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Lactate: an alternative pathway for the immunosuppressive properties of mesenchymal stem/stromal cells
No full textBackgroundThe metabolic reprogramming of mesenchymal stem/stromal cells (MSC) favoring glycolysis has recently emerged as a new approach to improve their immunotherapeutic abilities. This strategy is associated with greater lactate release, and interestingly, recent studies have proposed lactate as a functional suppressive molecule, changing the old paradigm of lactate as a waste product. Therefore, we evaluated the role of lactate as an alternative mediator of MSC immunosuppressive properties and its contribution to the enhanced immunoregulatory activity of glycolytic MSCs.Materials and methodsMurine CD4+ T cells from C57BL/6 male mice were differentiated into proinflammatory Th1 or Th17 cells and cultured with either L-lactate, MSCs pretreated or not with the glycolytic inductor, oligomycin, and MSCs pretreated or not with a chemical inhibitor of lactate dehydrogenase A (LDHA), galloflavin or LDH siRNA to prevent lactate production. Additionally, we validated our results using human umbilical cord-derived MSCs (UC-MSCs) in a murine model of delayed type 1 hypersensitivity (DTH).ResultsOur results showed that 50 mM of exogenous L-lactate inhibited the proliferation rate and phenotype of CD4+ T cell-derived Th1 or Th17 by 40% and 60%, respectively. Moreover, the suppressive activity of both glycolytic and basal MSCs was impaired when LDH activity was reduced. Likewise, in the DTH inflammation model, lactate production was required for MSC anti-inflammatory activity. This lactate dependent-immunosuppressive mechanism was confirmed in UC-MSCs through the inhibition of LDH, which significantly decreased their capacity to control proliferation of activated CD4+ and CD8+ human T cells by 30%.ConclusionThese findings identify a new MSC immunosuppressive pathway that is independent of the classical suppressive mechanism and demonstrated that the enhanced suppressive and therapeutic abilities of glycolytic MSCs depend at least in part on lactate production
Unraveling patient heterogeneity in complex diseases through individualized co-expression networks: a perspective
No full textThis perspective highlights the potential of individualized networks as a novel strategy for studying complex diseases through patient stratification, enabling advancements in precision medicine. We emphasize the impact of interpatient heterogeneity resulting from genetic and environmental factors and discuss how individualized networks improve our ability to develop treatments and enhance diagnostics. Integrating system biology, combining multimodal information such as genomic and clinical data has reached a tipping point, allowing the inference of biological networks at a single-individual resolution. This approach generates a specific biological network per sample, representing the individual from which the sample originated. The availability of individualized networks enables applications in personalized medicine, such as identifying malfunctions and selecting tailored treatments. In essence, reliable, individualized networks can expedite research progress in understanding drug response variability by modeling heterogeneity among individuals and enabling the personalized selection of pharmacological targets for treatment. Therefore, developing diverse and cost-effective approaches for generating these networks is crucial for widespread application in clinical services
Tunable optical properties of isoreticular UiO-67 MOFs for photocatalysis: a theoretical study
No full textBrazilian autocratic infra-legalism: a response to Kim Lane Scheppele
No full textKim Lane Scheppele claims that “autocratic legalism” is a new form of political authoritarianism, characterized by the use of laws and constitutional engineering. I argue that the Brazilian case provides two counterarguments to this thesis, first refuting the idea that lessons learned from past authoritarianism do not involve the use of law for non-democratic purposes, and then arguing that there are other legal instruments suitable for the implementation of political authori-tarianism besides constitutions and laws. To this end, I divide the article into five parts. First, I sketch the theoretical approach and methodology. Second, I consider a broader literature on the significance of law in non-democratic regimes. Next, I report the importance of the use of law in the Brazilian military dictatorship (1964-1985). Fourth, I explain the use of administrative legal tools in contemporary Brazil and how this use evidences the existence of an “autocratic infra-legalism.” Finally, I present some concluding remarks, and a postscript written in the light of the presidential elections of 2022.Kim Lane Scheppele afirma que el “legalismo autocrático” es una nueva forma de autoritarismo político, caracterizada por el uso de las leyes y la ingeniería constitucional. Sostengo que el caso brasileño proporciona dos contraargumentos a esta tesis, primero refutando la idea de que las lecciones aprendidas del autoriarismo pasado no implican el uso de la ley para fines no democráticos, y después argumentando que hay otros instrumentos legales adecuados para la implement-ación del autoritarismo político además de las constituciones y las leyes. Para ello, divido el artículo en cinco partes. En primer lugar, esbozo el enfoque teórico y la metodología. En segundo lugar, considero una literatura más amplia sobre la im-portancia del derecho en regímenes no democráticos. A continuación, expongo la relevancia del uso del derecho en la dictadura militar brasileña (1964-1985). En cuarto lugar, explico el uso de herramientas jurídicas administrativas en el Brasil contemporáneo y cómo denuncia un "infralegalismo autocrático". Por último, pre-sento algunas observaciones finales y un post-scriptum, a la luz de las elecciones presidenciales de 2022
