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Risk stratification in pulmonary arterial hypertension (PAH) is essential to provide more aggressive treatment for patients at higher risk. Nevertheless, recently introduced simplified prognostic tools neglect the genetic background. Additionally, pulmonary veno-oclusive disease (PVOD) has never been considered in risk assessment strategies.We analyzed consecutive patients in the Spanish registry of PAH (REHAP) genetically tested, between 2011 and 2022. We applied the 4-strata COMPERA 2.0 model, comparing these results with an amplified score including genetics. Cox regression models were compared using Harrel c-statistics. The application of the model was specifically tested in PVOD before inclusion.We identified 298 patients tested genetically among the group of idiopathic, familial, drug-induced PAH and PVOD patients in the REHAP registry. When we analyzed only patients with all available variables of interest at baseline (World Health Organization functional class, 6-minute walk test, B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide) and included in the 4-strata model (n = 142), after a median follow-up of 58.2 months, 17.6% of patients died and 11.3% underwent lung transplant. The application of the 4-strata model in our population demonstrated a good prognostic capacity (Harrel c of 0.689), which was not improved by the introduction of genetics (c-index 0.690). This last model showed a tendency for a better identification of patients at intermediate-low and intermediate-high risk, and no differences between intermediate-high and high-risk strata.In this work, the addition of genetics to the COMPERA 4-strata model achieved a similar global prognostic capacity but changed the identification of different risk strata in a cohort of young genetically tested patients.

Recientemente la riqueza económica ha sido importante para el análisis de desarrollo económico y humano, sinembargo, algunos planteamientos teóricos fueron desarrollados por Aristóteles en un complejo pensamientoeconómico-filosófico. Este artículo es de carácter teórico y tiene como propósito exponer el significado de lariqueza en la oikonomiké y en la vida del ser humano planteado en la Política, Ética Nicomáquea y ÉticaEudemia. Este trabajo se divide en dos partes; la primera presenta brevemente el planteamiento de laeudaimonía, y la segunda expone el significado de la riqueza en ésta. Se concluye que algunos de estosplanteamientos teóricos pueden ser significativos para la denición actual del marco teórico y metodológico endesarrollo humano.

The generalized use of molecular identification tools indicated that multispecific green tides are more common than previously thought. Temporal successions between bloom-forming species on a seasonal basis were also revealed in different cold temperate estuaries, suggesting a key role of photoperiod and temperature controlling bloom development and composition. According to the Intergovernmental Panel on Climate Change, water temperatures are predicted to increase around 4°C by 2100 in Ireland, especially during late spring coinciding with early green tide development. Considering current and predicted temperatures, and photoperiods during bloom development, different eco-physiological experiments were developed. These experiments indicated that the growth of Ulva lacinulata was controlled by temperature, while U. compressa was unresponsive to the photoperiod and temperatures assayed. Considering a scenario of global warming for Irish waters, an earlier development of bloom is expected in the case of U. lacinulata. This could have significant consequences for biomass balance in Irish estuaries and the maximum accumulated biomass during peak bloom. The observed seasonal patterns and experiments also indicated that U. compressa may facilitate U. lacinulata development. When both species were co-cultivated, the culture performance showed intermediate responses to experimental treatments in comparison with monospecific cultures of both species.

En este artículo, se presenta el aprendizaje contextual como innovación en la didáctica de la Literatura para fomentar la enseñanza-aprendizaje por competencias. Resulta llamativo que la innovación pueda encontrar propuestas que cohesionan el centro educativo con su entorno próximo y que promueven la interdisciplinariedad situando a los discentes en un contexto significativo en el que se desenvuelve lo competencial. Sin duda, además de ser enfoques innovadores, son perspectivas que nos acercan a un auténtico fomento de la lectura y a una mayor proximidad a la naturaleza proteica, pluridimensional y humana que habita en los textos literarios.

Este artículo presenta el análisis urbano de los espacios públicos y áreas verdes actuales, en la ciudad de Córdoba Veracruz México, con el objetivo de identificar los indicadores presentes de un espacio saludable. Se analizaron los parques, áreas verdes, campos y canchas deportivas en relación con el número de sus habitantes y entorno urbano en donde se localizan. El espacio abierto público es indispensable para el desarrollo de las actividades físicas, medioambientales y psicológicas de los habitantes, la pertinencia de realizar una investigación en donde se analice el total de áreas verdes y espacios públicos con las que cuenta en la actualidad la ciudad permitirá determinar el estado en el que se encuentran, para su posterior intervención, considerando los parámetros establecidos por organizaciones internacionales como la OMS (Organización Mundial de la Salud) y los objetivos de la Agenda 2030 de la ONU (Organización de las Naciones Unidas)[1]. Como resultado de esta investigación se determinó el estado en el que se encuentran los espacios abiertos públicos que existen en la ciudad mediante una visita de campo y fotografías de sitio actuales. Recopilando datos e indicadores sobre: el deterioro, uso y actividades, ubicación, estado del mobiliario, estados de las instalaciones, nivel de usuarios, áreas con las que cuenta, jardines, tipo de flora, fauna, áreas recreativas y deportivas, áreas infantiles, entre otras. [1] https://www.un.org/sustainabledevelopment/es/objetivos-de-desarrollo-sostenible/

