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The fatty acid-binding proteins L-BABP and Rep1-NCXSQ bind to anionic lipid membranes by electrostatic interactions. According to Molecular Dynamics (MD) simulations, the interaction of the protein macrodipole with the membrane electric field is a driving force for protein binding and orientation in the interface. To further explore this hypothesis, we studied the interactions of these proteins with cationic lipid membranes. As in the case of anionic lipid membranes, we found that both proteins, carrying a negative as well as a positive net charge, were bound to the positively charged membrane. Their major axis, those connecting the bottom of the β-barrel with the α-helix portal domain, were rotated about 180 degrees as compared with their orientations in the anionic lipid membranes. Fourier transform infrared (FTIR) spectroscopy of the proteins showed that the positively charged membranes were also able to induce conformational changes with a reduction of the β-strand proportion and an increase in α-helix secondary structure. Fatty acid-binding proteins (FABPs) are involved in several cell processes, such as maintaining lipid homeostasis in cells. They transport hydrophobic molecules in aqueous medium and deliver them into lipid membranes. Therefore, the interfacial orientation and conformation, both shown herein to be electrostatically determined, have a strong correlation with the specific mechanism by which each particular FABP exerts its biological function.

Se realizó la descripción del desarrollo de larvas de uno a seis días post-eclosión (dpe), para generar información que ayude a comprender la capacidad alimenticia en etapas tempranas. Las larvas se obtuvieron mediante la inducción hormonal de reproductores, utilizando implantes de análogos sintéticos de GnRH durante la temporada de septiembre-noviembre de 2010. Las muestras fueron incluídas en historesina y teñidas con hematoxilina-eosina. Una vez eclosionada, la larva presenta gran cantidad de vitelo que absorbe gradualmente (1° a 3° dpe). Al 4° dpe, existe una cavidad bucal abierta con estructuras dentales, en este estadio se ha completado el desarrollo ocular, que presenta pigmentación. Se observa la formación de las hendiduras branquiales y se diferencia el intestino en anterior y posterior y se distingue la presencia de vacuolas digestivas en el intestino anterior. En el 5° dpe, se observaron los paquetes de fibras musculares y se distinguió una estructura estomacal. En el 6° dpe, el páncreas, pliegues intestinales y membrana de borde de cepillo son visibles y se observaron partículas de alimento y bacterias dentro del intestino. En base a lo anterior, se concluye que las larvas de D. latifrons han desarrollado completamente el tracto digestivo y órganos asociados que le ayudarán a la búsqueda de alimento, entonces a partir del 4° dpe son capaces de iniciar la alimentación exógena.

El chame es una especie con potencial para la acuicultura en Latinoamérica. Sin embargo, su producción depende de la utilización de individuos juveniles capturados en el medio silvestre, siendo necesaria la reproducción en cautiverio. Objetivo: determinar las condiciones ideales para la obtención de gametos viables y larvas en laboratorio. Métodos: un total de 16 machos y 16 hembras adultos se asignaron a cuatro grupos (n=4) y fueron inyectados con solución salina, Desgly10-Ala6 LHRHa, GnRHa de salmón+domperidone, o con implantes de GnRHa de salmón. Resultados: se logró exitosamente la liberación de esperma para todos los tratamientos. La inducción al desove fue del 100% a las 24 y 48 h para el grupo implantado con GnRHa, 25% para el grupo con LHRHa, y 0% para el grupo GnRHa de salmón+domperidone (48-72 h post-inyección). Conclusiones: el uso de GnRHa y LHRHa es una herramienta útil en la reproducción inducida del chame. Se incluye una descripción morfológica de los oocitos, calidad de esperma y primeros estadio del desarrollo larvario. Se discuten también las condiciones óptimas de salinidad para la fertilización e incubación de huevos fertilizados.O chame é uma espécie com potencial para a aquicultura na América Latina. Porém, toda a produção depende da captura de juvenis selvagens. Objetivo: determinar as condições ideais para a obtenção de gametas viáveis e larvas no laboratório. Métodos: um total de 16 machos e 16 fêmeas adultos foram divididos em quatro grupos (n=4) e foram tratados com injeção de Desgly10Ala6, LHRHa, GnRHa de Salmon+domperidone ou implante de GnRHa de salmão. Resultados: foi possível induzir exitosamente a liberação de esperma com todos os tratamentos. A indução de desove foi do 100% às 24 e 48 h para o grupo implantado com GnRHa, 25% para o tratamento com LHRHa e 0% para o grupo injetado com GnRHa de Salmon+domperidone (48-72 h após-injeção). Conclusões: o uso de GnRHa e LHRHa é uma ferramenta útil na reprodução induzida do chame. Neste trabalho está incluída a descrição dos oócitos, qualidade do esperma e dos estágios iniciais de desenvolvimento larval. Também são abordados os valores ótimos de salinidade, tanto para a fertilização como para a incubação dos ovos fertilizados.The Pacific fat sleeper is a potential species for aquaculture in Latin American countries. Nevertheless, production depends on wildcaught juveniles, thus needing hatchery produced larvae. Objective: the purpose of this study was to determine the ideal conditions for viable gamete release and larvae laboratory production. Methods: a total of 16 mature male and 16 female fish were allocated to one of four groups (n=4) that were injected with either saline solution, Desgly10-Ala6 LHRHa, salmon GnRHa + domperidone, or implanted with salmon GnRHa. Results: spermiation was observed in all treatments. Spawning rates were 100% at 24 and 48 h for the GnRHa implanted group, 25% for the LHRHa group, and 0% for the salmon GnRHa + domperidone group (48-72 h post injection). Conclusion: GnRHa and LHRHa are a succesful tool for chame induced reproduction. A gross morphological description of oocytes, sperm quality, and first stages of larval development is included.