La traducción audiovisual como estrategia de enseñanza-aprendizaje transversal en un programa de traducción
Get PDFNúmero especial X. Nuevos enfoques y metodologías para la enseñanza de la traducción e interpretación.En el marco de un proyecto de innovación docente y del proceso de actualización curricular del itinerario formativo Traducción Inglés-Español de la UC Temuco, ambos realizados entre 2019 y 2020, se diseñaron e implementaron diversas actividades pedagógicas en torno a la traducción audiovisual. El trabajo tuvo como objetivo principal incorporar temáticas y tecnología de la TAV, con énfasis en la subtitulación, en los cursos teóricos y prácticos del itinerario. Como resultado, se rediseñaron cursos centrales, los de teoría de la traducción, el de tecnología aplicada a la traducción y algunos cursos prácticos de traducción. Así, desde 2020, el estudiantado de nuestro programa recibe formación teórico-práctica en subtitulación como modalidad de TAV. En una segunda instancia, y con base en propuestas como las de Bruti (2016), Díaz-Cintas (2008), Lertola (2015), Talaván (2013), Zabalbeascoa (2012), entre otros, se determinó que el estudio de la TAV en sus diversas modalidades también podría apoyar el desarrollo de otras competencias relacionadas con la traducción —además de la instrumental-profesional y la de transferencia—, como la lingüístico-comunicativa, la sociocultural-extralingüística y la de investigación. Por ello, se incorporaron diversas actividades de enseñanza-aprendizaje en cursos de lengua inglesa, lingüística y terminología.
Concluimos que estas actividades relacionadas con el ejercicio profesional de la TAV han constituido un aporte importante para el desarrollo de competencias y conocimientos en actividades variadas como análisis textuales y discursivos, análisis contrastivos de estrategias de traducción, elaboración de tutoriales para diferentes contextos, y en una reflexión mejor fundamentada de la relevancia de los factores extralingüísticos y culturales en procesos traslativos.Audiovisual translation (AVT), specifically subtitling, has acquired relevance over the years; hence, it was necessary to include it in practical and theoretical courses of our program. Thus, some course syllabuses were redesigned to include AVT in the context of a teaching innovation project (PID2018) carried out by the authors of this article. In the first stage of the program, the new contents were included in courses related to translation theory; subsequently, in the ones dealing with technology applied to translation and a number of practical courses as well. From 2020 on, the students of our translation program learn about subtitling, both at the theoretical and the practical level. Moreover, and based on what we learned from experts such as Bruti (2016), Díaz-Cintas (2008), Lertola (2015), Talaván (2013), Zabalbeascoa (2012), among others, we considered that using subtitling in other courses of the program could be beneficial for the development of other competences related to translator training—besides the instrumental-professional competence—, such as the linguistic-communicative, sociocultural-extralinguistic, and research competences. Hence, a series of teaching/learning activities have been designed and implemented for courses of English, linguistics, and research in translation and terminology. We conclude that the range of activities related to the professional practice of AVT has been a great contribution to the development of competences and the acquisition of knowledge through varied activities such as text and discourse analysis in multimodal texts, contrastive analysis of translation strategies, tutorial production aimed at different contexts and needs, besides a better based reflection on the relevance of sociolinguistic and cultural factors within the process of translation
Modified Unit-Half-Normal Distribution with Applications
No full textIn this article, we introduce a new continuous distribution based on the unit interval. This distribution is generated from a transformation of a random variable with half-normal distribution. We study its basic properties, percentiles, moments and order statistics. Maximum likelihood estimation is applied, and we present a simulation study to observe the behavior of the maximum likelihood estimators. We examine two applications to real proportions datasets, where the new distribution is shown to provide a better fit than other distributions defined in the unit interval
Estrategias profilácticas para disfagia orofaringea en pacientes con cáncer de cabeza y cuello: revisión narrativa
