with this, N-RAS ablation in a human hepatocytic cell line resulted in enhanced activation of JNK and necroptosis mediators in response to cell death stimuli. Of note, loss of hepatic N-RAS expression was characteristic of chronic liver disease patients with fibrosis. Collectively, our study unveils a novel role for N-RAS as a negative controller of the progression of liver injury and fibrogenesis, by critically downregulating signaling pathways leading to hepatocyte necroptosis. Furthermore, it suggests that N-RAS may be of potential clinical value as prognostic biomarker of progressive fibrotic liver damage, or as a novel therapeutic target for the treatment of chronic liver disease.

Abstract One of the major challenges currently faced by global health systems is the prolonged COVID-19 syndrome (also known as “long COVID”) which has emerged as a consequence of the SARS-CoV-2 epidemic. It is estimated that at least 30% of patients who have had COVID-19 will develop long COVID. In this study, our goal was to assess the plasma metabolome in a total of 100 samples collected from healthy controls, COVID-19 patients, and long COVID patients recruited in Mexico between 2020 and 2022. A targeted metabolomics approach using a combination of LC–MS/MS and FIA MS/MS was performed to quantify 108 metabolites. IL-17 and leptin were measured in long COVID patients by immunoenzymatic assay. The comparison of paired COVID-19/long COVID-19 samples revealed 53 metabolites that were statistically different. Compared to controls, 27 metabolites remained dysregulated even after two years. Post-COVID-19 patients displayed a heterogeneous metabolic profile. Lactic acid, lactate/pyruvate ratio, ornithine/citrulline ratio, and arginine were identified as the most relevant metabolites for distinguishing patients with more complicated long COVID evolution. Additionally, IL-17 levels were significantly increased in these patients. Mitochondrial dysfunction, redox state imbalance, impaired energy metabolism, and chronic immune dysregulation are likely to be the main hallmarks of long COVID even two years after acute COVID-19 infection.

Climate action plans under the Paris Climate Agreement and other national commitments aimed at improving soil-based ecosystem services require the operational monitoring of soil carbon (C). The European Union is aiming to enhance soil health, and as part of the proposed Soil Monitoring Law, the European Commission recommends the monitoring of the soil C loss indicator among other soil health indicators. In this study, we evaluate the feasibility of the proposed soil C loss indicator by assessing its performance using the EU-wide 2009 LUCAS soil survey data. The proposed indicator is the soil organic carbon (SOC) to clay ratio, with a threshold value of 1:13. The results are also compared with the C stock changes reported by countries to the climate convention (UNFCCC). Our results reveal that the variation in SOC and clay content at European scale exceeds that of the data used to develop the proposed indicator. We also found that the variation in the SOC content was influenced not only by clay content but also by climate and land-use reflecting C input levels. Therefore, the defined threshold is inadequate for detecting degraded soils if the SOC and clay content are beyond the conditions used to establish the criteria. Furthermore, major discrepancies were observed between the soil carbon stock changes reported by the national greenhouse gas (GHG) inventories and the proportions of degraded soils identified by using the soil C loss indicator. We conclude that employing a single indicator such as SOC:Clay ratio with one threshold value for all soils across various land covers, management practices, and climatic conditions, as defined by the European Commission for the Soil Monitoring Law, is inappropriate for monitoring soil C loss.

BackgroundAlcohol misuse, binge drinking pattern, and gender-specific effects in the middle-aged population has been clearly underestimated. In the present study, we focused on understanding gender-specific effects of alcohol exposure on the gut-liver axis and the role of gut microbiota in modulating gender-specific responses to alcohol consumption.MethodsFifty-two-week-old female and male C57BL/6 mice were fasted for 12 h, and then administered a single oral dose of ethanol (EtOH) (6 g/kg). Controls were given a single dose of PBS. Animals were sacrificed 8 h later. Alternatively, fecal microbiota transplantation (FMT) was performed in 52-week-old male mice from female donors of the same age. Permeability of the large intestine (colon), gut microbiota, liver injury, and inflammation was thoroughly evaluated in all groups.ResultsMiddle-aged male mice exposed to EtOH showed a significant increase in gut permeability in the large intestine, evaluated by FITC-dextran assay and ZO-1, OCCLUDIN and MUCIN-2 immuno-staining, compared to PBS-treated animals, whilst female mice of the same age also increased their gut permeability, but displayed a partially maintained intestinal barrier integrity. Moreover, there was a significant up-regulation of TLRs and markers of hepatocellular injury, cell death (AST, TUNEL-positive cells) and lipid accumulation (ORO) in male mice after EtOH exposure. Interestingly, FMT from female donors to male mice reduced gut leakiness, modified gut microbiota composition, ameliorated liver injury and inflammation, TLR activation and the senescence phenotype of middle-aged mice.ConclusionOur findings highlighted the relevance of gender in middle-aged individuals who are exposed to alcohol in the gut-liver axis. Moreover, our study revealed that gender-specific microbiota transplantation might be a plausible therapy in the management of alcohol-related disorders during aging.

We present CiftiStorm, an electrophysiological source imaging (ESI) pipeline incorporating recently developed methods to improve forward and inverse solutions. The CiftiStorm pipeline produces Human Connectome Project (HCP) and megconnectome-compliant outputs from dataset inputs with varying degrees of spatial resolution. The input data can range from low-sensor-density electroencephalogram (EEG) or magnetoencephalogram (MEG) recordings without structural magnetic resonance imaging (sMRI) to high-density EEG/MEG recordings with an HCP multimodal sMRI compliant protocol. CiftiStorm introduces a numerical quality control of the lead field and geometrical corrections to the head and source models for forward modeling. For the inverse modeling, we present a Bayesian estimation of the cross-spectrum of sources based on multiple priors. We facilitate ESI in the T1w/FSAverage32k high-resolution space obtained from individual sMRI. We validate this feature by comparing CiftiStorm outputs for EEG and MRI data from the Cuban Human Brain Mapping Project (CHBMP) acquired with technologies a decade before the HCP MEG and MRI standardized dataset.