Abstract Introduction Sleep-disordered breathing (SDB) is a major comorbidity in idiopathic pulmonary fibrosis (IPF) and is associated with a poor outcome. There is a lack of knowledge regarding the impact of SDB treatment on IPF. We assessed at one year: (1) the effect of CPAP and/or nocturnal oxygen therapy on IPF regarding lung function, blood mediators, and quality of life; (2) adherence to SDB treatment and SDB changes. Methodology This is a prospective study of consecutive newly diagnosed IPF patients initiating anti-fibrotic treatment. Lung function, polysomnography, blood tests and quality of life questionnaires were performed at inclusion and after one year. Patients were classified as obstructive sleep apnoea (OSA), central sleep apnoea (CSA), and sleep-sustained hypoxemia (SSH). SDB therapy (CPAP and/or nocturnal oxygen therapy) was initiated if needed. Results Fifty patients were enrolled (36% had OSA, 22% CSA, and 12% SSH). CPAP was started in 54% of patients and nocturnal oxygen therapy in 16%. At one-year, polysomnography found improved parameters, though 17% of patients had to add nocturnal oxygen therapy or CPAP, while 33% presented SDB onset at this second polysomnography. CPAP compliance at one year was 6.74 h/night (SD 0.74). After one year, matrix metalloproteinase-1 decreased in OSA and CSA (p = 0.029; p = 0.027), C-reactive protein in OSA (p = 0.045), and surfactant protein D in CSA group (p = 0.074). There was no significant change in lung function. Conclusions Treatment of SBD with CPAP and NOT can be well tolerated with a high compliance. IPF patients may exhibit SDB progression and require periodic re-assessment. Further studies to evaluate the impact of SDB treatment on lung function and serological mediators are needed.

Abstract Objective To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with antisynthetase syndrome and progressive interstitial lung disease (ASS-ILD). Methods Multicentre observational retrospective longitudinal study of a cohort of patients with ASS-ILD that started treatment with RTX due to recurrent or ongoing progressive ILD despite therapy with glucocorticoids and immunosuppressants. Results Twenty-eight patients were analyzed. Examining the entire study population, before treatment with RTX the mean decline in %pFVC and %pDLCO from the ASS-ILD diagnosis to the initiation of RTX treatment (T0) was -6.44% and -14.85%, respectively. After six months of treatment, RTX reversed the decline in pulmonary function test (PFT) parameters: ∆%pFVC +6.29% (95% CI: -10.07 to 2.51; p=0.002 compared to T0) and ∆%pDLCO +6.15% (95% CI: -10.86 to -1.43; p=0.013). Twenty-four patients completed one year of therapy and 22 two years, maintaining the response in PFT: ∆%pFVC: +9.93% (95% CI: -15.61 to -4.25; p=0.002) and ∆%pDLCO: +7.66% (95% CI: -11.67 to -3.65; p