Mechanical thrombectomy (MT) has meant a change in natural history of acute ischemic stroke. Our aim is to assess the possible association between different factors and prognosis in patients treated with MT in a third degree Spanish hospital.Cross-sectional study including 198 patients underwent MT because of acute ischemic stroke between 2012 and 2020. Sociodemographic, vascular risk factors (VRF) and clinical-radiologic factors were recorded. Functional outcome was evaluated based on modified Rankin Scale (mRS) at 90 days, being mRS≤2 favorable and mRS≥3 unfavorable outcome.Mean age 67.7±13.5 years, 50.5% women. Arterial hypertension was the most prevalent VRF (65.7%). National Institute of Health Stroke Scale (NIHSS) median value at admission was 17.0 (8.0; 22.0). 40.9% of cases also received fibrinolytic treatment. Conscious sedation was performed in 66.7% patients. Median passes of MT were 2, and median duration 41min. Successful recanalization was achieved in 79.9% and mRS≤2 at 90 days was registered at 59.5% cases. Age, type 2 diabetes (T2D), number of MT passes and procedure duration were associated with mRS≥3. Successful recanalization was associated with mRS≤2. Regression model confirmed these associations in age (OR: 1.56CI%: 1.11; 2.20); T2D (OR: 3.51CI%: 1.38; 8.97) and successful recanalization (OR: 0.07CI%: 0.02; 0.28).Age, T2D and failed recanalization increase risk for unfavorable outcome at 90 days in patients with AIS treated with MT. Procedure time duration should be considered as a possible determinant factor in functional outcome.

El concepto desarrollo sustentable trajo una ideología ambiental global que llevó a crear, reformar e implementar leyes ambientales. En México, la ideología internacional de desarrollo sustentable fue tomada por gobiernos como base para crear y reformar sus leyes. Las ideologías ambientales son sistemas de creencias que regulan la actitud y el comportamiento de las relaciones humanas con la naturaleza. Existen ideologías en el derecho ambiental internacional y nacional, así como en los actores involucrados. Al aplicar la legislación, la ideología ambiental “oficial” puede ser ajena, sobre todo a actores locales. Locatarios con ideología propia, e incluso generacional, sobre la conservación y aprovechado de la naturaleza. La diferencia ideológica dificulta la aplicación de la legislación, sanciona acciones locales que van contra la ideología “oficial” y pretende moldear conductas. Al analizar documentos oficiales y revisar bases de datos, el estudio reflexiona y analiza las ideologías ambientales concurrentes en la legislación ambiental mexicana, con énfasis en la inclusión de ideologías locales. Se apreció una ideología ambiental “oficial” dominante, antropocéntrica/occidentalizada, principalmente proveniente de grupos de poder, que busca imponerse a ideologías locales.

This note presents a three-dimensional evolutionary Navier-Stokes problem solution. We use a vector field that satisfies the stationary operator to investigate the structure of the evolutionary problem. The objective of the present paper is to construct the solution to the evolutionary problem, and this solution appears as the result of a Bernoulli ordinary differential equation.

This note presents a one-dimensional nonlinear Cauchy problem solution.

Since January 23, 2019, several countries, including the United States and the United Kingdom, have recognized the speaker of the Venezuela National Assembly, deputy Juan Guaidó, as interim president until free and fair presidential elections are called. That recognition was a consequence of the repudiation of the 2018 presidential election, in which the incumbent president, Nicolás Maduro, was fraudulently proclaimed president for the term that began on January 10, 2019. A few days later, on February 6, 2019, the Venezuelan National Assembly approved a special law, the Statute that Governs the Transition to Democracy to Restore the Enforcement of the Constitution of the Bolivarian Republic of Venezuela (the Transition Statute). The primary purpose of the Transition Statute was to regulate the exercise of the presidency by the speaker of the National Assembly acting as interim president, based on Article 233 of the Venezuelan Constitution.

This paper presents a robust multi-objective optimal design (RMOP) of a passenger car with a semi-active suspension system. The mean-effective values of the root mean square of the passenger’s head acceleration, suspension travel, and tire deflection are considered as design objectives. The passive components of the suspension and the design details of the Linear Quadratic Regulator (LQR) algorithm are used as design parameters. During the design, global sensitivity analysis is carried out using the Fourier Amplitude Sensitivity Test (FAST) to specify the elements of the model that can highly alter the design objectives. The mass of the passenger’s head and upper body, the mass of the passenger’s lower body and cushion, passenger and cushion’s elastic properties, and the sprung mass of the vehicle are selected for the sensitivity analysis. Results show that the design criteria are very sensitive to the variations in the sprung mass of the vehicle as compared to the other parameters. As a result, the variations in this parameter and passive elements of the suspension system are considered. Constraints are applied on the objectives in compliance with the requirements of ISO 2631-1 on the design of car suspension systems. The optimization problem is solved by the NSGA-II (non-dominated sorting genetic algorithm II) and robust Pareto front and set are obtained. The Pareto set includes multiple design options from which the decision-maker can choose to implement. Responses of the passenger’s head acceleration, suspension travel, and tire deflection show that the robust multi-objective design algorithm (RMOA) is very effective and guarantees less sensitivity to the suspension passive elements.

Objective: The objective of this study was to describe the rates of adverse clinical outcomes, including all-cause mortality, heart failure (HF) hospitalization, myocardial infarction, and stroke, in patients newly diagnosed with HF to provide a comprehensive picture of HF burden. Methods: This was a retrospective and observational study, using the BIG-PAC database in Spain. Adults, newly diagnosed with HF between January 2013 and September 2019 with ≥1 HF-free year of enrolment prior to HF diagnosis, were included. Results: A total of 19,961 patients were newly diagnosed with HF (43.5% with reduced ejection fraction (EF), 26.3% with preserved EF, 5.1% with mildly reduced EF, and 25.1% with unknown EF). The mean age was 69.7 ± 19.0 years; 53.8% were men; and 41.0% and 41.5% of patients were in the New York Heart Association functional classes II and III, respectively. The baseline HF treatments included beta-blockers (70.1%), renin–angiotensin system inhibitors (56.3%), mineralocorticoid receptor antagonists (11.8%), and SGLT2 inhibitors (8.9%). The post-index incidence rates of all-cause mortality, HF hospitalization, and both combined were 102.2 (95% CI 99.9–104.5), 123.1 (95% CI 120.5–125.7), and 182 (95% CI 178.9–185.1) per 1000 person-years, respectively. The rates of myocardial infarction and stroke were lower (26.2 [95% CI 25.1–27.4] and 19.8 [95% CI 18.8–20.8] per 1000 person-years, respectively). Conclusions: In Spain, patients newly diagnosed with HF have a high risk of clinical outcomes. Specifically, the rates of all-cause mortality and HF hospitalization are high and substantially greater than the rates of myocardial infarction and stroke. Given the burden of adverse outcomes, these should be considered targets in the comprehensive management of HF. There is much room for improving the proportion of patients receiving disease-modifying therapies.