The digital transformation of urban transportation systems remains a critical challenge in Smart Cities' development. This paper addresses the pervasive issue of inadequate digitalization within public transportation systems. The paper highlights the promise of Account Based Ticketing (ABT) as a pivotal solution for integrating diverse public and private transportation modes allowing users to access different transportation services with a single account, without the need for new physical tickets or cards. ABT approach represents a breakthrough in seamlessly amalgamating various transportation operators' systems, transcending city limits into broader metropolitan spheres, and fostering integration and interoperability across transportation modes operated by disparate entities. Emphasizing beyond-city-scale integration, it explores the potential value of ABT to connect transportation networks extending into metropolitan influences. The proposed approach involves analyzing the implementation and functionality of ABT systems, underlining their capacity to overcome existing barriers in multi-modal transportation. The results anticipate enhanced accessibility, increased ridership, and streamlined user experiences, contributing to the realization of efficient and interconnected urban transport networks. This study not only underscores the value of ABT in revolutionizing contemporary transportation systems but also examines its broader implications for future urban planning and smart city development, highlighting the transformative potential and essential role that ABT plays in shaping the future of integrated transportation and Mobility as a Service in Smart Cities.

Dielectric Assist Accelerating (DAA) structures based on ultralow-loss ceramic are being studied as an alternative to conventional disk-loaded copper cavities. This accelerating structure consists of dielectric disks with irises arranged periodically in metallic structures working under the TM02-π mode. In this paper, the numerical design of an S-band DAA structure for low beta particles, such as protons or carbon ions used for Hadrontherapy treatments, is shown. Four dielectric materials with different permittivity and loss tangent are studied as well as different particle velocities. Through optimization, a design that concentrates most of the RF power in the vacuum space near the beam axis is obtained, leading to a significant reduction of power loss on the metallic walls. This allows to fabricate cavities with an extremely high quality factor, over 100,000, and shunt impedance over 300 MΩ/m at room temperature. During the numerical study, the design optimization has been improved by adjusting some of the cell parameters in order to both increase the shunt impedance and reduce the peak electric field in certain locations of the cavity, which can lead to instabilities in its normal functioning.

El objetivo del presente trabajo fue evaluar el desempeño de una red de distribución de agua potable. Los datos se obtuvieron por medio del personal del sistema de aguas del municipio en estudio. Se emplearon métricas de capacidad Six Sigma para evaluar su desempeño mediante la simulación con el software EPANET. De acuerdo con los resultados, el sistema estudiado no cumple con los requerimientos de los usuarios. El desabastecimiento de agua no se debe a la falta de extracción, sino a las pérdidas que ocurren en el sistema, que pueden alcanzar hasta el 43 %. Se comparó el desempeño actual con el obtenido al inducir cambio en la simulación. El desempeño de la red puede ser mejorado con cambios en algunas condiciones de bombeo, distribución; además, la red requiere revisión y mantenimiento para evitar la pérdida de agua. Incrementar la extracción ocultaría el problema de desperdicio y generaría sobreexplotación de los pozos.

Purpose: Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival. Methods: We enrolled 220 patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6 polymorphisms were determined, and the phenotype was estimated according to the Clinical Pharmacogenetics Implementation Consortium. Disease-free survival (DFS) and overall survival (OS) were analysed considering the entire patient group, and a subgroup of 110 patients selected by Propensity Score Matching (PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4 months and 60 mg/day for 4 months before returning to the standard dose of 20 mg/day until completing 5 years of treatment. Results: The analysis of the influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup revealed no significant differences for DFS or OS. Furthermore, DFS and OS were analysed in relation to various covariates such as age, histological grade, nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only age, histological grade, nodal status, and chemotherapy treatment demonstrated statistical significance. Conclusion: An early increase in tamoxifen dose in PM patients is not associated with survival differences among CYP2D6 phenotypes.

Life Cycle Assessment (LCA) is normally used independently of the physical and temporal location of the product, process or service under analysis. This makes LCA results more easily comparable and globally accepted. At the same time, it has drawbacks though, e.g. land use will have the same impact regardless of location. However, the use of certain terrains in high erosion risk areas as compared to others in low erosion risk areas will have a different impact on the ecosystem. The availability of airborne Light Detection and Ranging (LiDAR) data (ALS) allows a quick and accurate morphogeometric analysis of any terrain. For this reason, this article offers a methodology, based on Revised Universal Soil Loss Equation (RUSLE) method and airborne LiDAR data, for the straightforward detection of zones with high vulnerability to erosion problems. Based on these local erosion risk data, a method is developed to assess the environmental impact of land use, based on its location. In this way, the LCA methodology is incorporated to gather local data, dependent on the specific location of the activity under analysis. The methodology developed has been applied, as a case study, to a specific municipality in the high mountains of the Autonomous Community of La Rioja (Spain).

Hospitals have demonstrated their enormous capacity to adapt to the rapidly changing situation imposed by the pandemic: increasing the number of intensive care units and intermediate and inpatient beds, with the corresponding human resources, services and facilities required. Internationally, the enormous demand to manage the COVID-19 pandemic has challenged hospitals in terms of staffing, supplies and equipment. This article analyses the effect of the COVID-19 pandemic on hospital activities, from the perspective of its environmental impact. It compares a year of normal hospital activities, 2019, with data on hospital activities from 2020. The aim of this research is to analyse the changes produced by the pandemic in the regular activities of the hospital and to determine the environmental impact, which allows reflecting on the exceptional situation generated. The results show that the hospital’s environmental impact increased significantly in 2020 compared to 2019, with a 17.2% increase in overall environmental efficiency indices. The main contributors to this increase were waste generation and medical gas consumption, which are critical aspects of hospital activities during the pandemic.