Inmersos en la mirada antropocéntrica, hemos perdido conciencia de nuestro entorno, hemos olvidado que nuestra historia no se puede escribir sin el resto de las especies vivas y que nuestro futuro no podrá darse si no reparamos nuestro vínculo con el planeta. Observar atentamente el mundo que habitamos puede ser un ejercicio amargo, pero necesario si queremos ganar tiempo y ayudar a torcer el rumbo de deterioro ecológico y social del presente. Lo que se da a continuación es el caminar de una búsqueda hacia nuevas formas de afrontar la crisis ecosocial partiendo de la observación del mundo vegetal en tanto inteligencia de la que aprender otras formas de vida, de comunidad, de futuros. El artículo presenta el contexto, el marco reflexivo y el desarrollo de Epífita, un proyecto cultural de investigación y diálogo entre arte y ciencia, relatado desde la experiencia personal que le da origen hasta su primera actividad pública.

Cilj je ovoga rada istražiti perspektivu djece u Hrvatskoj o materijalizmu i vrijednostima koje su važnije od materijalnih dobara. Preciznije, zanima nas smatraju li djeca u Hrvatskoj da je posjedovanje skupih materijalnih dobara i mnogo materijalnih dobara važno, potom koje ishode materijalizma djeca prepoznaju te što smatraju važnijim od posjedovanja skupih stvari i akumuliranja mnogo stvari. Istraživanje je provedenom metodom online fokus-grupa s djecom od 5. do 8. razreda osnovne škole iz različitih dijelova Hrvatske. Uzorak se sastojao od 40 djece (20 dječaka, 20 djevojčica; prosječna dob = 12.85). Analizom izjava djece utvrđeno je da djeca u Hrvatskoj posjedovanje skupih materijalnih dobara i mnogo materijalnih dobara ne smatraju važnim, ali primjećuju da je to bitno nekim pojedincima i društvenim skupinama. Nadalje, djeca s materijalizmom povezuju sljedeće ishode: prihvaćenost u društvu i društveni status, lažne prijatelje i iskorištavanje, kratkotrajnu sreću te, konačno, hvalisanje, aroganciju i bahatost. Kao vrijednosti važnije od materijalnih dobara djeca ističu prijatelje i društvo, obitelj, hobije i osobne interese, zdravlje, sreću i ostalo. U Hrvatskoj dosad nije posebno ispitivana perspektiva djece o materijalizmu. Razumijevanje razmišljanja djece o novcu, potrošnji, bogatstvu, sreći i drugim vrijednostima može pomoći roditeljima, odgojiteljima, donositeljima politika i drugima da bolje podrže dječji razvoj i pruže im vrijednosti koje će im biti korisne u životu.

Introduction: Gram-positive staphylococci are responsible for over 90% of cases of postoperative infectious endophthalmitis, with Staphylococcus epidermidis accounting for approximately 70% of isolated microorganisms. Objective: To evaluate the relationship between S. epidermidis virulence and severity of endophthalmitis in an animal model. Methodology: New Zealand albino rabbits were divided into two groups and administered 100 colony-forming units of S. epidermidis strains. In the virulent group, four rabbits received a multi-antibiotic resistant, mecA, ica, and atlE gene carrying S. epidermidis strain, from a patient´s conjuntival microbiota and three a biofilm-forming S. epidermidis ATCC 35984. In the non-virulent group, five rabbits were inoculated with a strain sensitive to all tested antibiotics and lacking mecA, ica, and atlE genes, also from a patient and three rabbits received the non-producer biofilm S. epidermidis ATCC 29122. Clinical and ultrasound examinations were conducted every three hours until endophthalmitis symptoms appeared, followed by daily clinical assessments. Histological evaluations were performed 15 days post-inoculation. Results: The less virulent group displayed milder inflammation and reduced intraocular damage in comparison to the more virulent group based on clinical and ultrasound observations. Nevertheless, histopathological analysis revealed similar inflammation in all groups, 15 days post-inoculation. Discussion: Less virulent S. epidermidis strains induced less severe inflammation as observed through clinical and ultrasound assessments. However, long-term histopathological assessments showed effects comparable to those seen with the more virulent strain.