Proprioception plays a crucial role in laryngeal function. Further, dysfunctional proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia and vocal fold paresis. Despite this, the physiology of laryngeal proprioception is not well-understood. Controversy remains over whether canonical proprioceptive organs, like muscle spindles (MS) even exist in the intrinsic laryngeal muscles (ILM). Vesicular Glutamate Transporter 1 (VGLUT1) expression has been described in the sensory afferents of MS. This study’s primary aim is to determine whether the ILM contain MS using VGLUT1. This is a novel approach, as prior studies have relied on morphology and myosin composition to study this question. Secondarily, we describe the pattern of VGLUT1 expression in the rat larynx, Larynges of 62 Sprague-Dawley rats distributed across 5 age groups (P3, P8, P11, P14-15, and adult), were sectioned and immunostained for VGLUT1 and beta-tubulin III. Other markers (S46, GNAT3, PLCβ2, S100b, CGRP) were used to further characterize identified afferent innervation. Of 62 rats, MS were identified in the lateral thyroarytenoid muscles of just three P8 rats, and no golgi tendon organs (GTO) were seen. VGLUT1-positive intramuscular receptor-like entities were observed ILM, and VGLUT1-positive nerve endings were observed in the laryngeal mucosa, concentrated around the arytenoid cartilage. Employing VGLUT1 immunostaining, this study shows that rat intrinsic laryngeal muscles rarely express MS and do not express GTO. This leaves open the possibility that the larynx exhibits a unique proprioceptive apparatus. VGLUT1-positive intramuscular and mucosal structures provide candidates for an alternative system. Further defining the role of these sensory organs will increase our understanding of vocal fold function and ultimately lead to better treatment of vocal fold disorders.KEY POINTSDysfunctional laryngeal proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia, and vocal fold paresis. Unlike proprioception of skeletal muscles, proprioception of the intrinsic laryngeal muscles is poorly understood.In the present study we demonstrate that canonical proprioceptive organs (muscles spindles and Golgi tendon organs) are rarely expressed in the rat larynx, by studying the expression pattern of VGLUT1.We also demonstrate the presence of other sensory innervation and structures which may contribute to an alternative proprioceptive circuitry, which requires further study.

The larynx is an organ of the upper airway that participates in breathing, glutition, voice production, and airway protection. These complex functions depend on vocal fold (VF) movement, facilitated in turn by the action of the intrinsic laryngeal muscles (ILM). The necessary precise and near-instantaneous modulation of each ILM contraction relies on proprioceptive innervation of the larynx. Dysfunctional laryngeal proprioception likely contributes to disorders such as laryngeal dystonia, dysphagia, vocal fold paresis, and paralysis. While the proprioceptive system in skeletal muscle derived from somites is well described, the proprioceptive circuitry that governs head and neck structures such as VF has not been so well characterized. For over two centuries, researchers have investigated the question of whether canonical proprioceptive organs, muscle spindles, and Golgi tendon organs, exist in the ILM, with variable findings. The present work is a state-of-the-art review of the peripheral component of laryngeal proprioception, including current knowledge of canonical and possible alternative proprioceptive circuitry elements in the larynx.

IntroductionBefore the pandemic, suicide was already considered a global public health problem. The outbreak of COVID-19, a coronavirus-related infectious disease, began to impact people's physical and mental health. The factors that either contribute to or mitigate this risk need to be better understood, and this can only be accomplished through research. Therefore, this study aimed to study the prevalence of suicidal ideation and behavior in Tamaulipas, Mexico, during the COVID-19 pandemic.MethodsA quantitative, descriptive, and cross-sectional study was conducted. The sample consisted of 659 participants, of whom 194 (29.5%) were men and 465 (70.5%) participants were oldwomen, ranging in age between 16 and 68 years (M = 22.56, SD = 7.26). An adapted version of the Spanish version of the Columbia Suicidal Severity Rating Scale was used to assess the seriousness of suicidal ideation and behavior.ResultsThe higher rates of suicidal indicators were suicidal ideation with “wish to dead” (39.9%), while the lower was suicidal ideation with a specific plan (8.2%). A total of 18.2% of participants reported “suicidal attempts before COVID-19,” of whom 40% reported “suicidal attempts in the last 3 months.” Suicidal behavior rates were lower: 13.7% of participants reported “non-specific preparatory behavior” and 13.3% reported “actual suicide attempts.” Women were more likely than men to exhibit almost all indicators of suicidal ideation and behavior (OR = 1.63–2.54; 95% CI = 1.11–2.41, 1.76–3.68), as well as confinement (OR = 2.60; 95% CI = 1.73–3.91). Confinement for more than 40 days (OR = 0.55–0.66; 95% CI = 0.40–0.75, 0.47–0.93) and knowing a person infected with COVID-19 (OR = 1.57–2.01; 95% CI = 1.02–2.42, 1.20–3.34) were associated with a higher risk of exhibiting several suicidal indicators and having previously attempted suicide.ConclusionBeing a woman, knowing a person infected with COVID-19, and being confined, especially for longer than 40 days, are all risk factors for suicidal ideation. Therefore, intervention programs are needed to reduce the suicide risk prevalence, especially these days because of the influence of the pandemic, and should be primarily focused on those who present the risk factors associated with suicidal behavior identified in this study.