The objective of this work is the evaluation of the risk of suffering a multipactor discharge in an S-band dielectric-assist accelerating (DAA) structure for a compact low-energy linear particle accelerator dedicated to hadrontherapy treatments. A DAA structure consists of ultra-low loss dielectric cylinders and disks with irises which are periodically arranged in a metallic enclosure, with the advantage of having an extremely high quality factor and very high shunt impedance at room temperature, and it is therefore proposed as a potential alternative to conventional disk-loaded copper structures. However, it has been observed that these structures suffer from multipactor discharges. In fact, multipactor is one of the main problems of these devices, as it limits the maximum accelerating gradient. Because of this, the analysis of multipactor risk in the early design steps of DAA cavities is crucial to ensure the correct performance of the device after fabrication. In this paper, we present a comprehensive and detailed study of multipactor in our DAA design through numerical simulations performed with an in-house developed code based on the Monte–Carlo method. The phenomenology of the multipactor (resonant electron trajectories, electron flight time between impacts, etc.) is described in detail for different values of the accelerating gradient. It has been found that in these structures an ultra-fast non-resonant multipactor appears, which is different from the types of multipactor theoretically studied in the scientific literature. In addition, the effect of several low electron emission coatings on the multipactor threshold is investigated. Furthermore, a novel design based on the modification of the DAA cell geometry for multipactor mitigation is introduced, which shows a significant increase in the accelerating gradient handling capabilities of our prototype.

Abstract Nanotechnology is one of the most important and relevant disciplines today due to the specific electrical, optical, magnetic, chemical, mechanical and biomedical properties of nanoparticles. In the present study we demonstrate the efficacy of Cuphea procumbens to biogenerate silver nanoparticles (AgNPs) with antibacterial and antitumor activity. These nanoparticles were synthesized using the aqueous extract of C. procumbens as reducing agent and silver nitrate as oxidizing agent. The Transmission Electron Microscopy demonstrated that the biogenic AgNPs were predominantly quasi-spherical with an average particle size of 23.45 nm. The surface plasmonic resonance was analyzed by ultraviolet visible spectroscopy (UV–Vis) observing a maximum absorption band at 441 nm and Infrared Spectroscopy (FT IR) was used in order to structurally identify the functional groups of some compounds involved in the formation of nanoparticles. The AgNPs demonstrated to have antibacterial activity against the pathogenic bacteria Escherichia coli and Staphylococcus aureus, identifying the maximum zone of inhibition at the concentration of 0.225 and 0.158 µg/mL respectively. Moreover, compared to the extract, AgNPs exhibited better antitumor activity and higher therapeutic index (TI) against several tumor cell lines such as human breast carcinoma MCF-7 (IC50 of 2.56 µg/mL, TI of 27.65 µg/mL), MDA-MB-468 (IC50 of 2.25 µg/mL, TI of 31.53 µg/mL), human colon carcinoma HCT-116 (IC50 of 1.38 µg/mL, TI of 51.07 µg/mL) and melanoma A-375 (IC50 of 6.51 µg/mL, TI of 10.89 µg/mL). This fact is of great since it will reduce the side effects derived from the treatment. In addition, AgNPs revealed to have a photocatalytic activity of the dyes congo red (10–3 M) in 5 min and malachite green (10–3 M) in 7 min. Additionally, the degradation percentages were obtained, which were 86.61% for congo red and 82.11% for malachite green. Overall, our results demonstrated for the first time that C. procumbens biogenerated nanoparticles are excellent candidates for several biomedical and environmental applications.

The Subtropical Mountain Forests or Yungas at the northern extreme of Argentina (Sierras de Tartagal, Alto Macueta and del Alto Río Seco, Salta Province) were bioclimatically characterized for the first time. In this study, the methodology of the Bioclimatic Classification of Earth was applied. Twelve Temperature and Precipitation climatic parameters were used and three bioclimatic indices corresponding to 54 Bioclimatic Reference Localities (BRL) established in the study area were also calculated. From them we determined the bioclimatic units of each BRL at the level of Macrobioclimate, Bioclimate, Thermotypes and Ombrotypes. Subsequently, three bioclimatic maps (Bioclimate, Thermotypes and Ombrotypes) and two bioclimatic distribution maps of the forests and its vegetation belt (Premontane Forest and Montane Rainforest) were digitally developed using the QGIS software. The results obtained show that these forests are distributed within the Tropical Macrobioclimate and Tropical Pluviseasonal Bioclimate, with Upper Thermotropical and Lower Mesotropical thermotypes and Lower Subhumid and Upper Subhumid ombrotypes. The lowest vegetation belt, the Premontane Forest, is distributed between (≈400) 429-889 (≈900) m asl and exhibits two thermal variants: the warm Thermotropical Premontane Forest and the more temperate Mesotropical Premontane Forest. The Montane Rainforest is distributed at higher altitudes between (≈900) 965-1178 (≈1200) m als under Lower Mesotropical Thermotype. Both vegetation belts present two ombric variants, whose geographic distribution is determined by the precipitation gradient operating in the region: towards the West, the more humid variants are distributed under the Upper Subhumid ombrotype, while towards the East, the less humid variants are found under Lower Subhumid ombrotype. The present work constitutes the first bioclimatic study carried out in this forest formation applying the methodology of the Bioclimatic Classification of the Earth. It also lays the foundations and contributes whith valuable information to future floristic, vegetational, ecological and biogeographical studies and those focused on the conservation and sustainable management of native forests at the northern extreme of Argentina.

Neurodegenerative diseases (ND) are undoubtedly part of the more important health issues worldwide. The loss of independence and decreased quality of life are characteristics of these patients that translate into an economic load on relatives and health services. Although myriad factors or metabolic alterations are blamed as causatives, there is a common defect in almost every ND, mitochondrial dysfunction. Mitochondria are the cell’s leading energy supplier; therefore, altering its function will affect the cellular function with the energy demand. Defects in mitochondrial mechanisms such as ATP synthesis by the mitochondrial respiratory chain, mitochondrial dynamics, apoptosis regulation, and oxidative stress are described as part of the pathological characteristics of Alzheimer’s, Parkinson’s, Huntington’s diseases, and Amyotrophic Lateral Sclerosis. In this review, we will briefly describe the mitochondrial roles in cell life before analyzing the recently published bibliography that addresses the mitochondrial dysfunction and mitochondrial mechanisms implicated in ND and will discuss a relevant question in the field: is mitochondrial dysfunction a cause or consequence for these diseases?

