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Bacille Calmette-Guérin (BCG) vaccination can confer nonspecific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. We show that mice vaccinated intravenously with BCG exhibited reduced weight loss and/or improved viral clearance when challenged with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 B.1.351) or PR8 influenza. Protection was first evident between 14 and 21 d post-vaccination and lasted â¼3 months. Notably, BCG induced a biphasic innate response and robust antigen-specific type 1 helper T cell (TH1 cell) responses in the lungs. MyD88 signaling was essential for innate and TH1 cell responses, and protection against SARS-CoV-2. Depletion of CD4+ T cells or interferon (IFN)-γ activity before infection obliterated innate activation and protection. Single-cell and spatial transcriptomics revealed CD4-dependent expression of IFN-stimulated genes in lung myeloid and epithelial cells. Notably, BCG also induced protection against weight loss after mouse-adapted SARS-CoV-2 BA.5, SARS-CoV and SHC014 coronavirus infections. Thus, BCG elicits integrated organ immunity, where CD4+ T cells feed back on tissue myeloid and epithelial cells to imprint prolonged and broad innate antiviral resistance.
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Inmunidad Adaptativa , Vacuna BCG , Animales , Ratones , Humanos , Retroalimentación , Vacunación , Pérdida de Peso , Antivirales , Inmunidad InnataRESUMEN
Second Life (SL) is an online virtual world with a social environment that may serve as a valuable learning supplement to traditional preclinical teaching methods. The educational advantages of this virtual world include immersion and interactivity. The aim of this study was to compare the efficacy of using 3-dimensional interactive platforms (3DIPs) designed in SL to that of traditional teaching methods for developing students' understanding of dental clinical situations that are difficult to simulate in real life. For this study, 3DIPs were developed to compare the acquisition of 3 learning objectives: understanding concepts, procedural aspects of interaction with the patient, and spatial interpretation of anatomical structure interactions. A representative dental topic, the use of a semiadjustable articulator, was selected. A quasi-experimental design with 2 groups and pretest-posttest comparison was used. The students in the control group received the conventional teaching established for the subject, which does not include SL experiences. The students in the experimental group received conventional instruction and had access to all 3DIPs for 4 weeks without limitation. The pretest and posttest consisted of a multiple-choice test with 20 questions. A Student t test was used to compare the test results of the groups (significance level α = 0.05). The posttest scores for the understanding of concepts and spatial interpretation were significantly higher in the experimental group than in the control group (P < 0.05). However, there was no statistically significant difference between groups in posttest scores on the topic of procedural aspects. Students who used cooperative methods for acquisition of knowledge were observed to be highly motivated. The results suggest that the SL environment helps students to understand anatomical interactions that are difficult to observe in real life, is attractive to students, and contains tools with high didactic potential.
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Educación en Odontología , Realidad Virtual , Odontología , Educación en Odontología/métodos , Evaluación Educacional , Humanos , AprendizajeRESUMEN
PURPOSE: Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks effective diagnostic and therapeutic options. Membrane type 1 matrix metalloproteinase (MT1-MMP) is an attractive biomarker for improving patient selection. This study aimed to develop a theranostic tool using a highly tumour-selective anti-MT1-MMP antibody (LEM2/15) radiolabelled with 89Zr for PET and 177Lu for therapy in a TNBC murine model. METHODS: The LEM2/15 antibody and IgG isotype control were radiolabelled with 89Zr. PET imaging was performed in a TNBC orthotopic mouse model at 1, 2, 4, and 7 days after administration. Tissue biodistribution and pharmacokinetic parameters were analysed and Patlak linearisation was used to calculate the influx rate of irreversible uptake. The TNBC mice were treated with [177Lu]Lu-DOTA-LEM2/15 (single- or 3-dose regimen) or saline. Efficacy of [177Lu]Lu-DOTA-LEM2/15 was evaluated as tumour growth and DNA damage (γH2AX) in MDA 231-BrM2-831 tumours. RESULTS: At 7 days post-injection, PET uptake in tumour xenografts revealed a 1.6-fold and 2.4-fold higher tumour-to-blood ratio for [89Zr]Zr-Df-LEM2/15 in the non-blocked group compared to the blocked and IgG isotype control groups, respectively. Specific uptake of LEM2/15 in TBNC tumours mediated by MT1-MMP-binding was demonstrated by the Patlak linearisation method, providing insights into the potential efficacy of LEM2/15-based treatments. A similar uptake was found for [89Zr]Zr-Df-LEM2/15 and [177Lu]Lu-DOTA-LEM2/15 in tumours 7 days post-injection (6.80 ± 1.31 vs. 5.61 ± 0.66 %ID/g). Tumour doubling time was longer in the [177Lu]Lu-DOTA-LEM2/15 3-dose regimen treated group compared to the control (50 vs. 17 days, respectively). The percentage of cells with γH2AX-foci was higher in tumours treated with [177Lu]Lu-DOTA-LEM2/15 3-dose regimen compared to tumours non-treated or treated with [177Lu]Lu-DOTA-LEM2/15 single-dose (12 % vs. 4-5 %). CONCLUSIONS: The results showed that the 89Zr/177Lu-labelled anti-MT1-MMP mAb (LEM2/15) pair facilitated immune-PET imaging and reduced tumour growth in a preclinical TNBC xenograft model.