Natural evolution has provided multicellular organisms with sophisticated functionalities and repair mechanisms for surviving and preserve their functions after an injury and/or infection. In this context, biological systems have inspired material scientists over decades to design and fabricate both self-healing polymeric materials and soft actuators with remarkable performance. The latter are capable of modifying their shape in response to environmental changes, such as temperature, pH, light, electrical/magnetic field, chemical additives, etc. In this review, we focus on the fusion of both types of materials, affording new systems with the potential to revolutionize almost every aspect of our modern life, from healthcare to environmental remediation and energy. The integration of stimuli-triggered self-healing properties into polymeric soft actuators endow environmental friendliness, cost-saving, enhanced safety, and lifespan of functional materials. We discuss the details of the most remarkable examples of self-healing soft actuators that display a macroscopic movement under specific stimuli. The discussion includes key experimental data, potential limitations, and mechanistic insights. Finally, we include a general table providing at first glance information about the nature of the external stimuli, conditions for self-healing and actuation, key information about the driving forces behind both phenomena, and the most important features of the achieved movement.

Cytokines, demyelination and neuroaxonal degeneration in the central nervous system are pivotal elements implicated in the pathogenesis of multiple sclerosis (MS) and its nonclinical model of experimental autoimmune encephalomyelitis (EAE). Phycocyanobilin (PCB), a chromophore of the biliprotein C-Phycocyanin (C-PC) from Spirulina platensis, has antioxidant, immunoregulatory and anti-inflammatory effects in this disease, and it could complement the effect of other Disease Modifying Treatments (DMT), such as Interferon-β (IFN-β). Here, our main goal was to evaluate the potential PCB benefits and its mechanisms of action to counteract the chronic EAE in mice. MOG35-55-induced EAE was implemented in C57BL/6 female mice. Clinical signs, pro-inflammatory cytokines levels by ELISA, qPCR in the brain and immunohistochemistry using precursor/mature oligodendrocytes cells antibodies in the spinal cord, were assessed. PCB enhanced the neurological condition, and waned the brain concentrations of IL-17A and IL-6, pro-inflammatory cytokines, in a dose-dependent manner. A down- or up-regulating activity of PCB at 1 mg/kg was identified in the brain on three (LINGO1, NOTCH1, and TNF-α), and five genes (MAL, CXCL12, MOG, OLIG1, and NKX2-2), respectively. Interestingly, a reduction of demyelination, active microglia/macrophages density, and axonal damage was detected along with an increase in oligodendrocyte precursor cells and mature oligodendrocytes, when assessed the spinal cords of EAE mice that took up PCB. The studies in vitro in rodent encephalitogenic T cells and in vivo in the EAE mouse model with the PCB/IFN-β combination, showed an enhanced positive effect of this combined therapy. Overall, these results demonstrate the anti-inflammatory activity and the protective properties of PCB on the myelin and support its use with IFN-β as an improved DMT combination for MS.

Our objective was to analyze the sources, characteristics, tone, and content of the most viewed YouTube videos in Spanish about Covid-19 vaccines. In February 2021, a search was carried out on YouTube using the terms “Vacuna Covid,” “Vacuna coronavirus,” and “Vacuna Covid19.” Associations between tone, source, and others variables (e.g. number of views or dislikes) were studied with a Mann–Whitney U-test and a chi-square test. A total of 118 videos were analyzed; 63.6% were originated from Mexico and the USA; media created 57.6% of the videos. Positive tone was observed in 53.4%. The most discussed topics were target groups for vaccination (38.9%) and safety (43.2%). The 68 videos produced by media accumulated 31,565,295 views (55.0% of views), and the 19 videos created by health professionals obtained 10,742,825 views (18.7% of views). A significantly smaller number of likes was obtained in videos of media compared to those created by health professionals (p = .004). Videos made by health professionals, compared to those of media, showed a greater positive tone (OR = 3.09). Hoaxes/conspiracy theories were identified in 1.7% of the videos. Monitoring that the information on YouTube about Covid-19 vaccines is reliable should be a central part of Covid-19 vaccination campaigns.

Introduction This study aimed to describe utilization patterns, persistence, resource utilization and costs in patients with type 2 diabetes mellitus initiating treatment with glucagon-like peptide 1 receptor agonists in routine clinical practice in Spain. Methods This retrospective study of medical records in the Big-Pac database identified adults starting treatment with once-weekly (QW) dulaglutide, exenatide-QW or once-daily liraglutide between 1 November 2015 and 30 June 2017. Patients were followed for up to 18 months from treatment initiation. Data on clinical characteristics of patients, treatment patterns, average daily dose and costs were obtained for the three cohorts. Persistence over the 18-month period was evaluated using Kaplan–Meier curves. All analyses were descriptive. Results A total of 1402 patients were included in this study (dulaglutide [n = 492], exenatide-QW [n = 438] or liraglutide [n = 472]); 52.8% were men, and the mean (SD) age was 62 (11) years, glycated haemoglobin (HbA1c) was 8.1% (1.2) and body mass index was 35.5 (3.2) kg/m2 at treatment initiation. Persistence at 18 months was 59.1% (95% confidence interval [CI] 54.8–63.4) for dulaglutide, 45.7% (95% CI 41.0–50.4) for exenatide-QW and 46.6% (95% CI 42.1–51.1) for liraglutide. The average (SD) dose was 1.2 (0.4) mg/week for dulaglutide, 1.9 (0.3) mg/week for exenatide-QW and 1.1 (0.3) mg/day for liraglutide. The average reduction in HbA1c levels at 1 year was − 0.68% for patients who initiated dulaglutide, − 0.54% for patients who initiated exenatide-QW and − 0.50% for patients who initiated liraglutide. The mean (SD) total annual health care costs were €4072 (1946) for dulaglutide, €4418 (2382) for exenatide-QW and €4382 (2389) for liraglutide. Conclusion Results suggest that patients who started treatment with dulaglutide had higher persistence over 18 months, presented lower HbA1c levels at 12 months and incurred lower annual total healthcare costs than patients who initiated exenatide-QW or liraglutide. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01039-5., Plain Language Summary Type 2 diabetes has a major impact on patients psychologically and socially, as well as on healthcare costs. The glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are drugs that help maintain blood sugar at healthy levels. They are often used as the first injectable drugs if oral treatments are no longer effective. This study aimed to analyse the use of GLP-1 RAs, and the costs involved, among patients with type 2 diabetes who started treatment with once-weekly dulaglutide, once-weekly exenatide or liraglutide in routine clinical practice in Spain. An electronic database of medical records was used to obtain data from 1402 patients who started treatment with these drugs and were followed for a 1.5-year period. Results of this study suggest that patients who were prescribed dulaglutide stayed on their treatment longer and could reduce their blood sugar levels more efficiently, and at a lower cost, than those who received once-weekly exenatide or liraglutide. These findings could be helpful to physicians prescribing these drugs when considering how to improve the management of type 2 diabetes. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01039-5.