Chimeric antigen receptor (CAR)-T cell therapy has proven to be a powerful treatment for hematological malignancies. The situation is very different in the case of solid tumors, for which no CAR-T-based therapy has yet been approved. There are many factors contributing to the absence of response in solid tumors to CAR-T cells, such as the immunosuppressive tumor microenvironment (TME), T cell exhaustion, or the lack of suitable antigen targets, which should have a stable and specific expression on tumor cells. Strategies being developed to improve CAR-T-based therapy for solid tumors include the use of new-generation CARs such as TRUCKs or bi-specific CARs, the combination of CAR therapy with chemo- or radiotherapy, the use of checkpoint inhibitors, and the use of oncolytic viruses. Furthermore, despite the scarcity of targets, a growing number of phase I/II clinical trials are exploring new solid-tumor-associated antigens. Most of these antigens are of a protein nature; however, there is a clear potential in identifying carbohydrate-type antigens associated with tumors, or carbohydrate and proteoglycan antigens that emerge because of aberrant glycosylations occurring in the context of tumor transformation.

RESUMEN Introducción y objetivos: Durante el confinamiento por la pandemia provocada por el coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2) se observó un descenso en los ingresos por síndrome coronario agudo (SCA). El objetivo de este estudio fue evaluar el impacto del confinamiento en la incidencia, la morbimortalidad y el manejo del SCA. Métodos: Estudio retrospectivo y multicéntrico, en el que se incluyeron los pacientes ingresados por SCA entre el 14 de febrero y el 24 de junio de 2020. Se excluyeron los pacientes con infarto agudo de miocardio y coronarias sin lesiones significativas. Se establecieron 3 grupos en función del periodo de ingreso: a) 1 mes antes del confinamiento; b) durante el confinamiento; y c) 1 mes después del confinamiento. Se evaluaron las diferencias en la mortalidad entre los 3 grupos, así como las diferencias temporales entre el inicio de los síntomas y el primer contacto médico. Resultados: Se incluyeron 634 pacientes (grupo A: 205; grupo B: 303; grupo C: 126). Se observó un descenso del 41% en los ingresos por SCA durante el primer mes del confinamiento respecto al mes previo, así como un retraso en el diagnóstico durante este mismo periodo: grupo A, 66 minutos (45-180); grupo B, 120 minutos (60-240); grupo C, 120 minutos (60-240) (p = 0,007). Sin embargo, no hubo mayor mortalidad durante el confinamiento (riesgo relativo, 1.26; intervalo de confianza del 95%, 0.53-2.97; p = 0,60). Conclusiones: Durante el confinamiento se produjo un marcado descenso en los ingresos por SCA y, a pesar de que se dilató el tiempo desde el inicio de los síntomas hasta el primer contacto médico en este periodo en los pacientes con SCA con elevación del segmento ST, la mortalidad fue similar en los 3 grupos estudiados.

ABSTRACT Introduction and objectives: During the lockdown due to the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a decrease in the number of admissions due to acute coronary syndrome (ACS) was observed. The objective of our study was to evaluate the impact lockdown had on the incidence, morbidity and mortality, and management of ACS. Methods: A retrospective and multicenter study was conducted including patients admitted due to ACS from February 14 through June 24, 2020. Patients with acute myocardial infarction and coronary arteries without significant lesions were excluded. The following groups were established based on the period of admission: a) 1 month before lockdown; b) during lockdown; and c) 1 month after lockdown. The differences in mortality seen among the 3 groups were evaluated, as well as the temporal differences reported between symptom onset and the first medical contact (FMC). Results: a total of 634 patients were included (group a, 205; group b, 303, and group c, 126). A 41% decrease in the number of admissions due to ACS was observed during the first month of lockdown compared to the previous month, as well as diagnostic delay during this same period (group a, 66 minutes (45-180), group b, 120 minutes (60-240), and group c, 120 minutes (60-240), P = .007). However, a higher mortality rate during confinement was not reported (RR, 1.26; 95%CI, 0.53-2.97; P = .60). Conclusions: During lockdown, a remarkable decrease in the number of admissions due to ACS was observed, and although there was an increase in the time elapsed from symptom onset to the FCM in this period in patients with STEMI, the mortality rate was similar in the 3 groups studied.

IntroductionThe Unfolded Protein Response, a mechanism triggered by the cell in response to Endoplasmic reticulum stress, is linked to inflammatory responses. Our aim was to identify novel Unfolded Protein Response-mechanisms that might be involved in triggering or perpetuating the inflammatory response carried out by the Intestinal Epithelial Cells in the context of Inflammatory Bowel Disease.MethodsWe analyzed the transcriptional profile of human Intestinal Epithelial Cell lines treated with an Endoplasmic Reticulum stress inducer (thapsigargin) and/or proinflammatory stimuli. Several genes were further analyzed in colonic biopsies from Ulcerative Colitis patients and healthy controls. Lastly, we generated Caco-2 cells lacking HMGCS2 by CRISPR Cas-9 and analyzed the functional implications of its absence in Intestinal Epithelial Cells.ResultsExposure to a TLR ligand after thapsigargin treatment resulted in a powerful synergistic modulation of gene expression, which led us to identify new genes and pathways that could be involved in inflammatory responses linked to the Unfolded Protein Response. Key differentially expressed genes in the array also exhibited transcriptional alterations in colonic biopsies from active Ulcerative Colitis patients, including NKG2D ligands and the enzyme HMGCS2. Moreover, functional studies showed altered metabolic responses and epithelial barrier integrity in HMGCS2 deficient cell lines.ConclusionWe have identified new genes and pathways that are regulated by the Unfolded Protein Response in the context of Inflammatory Bowel Disease including HMGCS2, a gene involved in the metabolism of Short Chain Fatty Acids that may have an important role in intestinal inflammation linked to Endoplasmic Reticulum stress and the resolution of the epithelial damage.