Inmersos en la mirada antropocéntrica, hemos perdido conciencia de nuestro entorno, hemos olvidado que nuestra historia no se puede escribir sin el resto de las especies vivas y que nuestro futuro no podrá darse si no reparamos nuestro vínculo con el planeta. Observar atentamente el mundo que habitamos puede ser un ejercicio amargo, pero necesario si queremos ganar tiempo y ayudar a torcer el rumbo de deterioro ecológico y social del presente. Lo que se da a continuación es el caminar de una búsqueda hacia nuevas formas de afrontar la crisis ecosocial partiendo de la observación del mundo vegetal en tanto inteligencia de la que aprender otras formas de vida, de comunidad, de futuros. El artículo presenta el contexto, el marco reflexivo y el desarrollo de Epífita, un proyecto cultural de investigación y diálogo entre arte y ciencia, relatado desde la experiencia personal que le da origen hasta su primera actividad pública. Immersed in the anthropocentric view, we have lost awareness of our environment, we have forgotten that our history cannot be written without the rest of the living species and that our future will not be possible if we do not repair our link with the planet. To observe attentively the world we inhabit can be a bitter exercise, but necessary if we want to gain time and help to turn the course of ecological and social deterioration of the present. What follows is a search for new ways of facing the ecosocial crisis, starting from the observation of the plant world as an intelligence from which to learn other forms of life, of community, of futures. The article presents the context, the reflective framework and the development of Epífita, a cultural project of research and dialogue between art and science, told from the personal experience that gave rise to it to its first public activity.

Sports-related muscle injuries account for 10–55% of all injuries, which is a growing concern, especially given the aging world population. To evaluate the process of skeletal muscle injury and compare it with muscle lesions observed in humans, we developed a novel in vivo model in sheep. In this model, muscle injury was induced by an ultrasound-guided transverse biopsy at the myotendinous junction of the medial gastrocnemius muscle. Twelve male sheep were examined at 3, 7, 14, and 28 days post-injury. Histological, immunofluorescence, and MRI analyses indicate that our sheep model could resemble key human clinicopathological features. Statistically significant differences (p < 0.05) were observed in collagen I, dMHC, α-SMA, and CD68 immunohistochemical detection when comparing injured and healthy muscles. The injured gastrocnemius muscle exhibited elevated levels of type I collagen, infiltration of CD68(+) macrophages, angiogenesis, and the emergence of newly regenerated dMHC(+) myofibers, which persisted for up to 4 weeks post-injury. Similarly, the progression of muscle injury in the sheep model was assessed using advanced clinical 3 T MRI and compared with MRI scans from human patients. The data indicate that the sheep muscle injury model presents features similar to those observed in human skeletal muscle injuries. This makes it a valuable large animal model for studying muscle injuries and developing novel therapeutic strategies.

El presente artículo propone un análisis sobre el impacto del movimiento feminista universitario nucleado en la Red Interuniversitaria por la Igualdad de Género y contra las Violencias (RUGE), del Consejo Interuniversitario Nacional (CIN), en el sistema universitario argentino. Para ello se trabajó con datos cuantitativos provenientes de un diagnóstico sobre la implementación de políticas de género en las instituciones universitarias realizado por la RUGE en 2020. El diagnóstico relevó información de 60 universidades nacionales y provinciales sobre políticas de género y las acciones colectivas para llegar a producir e implementar esas políticas. En relación con los resultados, observamos que el movimiento feminista universitario, en pocos años, pudo generar cambios en las instituciones de educación superior promoviendo protocolos de actuación frente a situaciones de discriminación y violencia de género, capacitaciones sobre la temática en el marco de la “Ley Micaela” y espacios institucionales para garantizar las políticas de género. No obstante, también se detectaron obstáculos relevantes para el crecimiento y promoción de las políticas de género que se podrían traducir en los futuros desafíos de las feministas universitarias.