The current pandemic is caused by the coronavirus disease 2019 (COVID-19), which is, in turn, induced by a novel coronavirus (SARS-CoV-2) that triggers an acute respiratory disease. In recent years, the emergence of SARS-CoV-2 is the third highly pathogenic event and large-scale epidemic affecting the human population. It follows the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. This novel SARS-CoV-2 employs the angiotensin-converting enzyme 2 (ACE2) receptor, like SARS-CoV, and spreads principally in the respiratory tract. The viral spike (S) protein of coronaviruses facilities the attachment to the cellular receptor, entrance, and membrane fusion. The S protein is a glycoprotein and is critical to elicit an immune response. Glycosylation is a biologically significant post-translational modification in virus surface proteins. These glycans play important roles in the viral life cycle, structure, immune evasion, and cell infection. However, it is necessary to search for new information about viral behavior and immunological host's response after SARS-CoV-2 infection. The present review discusses the implications of the CoV-2 S protein glycosylation in the SARS-CoV-2/ACE2 interaction and the immunological response. Elucidation of the glycan repertoire on the spike protein can propel research for the development of an appropriate vaccine.

(1) Background: Early response after acute myocardial infarction (AMI) prevents extensive cardiac necrosis, in which inflammation resolution, including expression of anti-inflammatory interleukin-10 (IL-10), may play a key role. (2) Methods: We synthesized NIL10, a micelle-based nanoparticle, to target IL-10 receptor in mice and pigs subjected to AMI. (3) Results: Administration of NIL10 induced cardiac protection of wild-type and IL-10 knockout mice and pigs subjected to AMI. Cardiac protection was not induced in IL-10-receptor null mice, as shown by a significant recovery of cardiac function, in which inflammatory foci and fibrosis were strongly reduced, together with the finding that resolving M2-like macrophage populations were increased after day 3 of reperfusion. In addition, anti-inflammatory cytokines, including IL-4, IL-7, IL-10, IL-13, IL-16, and IL-27 were also elevated. Mechanistically, NIL10 induced activation of the IL-10 receptor/STAT-3 signaling pathway, and STAT3-dependent inhibition of nuclear translocation of pro-inflammatory NF-ĸB transcription factor. (4) Conclusions: Taken together, we propose using NIL10 as a novel therapeutic tool against AMI-induced cardiac damage. This research was funded by CZ: “Universidad Francisco de Vitoria (grant numbers 2017/18)”, “Proyectos de i+D+I, from the program Investigación orientada a los retos de la sociedad, cofounded by Fondo Europeo de Desarrollo Regional (FEDER) A way to achieve Europe (MINECO/AEI/FEDER/EU SAF2017-87342-R), (MICINN/AEI/FEDER/EU PID2020-118371RBI00)”, and “Proyectos de i+D+I, from the program Investigación orientada a los retos de la sociedad, cofounded by Fondo Europeo de Desarrollo Regional (FEDER) A way to achieve Europe PRUEBA DE CONCEPTO (MICINN/AEI/FEDER/EU PDC2021-121817-100); MS: “Ayudas para realización de proyectos de investigación Junta de Comunidades de Castilla La Mancha SBPLY/19/180501/000055, cofounded by Fondo Europeo de Desarrollo Regional (FEDER). A way to achieve Europe.”; MF: “Comunidad Autonoma de Madrid and Universidad Complutense de Madrid for research project No. 2017-T1/BIO-4992 Accion de Atracción de Talento”. Sí

In the context of the COVID-19 pandemic, the co-circulation of influenza and SARS-CoV-2 viruses may have severe complications for vulnerable populations. For this reason, the World Health Organization pointed to the 2020–2021 anti-influenza campaign as being of special relevance. Our aim was to assess the 2020–2021 influenza vaccination coverage, and its associated factors, among patients in a Spanish multiple sclerosis (MS) unit. A cross–sectional study was conducted. People attending the MS unit of the Clinical Hospital of Zaragoza during 2020 were included. Variables were obtained by reviewing records. Associations with 2020–2021 influenza vaccination were analyzed using bivariate analysis and a multiple logistic regression model. A total of 302 patients were studied; 62.6% were women, whose mean age (standard deviation) was 47.3 (11.5) years. The 2020–2021 influenza vaccination coverage was 55.3% (59.8% in women and 47.8% in men). A total of 89.7% had at least one other indication for vaccination (e.g., immunosuppressive treatment in 225 patients). The variables associated with getting vaccinated were being female (adjusted odds ratio (95% confidence interval) (aOR (95%CI) = 2.12 (1.12–3.99)), having received the 2019–2020 influenza vaccine (aOR (95%CI) = 31.82 (14.71–68.86)) and being born in Spain (aOR (95%CI) = 12.91 (1.07–156.28)). Coverage is moderate compared to other countries. It is necessary to develop strategies to improve it, especially in men and those born outside Spain.