Abstract Background Leptin exerts both protective and deleterious effects on the heart; the first occurs under hypoxia- or ischemia-associated damage, the second is a pro-hypertrophic factor on cardiomyocytes. Therefore, leptin could represent a link between obesity and cardiovascular diseases. The study aimed to investigate the effect of leptin—the same concentration that is frequently measured in obesity and induces cardiac hypertrophy—on murine hearts following an episode of ischemia–reperfusion; moreover, we evaluated the heart's performance, hypertrophy, and activation of apoptosis. Rat hearts were perfused continuously with or without 3.1 nM leptin for one h before and 1 h after an episode of ischemia. Cardiac performance was evaluated, homogenates and mitochondria were prepared for western blot analysis of cardiac actin, leptin receptor, STAT3, pSTAT3, and apoptosis-related proteins Bax, Bcl-2, cytochrome c, and caspase 3. Results Leptin worsened heart recovery after ischemia (p

La pandemia por Covid-19 ha traído cambios y consecuen-cias económicas a empresas de diferentes industrias a ni-vel mundial, de ahí la importancia de analizar y evaluar las afectaciones económicas-fi nancieras resultantes de la pan-demia. La siguiente investigación se centra en la industria del comercio electrónico y las afectaciones económicas sufridas en este sector en determinadas variables como lo son las ventas, la captación bursátil, razón de rentabilidad del patrimonio, razón de endeudamiento y razón de renta-bilidad sobre activos, impulsadas por la situación sanitaria provocada por el virus SARS-CoV-2. En consecuencia, se uti-liza como fuente de información los estados fi nancieros e indicadores bursátiles de las empresas de Amazon, Merca-do Libre y Shopify, con el fi n de tener un panorama al sector estudiado a través de estos índices. En este sentido, y como resultado de la recolección y el análisis de datos se encontró que la industria del comercio electrónico aumentó sus ventas en el periodo 2018-2019 en un 20.81%, y para el periodo 2019-2020 se registró un in-cremento de un 38.18%, lo que supone una diferencia de 17 puntos porcentuales. Del mismo modo, la captación bursá-til creció de un 29.79% en el periodo 2018-2019, a un 87.24% en el periodo 2019-2020, lo que representa un incremento de 57 puntos porcentuales, quedando en evidencia la afec-tación económica positiva en el sector del comercio elec-trónico derivado de los cambios e innovaciones nacientes por el contexto sanitario en la que se desenvolvieron men-cionadas empresas.

Abstract Acetaminophen (APAP) hepatotoxicity induces endoplasmic reticulum (ER) stress which triggers the unfolded protein response (UPR) in hepatocytes. However, the mechanisms underlying ER stress remain poorly understood, thus reducing the options for exploring new pharmacological therapies for patients with hyperacute liver injury. Eight-to-twelve-week-old C57BL/6J Xbp1-floxed (Xbp1 f/f ) and hepatocyte-specific knockout Xbp1 mice (Xbp1 ∆hepa ) were challenged with either high dose APAP [500 mg/kg] and sacrificed at early (1–2 h) and late (24 h) stages of hepatotoxicity. Histopathological examination of livers, immunofluorescence and immunohistochemistry, Western blot, real time (RT)-qPCR studies and transmission electron microscopy (TEM) were performed. Pharmacological inhibition of XBP1 using pre-treatment with STF-083010 [STF, 75 mg/kg] and autophagy induction with Rapamycin [RAPA, 8 mg/kg] or blockade with Chloroquine [CQ, 60 mg/kg] was also undertaken in vivo. Cytoplasmic expression of XBP1 coincided with severity of human and murine hyperacute liver injury. Transcriptional and translational activation of the UPR and sustained activation of JNK1/2 were major events in APAP hepatotoxicity, both in a human hepatocytic cell line and in a preclinical model. Xbp1 ∆hepa livers showed decreased UPR and JNK1/2 activation but enhanced autophagy in response to high dose APAP. Additionally, blockade of XBP1 splicing by STF, mitigated APAP-induced liver injury and without non-specific off-target effects (e.g., CYP2E1 activity). Furthermore, enhanced autophagy might be responsible for modulating CYP2E1 activity in Xbp1 ∆hepa animals. Genetic and pharmacological inhibition of Xbp1 specifically in hepatocytes ameliorated APAP-induced liver injury by enhancing autophagy and decreasing CYP2E1 expression. These findings provide the basis for the therapeutic restoration of ER stress and/or induction of autophagy in patients with hyperacute liver injury.

Land management practices can have an impact on the environmental quality of soil and contribute to identifying the source of its pollution. The objective of this study was to determine presence of metallic and non-metallic elements as indicators of land use impact (livestock management, restoration strategies and without management practices) in the Monte Caldera communal lands located in Cerro de San Pedro, San Luis Potosi, Mexico. Eighteen samples were collected at depths of 0-10 cm and 10-20 cm for each land use. Total concentrations of Zr, Sr, U, Th, Pb, As, Rb, Cr, V, Ti, Zn, and Cu were determined by X-ray fluorescence. Mean concentrations ranged in the following order: Ti>Zr>Rb>V>Sr>Zn>Cr>Pb> Cu>Th>U>As, with concentrations for Ti, Cr, Th, U and As exceeding technical reference values for phytotoxic soils. Significant differences were evidenced by ANOVA between land use (Th, Pb, Rb, Cu) and soil depth (U, Pb, and As). Land use practices associated with restoration resulted in a positive environmental impact. These findings underscore the need to conduct follow-up studies in the area and further examine the relationship of such practices with other environmental factors. Highlights: • Soil management practices can affect the environmental quality of this resource and help diagnose the source of its contamination. • It is necessary to evaluate the Impact of land use on livestock management, restoration strategies, and without management or conservation areas. • By X-ray fluorescence technique the total concentration of Zr, Sr, U, Th, Pb, As, Rb, Cr, V, Ti, Zn, and Cu was determined. • Ti, Cr, Th, U and As exceed the technical reference values for consideration as phytotoxic in soils. • Land use associated with reclamation practices is an indicator of a positive influence on improving soil quality.