Tolerance is one of the ideals of a democratic and pluralistic society. It is a way of behaving which allows others the freedom to express opinions with which we do not agree, and the right of others to live according to their principles different from ours. Recently Europe is faced with political challenges caused by mass immigration to European countries. In such circumstances, dilemmas arise regarding the possibility of maintaining the ideals of freedom and equality in European countries, which have become a melting pot of people of different nationalities, races, cultures, religions, and lifestyles. In this article, we used the results of the tolerance research in six European Mediterranean countries, conducted in 2017 as part of the European Values Study project. The objectives were to determine for each of the mentioned countries the level of tolerance or intolerance towards social groups in general, towards individual social groups, and differences between different socio-demographic groups of respondents concerning their level of tolerance or intolerance. The results show that Croatia, Italy, and Slovenia are the countries with the highest tolerance levels compared to the other countries. Also, members of the 'drug addicts' and the 'heavy drinkers' are considered the most problematic social groups in all six European Mediterranean countries. When it comes to gender, there is little difference in tolerance level. More educated and younger respondents have higher levels of tolerance.

Abstract Background Different clinical predictors of physical activity (PA) have been described in idiopathic pulmonary fibrosis (IPF), but studies are lacking evaluating the potential role of muscle strength and anxiety and depression symptoms in PA limitation. Moreover, little is known about the impact of changes in PA in the course of the disease. The aim of the present study was to investigate the relationship between baseline PA and a wide range of variables in IPF, to assess its longitudinal changes at 12 months and its impact on progression free-survival. Methods PA was assessed by accelerometer and physiological, clinical, psychological factors and health-related quality of life were evaluated in subjects with IPF at baseline and at 12 month follow-up. Predictors of PA were determined at baseline, evolution of PA parameters was described and the prognostic role of PA evolution was also established. Results Forty participants with IPF were included and 22 completed the follow-up. At baseline, subjects performed 5765 (3442) daily steps and spent 64 (44) minutes/day in moderate to vigorous PA. Multivariate regression models showed that at baseline, a lower six-minute walked distance, lower quadriceps strength (QMVC), and a higher depression score in the Hospital Anxiety and Depression scale were associated to lower daily step number. In addition, being in (Gender-Age-Physiology) GAP III stage, having a BMI ≥ 25 kg/m2 and lower QMVC or maximum inspiratory pressure were factors associated with sedentary behaviour. Adjusted for age, gender and forced vital capacity (FVC) (%pred.) a lower progression-free survival was evidenced in those subjects that decreased PA compared to those that maintained, or even increased it, at 12 months [HR 12.1 (95% CI, 1.9–78.8); p = 0.009]. Conclusion Among a wide range of variables, muscle strength and depression symptoms have a predominant role in PA in IPF patients. Daily PA behaviour and its evolution should be considered in IPF clinical assessment and as a potential complementary indicator of disease prognosis.

The main aim of this study is to describe the communication between children and parents about children’s desired purchases of items in Croatia. Online focus groups were conducted with children ages 11 to 15, and their parents, using a pre-prepared list of questions. The constant comparative method was applied, and the data were coded thematically, meaning data were organized into groups or codes on the basis of repeating keywords in the transcripts. The analysis shows children mostly ask their parents for clothing items and food. The findings indicate children and parents resolve the purchase decisions based on a few communication themes. Children employ persuasion, bargaining, and negotiation communication to acquire their desired items. As a response, parents employ bargaining and negotiation communication, budgeting and financial communication, usefulness and need communication, and postponed purchase communication. This research contributes to a better understanding of child and parent communication related to child purchase wishes and parent–child communication.

Patellar tendinopathy is a common clinical problem, but its underlying pathophysiology remains poorly understood, primarily due to the absence of a representative experimental model. The most widely used method to generate such a model is collagenase injection, although this method possesses limitations. We developed an optimized rat model of patellar tendinopathy via the ultrasound-guided injection of collagenase mixed with a thermo-responsive Pluronic hydrogel into the patellar tendon of sixty male Wistar rats. All analyses were carried out at 3, 7, 14, 30, and 60 days post-injury. We confirmed that our rat model reproduced the pathophysiology observed in human patients through analyses of ultrasonography, histology, immunofluorescence, and biomechanical parameters. Tendons that were injured by the injection of the collagenase–Pluronic mixture exhibited a significant increase in the cross-sectional area (p < 0.01), a high degree of tissue disorganization and hypercellularity, significantly strong neovascularization (p < 0.01), important changes in the levels of types I and III collagen expression, and the organization and presence of intra-tendinous calcifications. Decreases in the maximum rupture force and stiffness were also observed. These results demonstrate that our model replicates the key features observed in human patellar tendinopathy. Collagenase is evenly distributed, as the Pluronic hydrogel prevents its leakage and thus, damage to surrounding tissues. Therefore, this model is valuable for testing new treatments for patellar tendinopathy.