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Bipolar plates (BPs) are one of the most important components of polymer electrolyte membrane fuel cells (PEMFCs) because of their important role in gas and water management, electrical performance, and mechanical stability. Therefore, promising materials for use as BPs should meet several technical targets established by the United States Department of Energy (DOE). Thus far, in the literature, many materials have been reported for possible applications in BPs. Of these, polymer composites reinforced with carbon allotropes are one of the most prominent. Therefore, in this review article, we present the progress and critical analysis on the use of carbon material-reinforced polymer composites as BPs materials in PEMFCs. Based on this review, it is observed that numerous polymer composites reinforced with carbon allotropes have been produced in the literature, and most of the composites synthesized and characterized for their possible application in BPs meet the DOE requirements. However, these composites can still be improved before their use for BPs in PEMFCs.
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Both protein nanoparticle and mRNA vaccines were clinically de-risked during the COVID-19 pandemic1-6. These vaccine modalities have complementary strengths: antigen display on protein nanoparticles can enhance the magnitude, quality, and durability of antibody responses7-10, while mRNA vaccines can be rapidly manufactured11 and elicit antigen-specific CD4 and CD8 T cells12,13. Here we leverage a computationally designed icosahedral protein nanoparticle that was redesigned for optimal secretion from eukaryotic cells14 to develop an mRNA-launched nanoparticle vaccine for SARS-CoV-2. The nanoparticle, which displays 60 copies of a stabilized variant of the Wuhan-Hu-1 Spike receptor binding domain (RBD)15, formed monodisperse, antigenically intact assemblies upon secretion from transfected cells. An mRNA vaccine encoding the secreted RBD nanoparticle elicited 5- to 28-fold higher levels of neutralizing antibodies than an mRNA vaccine encoding membrane-anchored Spike, induced higher levels of CD8 T cells than the same immunogen when delivered as an adjuvanted protein nanoparticle, and protected mice from vaccine-matched and -mismatched SARS-CoV-2 challenge. Our data establish that delivering protein nanoparticle immunogens via mRNA vaccines can combine the benefits of each modality and, more broadly, highlight the utility of computational protein design in genetic immunization strategies.
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Portland cement (PC) is a material that is indispensable for satisfying recent urban requirements, which demands infrastructure with adequate mechanical and durable properties. In this context, building construction has employed nanomaterials (e.g., oxide metals, carbon, and industrial/agro-industrial waste) as partial replacements for PC to obtain construction materials with better performance than those manufactured using only PC. Therefore, in this study, the properties of fresh and hardened states of nanomaterial-reinforced PC-based materials are reviewed and analyzed in detail. The partial replacement of PC by nanomaterials increases their mechanical properties at early ages and significantly improves their durability against several adverse agents and conditions. Owing to the advantages of nanomaterials as a partial replacement for PC, studies on the mechanical and durability properties for a long-term period are highly necessary.
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Several studies performed on human subjects have examined the effects of adolescent cannabis consumption on brain structure or function using brain imaging techniques. However, the evidence from these studies is usually heterogenous and affected by several confounding variables. Animal models of adolescent cannabinoid exposure may help to overcome these difficulties. In this exploratory study, we aim to increase our understanding of the protracted effects of adolescent Δ9-tetrahydrocannabinol (THC) in rats of both sexes using magnetic resonance (MR) to obtain volumetric data, assess grey and white matter microstructure with diffusion tensor imaging (DTI) and measure brain metabolites with 1H-MR spectroscopy (MRS); in addition, we studied brain function using positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-glucose as the tracer. THC-exposed rats exhibited volumetric and microstructural alterations in the striatum, globus pallidus, lateral ventricles, thalamus, and septal nuclei in a sex-specific manner. THC administration also reduced fractional anisotropy in several white matter tracts, prominently in rostral sections, while in vivo MRS identified lower levels of cortical choline compounds. THC-treated males had increased metabolism in the cerebellum and olfactory bulb and decreased metabolism in the cingulate cortex. By contrast, THC-treated females showed hypermetabolism in a cluster of voxels comprising the entorhinal piriform cortices and in the cingulate cortex. These results indicate that mild THC exposure during adolescence leaves a lingering mark on brain structure and function in a sex-dependant manner. Some of the changes found here resemble those observed in human studies and highlight the importance of studying sex-specific effects in cannabinoid research.