En este trabajo se describen algunos rasgos fenotípicos, ecológicos y etológicos de las gaviotas patiamarillas que se reproducen en el embalse del Ebro (norte de España) con el objetivo principal de evaluar el origen de esta población de reciente colonización. Para ello (1) se capturaron y midieron adultos, cuyas medidas corporales se compararon con las de una población atlántica y otra mediterránea, ambas tomadas de la bibliografía, (2) se midió el tamaño de los huevos, comparándolo con los de diferentes colonias atlánticas y mediterráneas, (3) se censó la colonia y evaluó la fenología de su reproducción (4) se anillaron adultos y pollos para conocer sus desplazamientos y compararlos con los de dos colonias atlánticas (5) se censó mensualmente la población presente en el embalse, de agosto a marzo. Se concluye que la población estudiada tiene algunas características morfológicas que la asemejan a las poblaciones atlánticas y otras a las que ocupan el litoral mediterráneo. No obstante, el tamaño de sus huevos, su fenología reproductora y su comportamiento migrador indican un probable origen mediterráneo. ABSTRACT: Since the middle of the 20th century, the yellow-legged gull has expanded its distribution and colonised the inland waters of Central Europe, France and the Iberian Peninsula. We describe here a number of phenotypic, ecological and ethological traits of the yellow-legged gulls breeding in the Ebro reservoir (northern Spain) with the main objective of evaluating the origin of this recently colonised population. For this purpose (1), adults were captured and body measurements were compared with those of an Atlantic and a Mediterranean population found in the literature, (2) the size of the eggs was measured, comparing this with those of different Atlantic and Mediterranean colonies, (3) the colony was counted and the phenology of its reproduction was evaluated (4) adults and chicks were ringed to know their movements and compare them with those of two Atlantic colonies, (5) the population present in the reservoir was counted on a monthly basis, between August and March. We conclude that the studied population has a number of phenotypic characteristics that differentiate this from both Atlantic and the Mediterranean gulls. However, the size of their eggs, their reproductive phenology and migratory behaviour indicate a probable Mediterranean origin.

BackgroundImmunocompromised patients have an increased risk of developing severe COVID disease, as well as a tendency to suboptimal responses to vaccines. The objective of this study was to evaluate the specific cellular and humoral adaptive immune responses of a cohort of kidney transplant recipients (KTR) after 3 doses of mRNA-1273 vaccine and to determinate the main factors involved.MethodsProspective observational study in 221 KTR (149 non infected), 55 healthy volunteers (HV) and 23 dialysis patients (DP). We evaluated anti-spike (by quantitative chemiluminescence immunoassay) and anti-nucleocapsid IgG (ELISA), percentage of TCD4+ and TCD8+ lymphocytes producing IFNγ against S-protein by intracellular flow cytometry after Spike-specific 15-mer peptide stimulation and serum neutralizing activity (competitive ELISA) at baseline and after vaccination.ResultsAmong COVID-19 naïve KTR, 54.2% developed cellular and humoral response after the third dose (vs 100% in DP and 91.7% in HV), 18% only showed cell-mediated response, 22.2% exclusively antibody response and 5.6% none. A correlation of neutralizing activity with both the IgG titer (r=0.485, p1000/mm3 [4.68 (1.72-12.73, p=0.003], eGFR>30 mL/min [7.34(2.72-19.84), p

El Programa Nacional Forestal busca promover la conservación, el manejo sustentable y la restauración. Este trabajo evalúa, bajo los enfoques socioeconómico y ecológico, los efectos del programa en dos ejidos en Calakmul, para generar recomendaciones que mejoren su gestión e implementación. La evaluación muestra que no se cumplen los objetivos para los que fue diseñado, ya que las condiciones socioeconómicas de la población objetivo no mejoraron y las áreas reforestadas presentaron niveles de sobrevivencia menores a 6%. Se sugiere mejorar la capacitación y el proceso de monitoreo o evaluación y adecuar las técnicas a las condiciones ambientales de cada región.

Abstract Drought-induced water stress affects the productivity of the Vanilla planifolia Jacks. ex Andrews crop. In vitro culture technique is an effective tool for the study of water stress tolerance mechanisms. This study aimed to evaluate the morphological, physiological and biochemical response of V. planifolia under in vitro water stress conditions induced with polyethylene glycol (PEG). In vitro regenerated shoots of 2 cm in length were subjected to different concentrations of PEG 6000 (0, 1, 2 and 3% w/v) using Murashige and Skoog semi-solid culture medium. At 60 days of culture, different growth variables, dry matter (DM) content, chlorophyll (Chl), soluble proteins (SP), proline (Pro), glycine betaine (GB), stomatal index (SI) and open stomata (%) were evaluated. Results showed a reduction in growth, Chl content, SP, SI and open stomata (%) with increasing PEG concentration, whereas DM, Pro and GB contents rose with increasing PEG concentration. In conclusion, PEG-induced osmotic stress allowed describing physiological and biochemical mechanisms of response to water stress. Furthermore, the determination of compatible Pro and GB osmolytes can be used as biochemical markers in future breeding programs for the early selection of water stress tolerant genotypes.

Nucleation of domains and domain walls by means of ultrashort laser pulses, and their current-driven shifting along a ferrimagnetic strip with high perpendicular magnetic anisotropy on top of a heavy metal, are both explored here by means of advanced micromagnetic modeling. Our results indicate that these systems are ideal candidates to develop high-density and high-efficient domain wall-based memory devices where the information is coded in series of bits in the form of perpendicular up and down domains flanked by chiral domain walls.

This study aimed to determine the presence of metal elements in fruits and leaves of three tree species as bioindicators in San Luis Potosi, Mexico. Ninety fruit and 90 leaf samples (30 per tree species) were collected at five sites (agricultural, suburban, commercial and services, urban, and mining), using the site and the presence of P. laevigata, S. molle, and A. farnesiana as references. Total concentrations of 13 metal elements were determined using an inductively coupled plasma mass spectrometer (ICP-MS). The species were significantly affected by Co, As, and Pb (ANOVA, p≤0.05). Considering the land use and the species, the contents determined in the leaves and fruits of the three species had sufficient and phytotoxic contents of Al, Cd, Co, Ni, Mn, Ti, and Cr, and excessive ranges with the possible phytotoxic effect of As, Cu, Pb, Zn, V, and Fe. The A. farnesiana had the highest concentrations of 12 heavy metals analyzed (HM). The variation in total metal concentrations between leaves and fruits ranged from 84.70 to 99.06%, with V, As, and Cr being prominent. The functionality of these tree species as phytoremediators and bioindicators is reviewed to evaluate environmental impacts on land use. Highlights • Tree species represent a potential bioindicator for studying environmental pollutants due to their ability to accumulate heavy metals. • The variation in total metal concentrations between leaves and fruits ranged from 84.70 to 99.06% • The contents determined in the leaves and fruits of the three species trees had sufficient and phytotoxic HM contents. • The tree species have phytoremediators capacity to evaluate environmental impacts and environmental contamination of land use.