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El objetivo de esta investigación es caracterizar el estado actual de la cultura tributaria, a nivel global, e identificar el desarrollo de la cultura tributaria en Colombia. Al respecto, se desarrolló un análisis bibliométrico a partir de la base de datos Scopus, utilizando la herramienta Bibliometrix y, como complemento, se hizo una revisión sistemática cualitativa ejecutando el protocolo Prisma. Entre los años del 2006 y 2021 se encontraron 53 artículos científicos a nivel global. En el año 2021 se generó el mayor incremento en la producción científica. Sin embargo, en la revisión sistemática de la literatura se identificaron 8 documentos que describen diferentes herramientas y estrategias que tienen como finalidad fomentar la cultura tributaria en Colombia. Los resultados del análisis bibliométrico determinan que existe una escasa producción científica del tema abordado. Se concluye que se deben fortalecer los procesos investigativos relacionados con la cultura tributaria, no solo en Colombia sino a nivel global.

Zelda Fitzgerald has remained under Scott Fitzgerald’s shadow for too long. It was not until the seventies that scholars such as Nancy Milford started to focus on her life and works. Since then, interest in Zelda has done nothing but increase. Recent biographies, articles, and novels about Zelda represent the need to place her in the spotlight by focusing not only on her life and her tumultuous marriage to Scott Fitzgerald, but also on her artistic career as a writer, dancer, and painter. During her short life, Zelda tried to find her own voice, despite her husband’s opposition and her frequent hospitalizations in different mental institutions. This article seeks to explore Zelda’s growth from flapper to writer in order to highlight her self-determination to become a renowned and independent artist.

Since the use of digital technology (DT) has become a significant part of children’s and parents’ everyday life, one of the main questions is why and for what purposes children use DT. This paper aims to explore categories of motivation for DT use among Croatian children aged 9 to 15 years, and their rate of occurrence, from the perspective of children (18 boys; 13 girls; average age = 11) and their parents (3 fathers; 28 mothers) during the COVID-19 pandemic. Focus groups with children as well as their parents were conducted online via Zoom, from March 30th to May 5th 2021. Results show that both children and their parents state following motives for children’s use of DT: fun and entertainment, interaction and communication, relaxation and rest, learning and seeking information. Furthermore, children, but not their parents, state as their motives time pass and boredom, and Fear of Missing Out. This research contributes to a better understanding of the reasons why children use DT devices, provides a taxonomy of motives and shows that children’s motives for DT use are universal to different life circumstances.

BackgroundRecent studies have shown the presence of SARS-CoV-2-specific antibodies in the milk of breastfeeding mothers vaccinated with mRNA and convalescent. However, limited information is available in lactating women receiving other vaccine platforms used in developing countries, such as the inactivated SARS-CoV-2 vaccine BBIBP-CorV (Sinopharm) and the non-replicating adenovirus vaccines Sputnik V (Gamaleya Institute) and ChAdOx1-S (Oxford AstraZeneca).MethodsHere, we evaluated anti-SARS-CoV-2 IgG and IgA levels in both serum and milk samples using a longitudinal and a cross-sectional cohort of 208 breastfeeding vaccinated women from Argentina with or without previous SARS-CoV-2 infection.ResultsThe analysis showed that IgA levels remain constant in serum and milk of breastfeeding mothers between the first and second doses of vector-based vaccines (Sputnik V and ChAdOx1-S). After the second dose, anti-spike IgA was found positive in 100% of the serum samples and in 66% of breastmilk samples. In addition, no significant differences in milk IgA levels were observed in participants receiving BBIBP-CorV, Sputnik V or ChAdOx1-S. IgG levels in milk increased after the second dose of vector-based vaccines. Paired longitudinal samples taken at 45 and 120 days after the second dose showed a decrease in milk IgG levels over time. Study of IgA levels in serum and milk of vaccinated naïve of infection and vaccinated-convalescent breastfeeding participants showed significantly higher levels in vaccinated-convalescent than in participants without previous infection.ConclusionThis study is relevant to understand the protection against SARS-CoV-2 by passive immunity in newborns and children who are not yet eligible to receive vaccination.