Gracilarioids and Gigartinales are of great economic importance due to the phycocolloids they contain in their cell wall and are used in different industries worldwide. Field and laboratory cultures of two species of red seaweeds (Gracilaria gracilis and Chondracanthus teedei), confirmed after DNA analysis, were carried out to foster the increasing use of this species in Spain as a food source. Vegetative cultures carried out in an open-lock gate within a traditional salina in the ay of Cadiz (Southern Spain) rendered maximum growth rates in April (3.64% day−1) for G. gracilis and in November (4.68% day−1) for C. teedei, the latter showing significant differences between the months of the year. For laboratory cultures, samples of the two species used for sporulation were obtained from tidal creeks in several nearby locations of the Bay. In order to grow fertile carposporophytes from spores, Provasoli enriched seawater medium (ES medium), Miquel A + B and f/2 were used as culture medium at a temperature of 18 °C and irradiance of 30 µmol m−2 s−1 in 12:12 h photoperiod. Both species developed a basal disc after 12–15 days in ES medium and Miquel A + B, and new microscopic seedlings were observed at 20–25 days in ES medium. With f/2 medium, no growth was observed after sporulation. The life cycle of G. gracilis was completed in ES medium over a period of 11 months with a mean growth rate of 3.28% day−1. The present study is an important step towards the development of seaweed cultivation in the Bay of Cadiz, especially in integrated multi-trophic cultivation in salinas as part of the more sustainable use of the marine resources in coastal communities.

Low socioeconomic status (SES) and living in a rural environment are associated with poorer health and a higher number of amputations among the population at large. The purpose of this study is to determine the influence of low SES and of the degree of urbanization on the short-term and long-term results of patients after revascularization for peripheral artery disease.An observational retrospective follow-up study of 770 patients operated on for peripheral artery disease at three university centers in north-western Spain from January 2015 to December 2016. The events studied were Rutherford classification of severity upon admission, direct amputation, amputations in the follow-up period, new revascularization procedures, major adverse cardiovascular events (MACE), and overall mortality. Mean personal income and income of the household associated with the street in which each patient lived and the degree of urbanization in three areas as per Eurostat criteria: densely populated areas, intermediate density areas, and thinly populated areas. Comorbidity, surgical, and follow-up variables were also collected. Descriptive analysis and Cox regression were used. Approval was obtained from the regional ethics committee.Median follow-up was 47.5 months. MACE occurred in 21.5% of the series and overall mortality was 47.0%. Living in a thinly populated area is associated with a lower risk of MACE (adjusted subhazard ratio = 0.60; 95% confidence interval [CI]: 0.39-0.91). Overall survival is lower in intermediate density area patients (adjusted Hazard Ratio = 1.46; 95% CI: 1.07-2.00). The third quartile of mean personal and household income is associated with a higher risk of major amputation at follow-up (adjusted Odds Ratio 1.92, 95% CI: 1.05-3.52 and adjusted Odds Ratio 1.93, 95% CI: 1.0.3-3.61, respectively).Patients who live in a densely populated area run a higher risk of MACE. SES is neither associated with worse outcomes after surgery nor with MACE in long-term follow-up.

La COVID-19 está demostrando la necesidad del Estado Administrativo, para asegurar la satisfacción de necesidades diversas y complejas, desde contener la enfermedad en medio de la regulación de emergencia, hasta brindar alivio económico a sectores vulnerables. Al mismo tiempo, la pandemia está mostrando la fragilidad del Estado Administrativo, debido a la brecha de capacidad estatal que deriva en áreas de limitada estatalidad, esto es, tareas que las Administraciones Públicas no pueden atender. En consecuencia, la post-pandemia requerirá del Derecho Administrativo orientado a reforzar la capacidad estatal y asegurar la protección del bien común, con base en los estándares de la buena administración. Desde el Derecho Administrativo fallido, es necesario evolucionar hacia un Derecho Administrativo efectivo.

Mientras en los países culturalmente anglosajones cada vez es menor la tendencia a tener policías de corte y estilo militar, en los de cultura latina es todo lo contrario. Incluso, en alguns existe una forma de entender la seguridad con un enfoque paralelo de estamentos operando simultáneamente, uno de naturaleza militar y otro de naturaleza civil. Dentro de este texto nos concentraremos en poner bajo relieve las similitudes y diferencias que se puedan apreciar respecto de la Guardia Civil Española, institución policíal de carácter hispano, y la institución mexicana de reciente creación, la Guardia Nacional. La relación histórica entre España y México permite realizar un breve esbozo comparativo para presentar a continuación una base para comprender la evolución de sus fuerzas policiales y cómo es que la seguridad pública ha sido concebida y puesta en marcha en ambos países.

Aims: To evaluate the cost-effectiveness of five control treatments (pesticides) for an Alternaria fungi variety in a citrus grove in Mexico. Study Design: Field applications of pesticides were used to combat an infestation of the Alternaria fungus. Place and Duration of the Study: The study took place in an orange citrus grove in Ciudad Fernandez, San Luis Potosí, Mexico, from October 2018 to August 2019. Methodology: Field trials with five control treatments were applied to randomly selected rows of infected orange trees. The assessment of treatments was carried out using the multi-criteria decision method (MCDM) known as ELECTRE with six evaluation criteria: cost, effectiveness, toxicity (e.g., environmental impact), difficulty of preparation, ease of application, and expiration date. Results: The results reveal that the best option to control the fungus of the Alternaria is the use of a biological product based on microorganisms, instead of standard options such as agrochemicals, or synthetic preparations known as “broths.” A sensitivity analysis reveals that the result may be affected by changing the weight of the criteria. Conclusion: The best treatment is the biological product because it is the most effective treatment to control the fungi plague, it is not toxic or expensive, and it does not have a measurable impact on the environment. However, the results are sensitive to changes in the weight of the criteria.