In the past two years, the world has faced the pandemic caused by the severe acute respiratory syndrome 2 coronavirus (SARS-CoV-2), which by August of 2022 has infected around 619 million people and caused the death of 6.55 million individuals globally. Although SARS-CoV-2 mainly affects the respiratory tract level, there are several reports, indicating that other organs such as the heart, kidney, pancreas, and brain can also be damaged. A characteristic observed in blood serum samples of patients suffering COVID-19 disease in moderate and severe stages, is a significant increase in proinflammatory cytokines such as interferon-α (IFN-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interleukin-6 (IL-6) and interleukin-18 (IL-18), as well as the presence of autoantibodies against interferon-α (IFN-α), interferon-λ (IFN-λ), C-C motif chemokine ligand 26 (CCL26), CXC motif chemokine ligand 12 (CXCL12), family with sequence similarity 19 (chemokine (C-C motif)-like) member A4 (FAM19A4), and C-C motif chemokine ligand 1 (CCL1). Interestingly, it has been described that the chronic cytokinemia is related to alterations of blood-brain barrier (BBB) permeability and induction of neurotoxicity. Furthermore, the generation of autoantibodies affects processes such as neurogenesis, neuronal repair, chemotaxis and the optimal microglia function. These observations support the notion that COVID-19 patients who survived the disease present neurological sequelae and neuropsychiatric disorders. The goal of this review is to explore the relationship between inflammatory and humoral immune markers and the major neurological damage manifested in post-COVID-19 patients.

The use of functional feeds in aquaculture is currently increasing. This study aimed to assess the combined impact of dietary green microalgae Chlorella fusca and ethanol-inactivated Vibrio proteolyticus DCF12.2 (CVP diet) on thick-lipped grey mullet (Chelon labrosus) juvenile fish. The effects on intestinal microbiota and the transcription of genes related to metabolism, stress, and the immune system were investigated after 90 days of feeding. Additionally, the fish were challenged with Aeromonas hydrophila and polyinosinic–polycytidylic acid (poly I:C) to evaluate the immune response. Microbiota analysis revealed no significant differences in alpha and beta diversity between the anterior and posterior intestinal sections of fish fed the control (CT) and CVP diets. The dominant genera varied between the groups; Pseudomonas and Brevinema were most abundant in the CVP group, whereas Brevinema, Cetobacterium, and Pseudomonas were predominant in the CT group. However, microbial functionality remained unaltered. Gene expression analysis indicated notable changes in hif3α, mhcII, abcb1, mx, and tnfα genes in different fish organs on the CVP diet. In the head kidney, gene expression variations were observed following challenges with A. hydrophila or poly I:C, with higher peak values seen in fish injected with poly I:C. Moreover, c3 mRNA levels were significantly up-regulated in the CVP group 72 h post-A. hydrophila challenge. To conclude, incorporating C. fusca with V. proteolyticus in C. labrosus diet affected the microbial species composition in the intestine while preserving its functionality. In terms of gene expression, the combined diet effectively regulated the transcription of stress and immune-related genes, suggesting potential enhancement of fish resistance against stress and infections.

Quillaja saponaria is a sclerophyllus evergreen tree species distributed from 30° to 38° S in Central Chile. In this wide distribution it is expected that the species exhibits phenotypic plasticity in the mor-phology of leaves associated to climate variation; however, the information on this topic is still scarce. We studied leaf phenotypicvariation and its relationship with temperature, precipitation, and aridity in 85 stands of Q. saponaria throughout the natural distribution of the species. The results show that the basal diameter of petiole, the number of secondary veins, and the basal diameter of the principal vein increased with precipitation and decreased with aridity, while the length, basal diameter and the relative length of the petiole decreased with temperature. This confirms that phenotypic variation for foliar characters in Q. saponaria is related to climatic variables indicating an adapting capability of the species to the wide range of environmental conditions in which grows.

Objetivo: En años recientes, el reemplazo valvular aórtico vía percutánea (TAVI) ha revolucionado el tratamiento de los pacientes con estenosis aórtica, sin embargo, poca evidencia la considera como opción de tratamiento en pacientes con insuficiencia aórtica (IA), especialmente en pacientes con Insuficiencia Aórtica Pura de Válvula Nativa (IAPVN), dado que esta patología confiere múltiples retos con resultados muy variables tanto a corto como a largo plazo. Dada su alta mortalidad en caso de permanecer sin tratamiento, la primera opción de tratamiento es la cirugía de cambio valvular. Material y Métodos: Presentamos el caso de un masculino de 79 años con IAPVN grave considerado inoperable dadas las comorbilidades. De acuerdo con la decisión del equipo de Cardiología, se decidió realizar TAVI con la colocación de una Válvula Edwards SAPIEN 3. El paciente desarrolló bloqueo AV completo como única complicación y se colocó marcapasos permanente. Permaneció en clase funcional NYHA II. A los 15 meses de seguimiento presentó hemorragia intracraneal y falleció. Resultados y Conclusiones: El manejo de los pacientes con IAPVN grave sintomática con riesgo quirúrgico alto sigue siendo un reto especial. Tienen alta mortalidad si no se realiza cambio valvular a pesar de tratamiento médico. A pesar de que no se recomienda en las guías actuales, la TAVI puede ser una opción razonable para un grupo muy selecto de pacientes que son considerados inoperables.

La mitocondria cumple diversas funciones celulares, principalmente en relación con los requerimientos energéticos y la regulación de la muerte celular. Aunque todas las células de los organismos son importantes, existen algunas que resultan particularmente sobresalientes por el alcance que su desempeño pudiera tener, tal es el caso de las células beta pancreáticas, encargadas de sintetizar y liberar la insulina. En el marco de los 100 años del descubrimiento de esta hormona, con esta revisión se pretende dar a conocer los diferentes aspectos de la función celular en los que está implicada la mitocondria, así como su relevancia en términos de la salud y la enfermedad, que gira en torno a la producción de insulina y, por lo tanto, en la regulación del metabolismo de la glucosa.