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Cannabinoides , Dronabinol , Ratas , Animales , Masculino , Humanos , Femenino , Adolescente , Dronabinol/farmacología , Dronabinol/metabolismo , Ratas Wistar , Imagen de Difusión Tensora , Encéfalo , Cannabinoides/farmacologíaRESUMEN
Comparar la distancia de los contactos interoclusales, en máxima intercuspidación, respecto al eje central de premolares y molares, en dos grupos, con y sin abfracciones. Materiales y métodos. La población estuvo conformada por 91 estudiantes de la asignatura de Oclusión de la Facultad de Odontología de la Universidad de San Martín de Porres, de la cual se obtuvo una muestra de 1230 dientes entre premolares y molares, a los cuales se les registró los contactos interoclusales en máxima intercuspidación con un papel articular Accu film II, para determinar la ubicación del contacto; se midió la distancia entre el contacto y el surco central por medio de una sonda periodontal. Posteriormente, se determinó la presencia o ausencia de abfracciones en los dientes analizados y se contrastaron las mediciones entre ambos grupos. Resultados. Luego de analizar los promedios de las distancias de los contactos oclusales con respecto al surco central, por medio de la prueba t de Student, se encontró diferencias significativas en las distancias de los dientes con y sin abfracciones. Conclusiones. Este estudio arroja evidencia que apoya a la teoría de la flexión dental como etiología de este tipo de lesiones, ya que muestra que existe una mayor distancia del contacto oclusal respecto al eje central del diente, en los dientes que presentaron dichas lesiones...
To compare the distance of interocclusal contacts, in maximum intercuspation, regarding the central axis of premolars and molars in two groups, with and without abfractions. Materials and methods. The population consisted of 91 students of thecourse of Occlusion, Faculty of Dentistry, University of San Martin de Porres, from which a sample of 1230 teeth between premolars and molars was obtained, to which interocclusal contacts in maximum intercuspation were registered with articulating paper Accu II film to determine the location of the contact; the distance between the contact and the central groove by a periodontal probe was measured. Subsequently, the presence or absence of teeth abfractions analyzed and measurements were compared between groups was determined. Results. After analyzing the average of distances of occlusal contacts to the central sulcus, by the Student t test, significant differences in the distances of the teeth without abfractions was found. Conclusions. This study provides evidence that supports the theory of dental bending as etiology of this type of injury, as it shows that there is a greater distance from the occlusal contact with the central axis of the tooth, in those teeth with these lesions...
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Humanos , Masculino , Adolescente , Femenino , Atrición Dental , Diente Molar , Diente Premolar , Oclusión Dental , Epidemiología Descriptiva , Estudios Transversales , Estudios Observacionales como AsuntoRESUMEN
En el presente trabajo se utilizaron 18 ratones (Wistar) distribuídos en 3 ratones por cada grupo experimental (24 horas, 3,7,14, 28 Y 90 días); estos animales fueron sometidos a una exposición pulpar, de los primeros molares superiores e inmediato recubrimiento con dos pastas a base de iodoformo, paramonoclorofeno alcanforado y Rifocort, además de hidróxido de calcio y óxido de zinc como productos modificadores en la pasta denominada como "experimental". Luego de los correspondientes procedimientos laboratoriales y obtención de los cortes histológicos para el estudio al microscopio de luz se pudo concluir que de una forma general las dos pastas son bien toleradas en el tejido conjuntivo de la pulpa de dientes de ratones.
In this reseach 18 rats (Wistar strain) were used divided in 3 animals for each experimental period of time previusly stabilited as 24 hours, 3, 7, 14, 28 and 90 days. In these animals a pulpal exposure was practicede the in upper first molars followed by imediat pulp capping with the paste being now proposed (experimental paste) or with one suggent by Guedes-Pinto &. Cols, 1981 (control paste). After the experimental times elapred the animals were sacrificed and have their maxillae extracted for 7 um thick slides be made amd were dyed by means hematoxilin and eosin technique to be examined at the ligtht miscroscope. From the histologic examination was posible to conlude tha both pastes were well tolerated by the conective pulpal tissue of the rat molars, since a discreta inflatory reaction was found for time intervals of 24 hours and 3 days. For the 7 days observation period the initial formation of dentin bridge was seen that at op days was completely forme up to well as the periapical tissue have shown histologig characterristics of normality. The reseach has shown that the addition of calcium hydoxide and zinc oxide to the control paste did not modify the histo-pathology reactions of rats pulpal tissue.
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Animales , Ratones , Pulpa Dental/patología , Diente Primario , Pastas de DientesRESUMEN
Os autores descrevem um caso clínico de epidermólise bolhosa simples e tecem breves comentários sobre a classificação, detendo-se nas diversas modalidades terapêuticas, com particular ênfase no tratamento preventivo