There are several methods for modeling surface roughness in computerized numerical control (CNC) milling process. This work proposes for the first time the use of response surface methodology (RSM) and a variant of the multiquadric radial basis function (MRBF) for the modeling of surface roughness (Ra) of graphite generated by means of the CNC milling process. In this variant, a norm with coefficients (weights) denoting the weighting of the effects of machining parameters is used. The machining parameters that have been most reported in literature were considered, which are cutting speed (S), feed rate (F), and cutting depth (D). Three mathematical models were developed to adjust the values of surface roughness: one model was obtained using RSM and two others were generated with the variant of MRBF. Values were assigned to effects of the weighted norm reducing it to the Euclidean norm, named Euclidean norm model (ENM). For the weighted norm model (WNM), values of effects of the machining parameters calculated by means of a factorial design were considered. Finally, in each model, the mean absolute percentage error (MAPE) was calculated: the lowest value and highest value of MAPE were obtained with response surface methodology model (RSMM) and ENM, respectively. However, lowest surface roughness was estimated and generated experimentally in graphite specimens with the machining parameter values obtained by means of WNM.

In real-world problems, uncertainties (e.g., errors in the measurement, precision errors) often lead to poor performance of numerical algorithms when not explicitly taken into account. This is also the case for control problems, where optimal solutions can degrade in quality or even become infeasible. Thus, there is the need to design methods that can handle uncertainty. In this work, we consider nonlinear multi-objective optimal control problems with uncertainty on the initial conditions, and in particular their incorporation into a feedback loop via model predictive control (MPC). In multi-objective optimal control, an optimal compromise between multiple conflicting criteria has to be found. For such problems, not much has been reported in terms of uncertainties. To address this problem class, we design an offline/online framework to compute an approximation of efficient control strategies. This approach is closely related to explicit MPC for nonlinear systems, where the potentially expensive optimization problem is solved in an offline phase in order to enable fast solutions in the online phase. In order to reduce the numerical cost of the offline phase, we exploit symmetries in the control problems. Furthermore, in order to ensure optimality of the solutions, we include an additional online optimization step, which is considerably cheaper than the original multi-objective optimization problem. We test our framework on a car maneuvering problem where safety and speed are the objectives. The multi-objective framework allows for online adaptations of the desired objective. Alternatively, an automatic scalarizing procedure yields very efficient feedback controls. Our results show that the method is capable of designing driving strategies that deal better with uncertainties in the initial conditions, which translates into potentially safer and faster driving strategies., Comment: 28 pages, 14 figures, 7 tables

In this paper, a new method for automatic filter coefficient calculation in lifting scheme wavelet transform for image lossless compression is proposed. Actually, there is no specific rule for setting filter coefficients (a, b). Therefore, this work proposes an automatic method to calculate the filter coefficients depending on the spectral analysis of each image. Also, filter coefficients are determined for five decomposition levels and for each quadrant through applying the discrete wavelet transform in the lossless image compression problem. Spectral patterns are computed and fixed into small length vectors for building different wavelet decomposition levels; these vectors are automatically computed using a 1-NN classifier. Experimental results over standard images show that calculating the wavelet filter coefficients using the proposed method generates higher compression rates (in entropy and bitstream values) against standard wavelet and linear prediction filters.

Multi-objective evolutionary algorithms (MOEAs) have been successfully applied for the numerical treatment of multi-objective optimization problems (MOP) during the last three decades. One important task within MOEAs is the archiving (or selection) of the computed candidate solutions, since one can expect that an MOP has infinitely many solutions. We present and analyze in this work ArchiveUpdateHD, which is a bounded archiver that aims for Hausdorff approximations of the Pareto front. We show that the sequence of archives generated by ArchiveUpdateHD yields under certain (mild) assumptions with a probability of one after finitely many steps a Δ+-approximation of the Pareto front, where the value Δ+ is computed by the archiver within the run of the algorithm without any prior knowledge of the Pareto front. The knowledge of this value is of great importance for the decision maker, since it is a measure for the “completeness” of the Pareto front approximation. Numerical results on several well-known academic test problems as well as the usage of ArchiveUpdateHD as an external archiver within three state-of-the-art MOEAs indicate the benefit of the novel strategy.

Introducción: La enfermedad renal crónica es un problema de salud pública que requiere de la participación activa de los individuos que la padecen para lograr una buena adherencia a los tratamientos. Objetivo: Realizar un diagnóstico participativo para identificar problemáticas de pacientes con enfermedad renal crónica y su familias. Desarrollo: se realiza un diagnóstico participativo de las percepciones de salud de personas con enfermedad renal crónica, su familia y otros actores, en relación a las experiencias de su atención, lo que permitió identificar debilidades en las intervenciones de los equipos de salud, educación en salud y salud mental, siendo las problemáticas prioritarias para los usuarios/as las relacionadas con educación en salud e intervenciones de los equipos, desde las cuales se plantearon propuestas de solución. Conclusión: El diagnóstico participativo permitió evidenciar la importancia de explorar las percepciones de las personas con enfermedad renal crónica durante su proceso de atención, con el fin de garantizar cuidados desde una perspectiva integral.

Carbon–carbon (C–C) bond formation is the key reaction in organic synthesis to construct the carbon framework of organic molecules. The continuous shift of science and technology toward eco-friendly and sustainable resources and processes has stimulated the development of catalytic processes for C–C bond formation based on the use of renewable resources. In this context, and among other biopolymer-based materials, lignin has attracted scientific attention in the field of catalysis during the last decade, either through its acid form or as a support for metal ions and metal nanoparticles that drive the catalytic activity. Its heterogeneous nature, as well as its facile preparation and low cost, provide competitive advantages over other homogeneous catalysts. In this review, we have summarized a variety of C–C formation reactions, such as condensations, Michael additions of indoles, and Pd-mediated cross-coupling reactions that were successfully carried out in the presence of lignin-based catalysts. These examples also involve the successful recovery and reuse of the catalyst after the reaction.