BackgroundCOVID-19 requires an early diagnosis to optimize management and limit transmission. SARS-CoV-2 is able to spread effectively. Infected asymptomatic individuals have been found to be contagious. RT-qPCR is the currently recommended laboratory method for diagnosing acute infection. However, rapid antigen detection (RAD) tests are not only fast, but require less specialized training. The possibility of using RAD tests to identify asymptomatic patients is attractive, as it could effectively contribute to minimizing the hospital spread of SARS-CoV-2. The objective of the study was to determine the performance of RAD vs. RT-qPCR for the detection of asymptomatic cases in INER health personnel.MethodsIn order to follow WHO guidelines, generalized tests, a test station for health care workers was implemented on demand. A rapid test was carried out and a second sample was taken to be processed by RT-qPCR. With the results of both tests we conducted a retrospective study. Sensitivity, specificity, positive predictive value, negative predictive value and negative likelihood ratios were calculated.ResultsA total of 1640 RAD tests were performed in health care workers (mean age was 39, 69, 47% with a self-reported comorbidity). Participants provided 1,640 valid RAD/RT-qPCR test pairs with 2% testing positive via RT-qPCR. 12 RAD samples were positive for SARS-CoV-2. Overall sensitivity of the PANBIO ™ COVID-19 Ag Rapid Test test was 35.2%.ConclusionsRADs are not recommended for the detection of asymptomatic cases due to low performance.

Objective: To analyze the results of contingent screening for common aneuploidies at our center from June 2017 to June 2019. Materials and methods: Traditional screening tests were performed using a combination of biochemical markers and ultrasound measurements in the first and second trimesters to assess the risk of trisomies 21 (T21), 18 (T18) and 13 (T13). Cell-free DNA (cf-DNA) testing was offered (Harmony test) to pregnant women at high risk (>1/280 for T21 and > 1/150 for T13 and T18) and a normal early morphology scan. In positive cases, prenatal sampling was strongly recommended to confirm the results by gold standard methods (QF-PCR and karyotyping). Newborns' phenotypes were corroborated after birth in all cases. Results: In this prospective study, 8153 pregnant women were enrolled, resulting in 390 at high risk according to traditional screening tests. cfDNA testing was offered to 383 women. Traditional screening tests showed a false negative rate of 9.68% for T21. Traditional test sensitivity for T21 was 90.3%, for a false positive rate of 4.17% and a positive predictive value of 7.6%. The positive and negative predictive value for cfDNA testing was 100%. The approach used avoided invasive procedures in 91.3% of women at high risk. The prevalence of chromosomal abnormalities in the population analyzed was 1 in 164, and 1 in 210 for T21. Conclusions: Our results show that offering cf-DNA testing to women at high risk in traditional tests (including those with risks >1 in 50) significantly reduces false positives and, therefore, the number of invasive tests. Extending the use of cf-DNA testing to intermediate risk categories may be cost effective.

Abstract Background Chagas disease is considered important and presents intense inflammatory and fibrotic processes induced by the perpetuation of the parasite in the affected tissues and organs. Therefore, it is necessary to inquire about the host defense and attack mechanisms to have a more detailed knowledge about Chagas disease. MicroRNAs are found in blood, tissues and extracellular vesicles. These small regulators of gene expression are involved in physiological and pathological processes in both mammals and parasites. Several microRNAs have deregulated expression in chagasic heart disease, although little is known about their extracellular expression. Our main objective was to evaluate the involvement of miR-21, miR-146a and miR-155 in several samples from mice infected with the TcI Ninoa strain from the acute and indeterminate phases. We also explored a potential functional association of the selected microRNAs using STRING software. This software identified 23 pathways associated with Trypanosoma cruzi infection. In addition, eleven genes were identified through bioinformatics analysis, and we found that SMAD family member 5 was downregulated in both phases. This gene serves as a mediator in the TGF-β signaling pathway. Thus, forty female mice of the CD1 strain were distributed into 4 groups and the expression levels of miR-21, miR-146a and miR-155 were measured in samples of heart tissue, total plasma and plasma extracellular vesicles by quantitative real-time polymerase chain reaction. Results Overexpression of miR-21, miR-146a and miR-155 was observed in heart and plasma in both phases. Moreover, in extracellular vesicles miR-21 and miR-146a were also overexpressed in the acute phase, whereas in the indeterminate chronic phase we found only miR-146a up-regulated. Conclusions The expression of inflammatory microRNAs miR-21, miR-146a and miR-155 were up-regulated in each of the samples from acutely and chronically infected mice. The relevant finding was that miR-146a was up-regulated in each sample in both phases; therefore, this miRNA could be a possible candidate biomarker in Chagas disease.

Developments in mountain areas prone to natural hazards produce undesired impacts and damages. Thus, disaster assessment is mandatory to understand the physics of dangerous events and to make decisions to prevent hazardous situations. This work focusses on the practical implementation of methods and tools to assess a snow avalanche that affected a road at the Coll de Pal in 2018 (SE Pyrenees). This is a quite common situation in mountain roads and the assessment has to focus specially in the avalanche–road interaction, on the return periods considered and on the dynamics of the phenomena. This assessment presents the field recognition, snow and weather characterization and numerical modelling of the avalanche. Field campaigns revealed evidences of the avalanche triggering, runout trajectory and general behavior. An unstable situation of the snowpack due to a relatively large snowfall fallen some days before over a previous snowpack with weak layers, caused the avalanche triggering when an additional load was added by a strong wind-drift episode. A medium size (3) soft slab avalanche, corresponding to a return period of 15–20 years, occurred and crossed the road of the Coll de Pal pass. The event was reproduced numerically by means of the 2D-SWE based numerical tool Iber aiming to analyze the avalanche behavior. Results of the simulation corresponded with the observations (runout trajectory and snow deposit); thus, relevant information about the avalanche dynamics could be obtained. Identified differences probably come from the terrain elevation data, which represent “snow free” topography and do not consider the snowpack on the terrain.