Rationale: Early response after acute myocardial infarction (AMI) is crucial to prevent extensive cardiac necrosis. Interleukin-10 (IL-10) is a key antiinflammatory cytokine, whose expression is closely associated with macrophage polarization towards inflammation resolution. Results: We synthesized NIL10, a micelle-based nanoparticle conjugated to IT9302, a peptide homologue to IL-10 functional domain, with the aim of targeting IL-10 receptor in mice and pigs subjected to AMI. Intravenous administration of 1 mg/kg NIL10 improved the cardiac function of mice and pigs subjected to AMI, as shown by a significant recovery of the left ventricle ejection fraction (LVEF) by days 3 and 7 after AMI, when compared to the levels found in animals injected with NIL10SC, a nanoparticle conjugated with the peptide in a scrambled orientation, in which inflammatory foci and fibrosis were strongly elevated. In IL-10 null mice subjected to AMI, NIL10 also improved heart contractility, while in IL10 receptor deficient animals, NIL10 had no effect. To test whether NIL10 may induce macrophage polarization, M2 macrophage populations were increased after day 3 of reperfusion, in which anti-inflammatory cytokines, including IL4, IL7, IL10, IL13, IL16 and IL27 were also elevated in mice and pigs injected with NIL10. Mechanistically, NIL10 induced activation of the IL-10 receptor/STAT-3 signaling pathway, and STAT3-dependent inhibition of pro-inflammatory NF-kB transcription factor nuclear translocation, as evidenced by inhibition of nuclear p65 in macrophages stimulated with 500 mM LPS in response to incubation with NIL10, and prevented by co-incubation with the STAT-3 pharmacological inhibitor STATTIC, as also evidenced by testing the NF-kB -dependent readout iNOS gene expression with same results. Conclusions: Our findings propose NIL10 nanoparticles as a novel compound to improve cardiac function after myocardial infarction, to preventing cardiac necrosis by inducing polarization toward M2-resolving macrophages, through inhibition of STAT3-induced nuclear translocation of NF-kB.

Background: Ischemic stroke produces a large health impact worldwide, with scarce therapeutic options. Objective: This study aimed to reveal the role of NADPH oxidase and neuroinflammatory genes in the cerebral anti-ischemic effects of C-Phycocyanin (C-PC), the chief biliprotein of Spirulina platensis. Methods: Rats with either focal cerebral ischemia/reperfusion (I/R) or acute brain hypoperfusion, received C-PC at different doses, or a vehicle, for up to 6 h post-stroke. Neurological, behavioral and histochemical parameters were assessed in I/R rats at 24 h. Cerebral gene expression and hippocampal neuron viability were evaluated in hypoperfused rats at acute (24 h) or chronic phases (30 days), respectively. A molecular docking analysis of NOX2 and C-PC-derived Phycocyanobilin (PCB) was also performed. Results: C-PC, obtained with a purity of 4.342, significantly reduced the infarct volume and neurological deficit in a dose-dependent manner, and improved the exploratory activity of I/R rats. This biliprotein inhibited NOX2 expression, a crucial NADPH oxidase isoform in the brain, and the superoxide increase produced by the ischemic event. Moreover, C-PC-derived PCB showed a high binding affinity in silico with NOX2. C-PC downregulated the expression of pro-inflammatory genes (IFN-γ, IL-6, IL-17A, CD74, CCL12) and upregulated immune suppressive genes (Foxp3, IL-4, TGF-β) in hypoperfused brain areas. This compound also decreased chronic neuronal death in the hippocampus of hypoperfused rats. Conclusion: These results suggest that the inhibition of cerebral NADPH oxidase and the improvement of neuroinflammation are key mechanisms mediating the neuroprotective actions of C-PC against brain ischemia.

Introducción y objetivos La quinasa ligada a integrina (ILK) endotelial controla la producción del óxido nítrico, modulando señales de transducción al interior celular. La disminución de ILK endotelial se ha relacionado con la calcificación valvular. Analizamos la asociación de la ILK con la calcificación de la válvula aórtica. Métodos Estudio observacional, unicéntrico y prospectivo. Recogimos tejido valvular aórtico de pacientes intervenidos de estenosis aórtica, y controles de válvulas no calcificadas. Cuantificamos los niveles de ILK endotelial empleando técnicas de análisis molecular, así como marcadores de crecimiento óseo (BMP2 y RUNX2). Para el control de factores de confusión empleamos regresión logística múltiple por pasos, introduciendo parámetros relacionados con la aterosclerosis y calcificación valvular (edad, DM, HTA, insuficiencia renal). Resultados Obtuvimos muestras de 75 pacientes y 28 controles. El 69,9% eran varones, la edad media fue de 67 años (DE 9,59 años). Los niveles de ILK fueron significativamente más bajos en válvulas patológicas que en controles (0,96 vs. 0,76; p < 0,001). Existió correlación lineal negativa significativa entre la ILK y la calcificación valvular (coeficiente de Pearson = −0,35; p = 0,002). En el modelo multivariante, ILK presentó una asociación significativa con la calcificación valvular (OR 0,068; p < 0,001), así como la DM (OR 11,80; p = 0,03). Observamos un aumento de marcadores de crecimiento óseo según avanzaba la calcificación, con correlación inversa significativa de ILK y BMP2 (R = −0,417; p < 0,001) y RUNX2 (R = −0,587; p < 0,001). Conclusiones La disminución de la expresión endotelial de ILK puede influir en la calcificación de la válvula aórtica, marcando el inicio del proceso de transdiferenciación del endotelio valvular a tejido con capacidad osteogénica. post-print 650 KB