Get PDFEl cáncer de cabeza y cuello es una patología prevalente a nivel mundial. Su abordaje consiste, en buena parte de los casos, de quimiorradioterapia, la cual, dentro de sus múltiples consecuencias, compromete la anatomía y el funcionamiento de órganos relacionadas a la deglución, generando disfagia orofaríngea. En ese sentido, el manejo fonoaudiológico predominantemente se lleva a cabo con ejercicios implementados posterior a la manifestación de la disfagia, con creciente interés sobre el manejo profiláctico del cuadro, existiendo variados estudios sobre la utilidad de ejercicios y maniobras relacionadas. En consecuencia, el objetivo de la presente revisión es presentar recursos terapéuticos basados en evidencia de calidad para el manejo proactivo de esta alteración, orientando la decisión clínica sobre su uso
Simulación Clínica una oportunidad de Aprendizaje Competencial para asignaturas de las Ciencias del Movimiento Humano en carreras de Nutrición y Dietética
No full textLa evolución de la educación superior ha llevado a las universidades a replantearse la forma de enseñar y evaluar, para lo cual han desarrollado un proceso de reforma curricular basado en competencias caracterizado por estar centrado en el aprendizaje de los estudiantes, es así como se han implementado nuevas e innovadoras estrategias de enseñanza aprendizaje que evidencian no solo el contenido teórico sino el desarrollo de habilidades y destrezas que le permiten al estudiante poner en práctica el razonamiento clínico , la resolución de problemas y la comunicación efectiva. Se realizó una búsqueda bibliográfica en idioma español e inglés en base de datos; Scielo, Scopus, PubMed, Redalyc, Educación (JSTOR). El presente artículo tiene como objetivo determinar las bases teóricas e importancia de la aplicación de la simulación clínica en actividades de aprendizaje.The evolution of higher education has led universities to rethink the way of teaching and
evaluating, for which they have developed a process of curricular reform based on competencies
characterized by being focused on student learning, which is how they have been implemented
new and innovative teaching-learning strategies that demonstrate not only the theoretical content
but the development of abilities and skills that allow the student to put into practice clinical
reasoning, problem solving and effective communication. Methodologically, as it is an Essay, a
bibliographic search was conducted in Spanish and English in the database; Scielo, Scopus,
PubMed, Redalyc, Education (JSTOR). The purpose of this paper is to determine the theoretical
bases and importance of the application of clinical simulation in learning activitie
Effectiveness of Whey Protein Supplementation during Resistance Exercise Training on Skeletal Muscle Mass and Strength in Older People with Sarcopenia: A Systematic Review and Meta-Analysis
No full textObjective: To determine the effectiveness of whey protein (WP) supplementation during resistance exercise training (RET) vs. RET with or without placebo supplementation on skeletal muscle mass, strength, and physical performance in older people with Sarcopenia. Methods: Electronic searches in the PubMed, Embase, Scopus, Web of Science, LILACS, SPORTDiscus, Epistemonikos, and CINAHL databases were performed until 20 January 2023. Randomized clinical trials conducted on sarcopenic adults aged 60 or older were included. The studies had to compare the effectiveness of the addition of supplements based on concentrated, isolated, or hydrolyzed whey protein during RET and compare it with RET with or without placebo supplementation on skeletal muscle mass and strength changes. The study selection process, data extraction, and risk of bias assessment were carried out by two independent reviewers. Results: Seven randomized clinical trials (591 participants) were included, and five of them provided data for quantitative synthesis. The overall pooled standardized mean difference (SMD) estimate showed a small effect size in favor of RET plus WP for skeletal muscle mass according to appendicular muscle index, with statistically significant differences compared with RET with or without the placebo group (SMD = 0.24; 95% CI, 0.05 to 0.42; p = 0.01; I-2 = 0%, p = 0.42). The overall pooled mean difference (MD) estimate showed a significant difference of +2.31 kg (MD = 2.31 kg; 95% CI, 0.01 to 4.6; p = 0.05; I-2 = 81%, p < 0.001) in handgrip strength in the RET plus WP group compared with the RET group with or without placebo. The narrative synthesis revealed discordance between the results of the studies on physical performance. Conclusions: WP supplementation during RET is more effective in increasing handgrip strength and skeletal muscle mass in older people with Sarcopenia compared with RET with or without placebo supplementation. However, the effect sizes were small, and the MD did not exceed the minimally important clinical difference. The quality of the evidence was low to very low according, to the GRADE approach. Further research is needed in this field
Physical Pretreatments Applied in Three Commercial Kits for the Extraction of High-Quality DNA from Activated Sewage Sludge
No full textObtaining sufficient and high-quality genomic DNA from sludge samples is a fundamental issue of feasibility and comparability in genomic studies of microbial diversity. Commercial kits for soil are often used for the extraction of gDNA from sludge samples due to the lack of specific kits. However, the evaluation of the performance of commercial kits for sludge DNA extraction is scarce and optimization of these methods to obtain a high quantity and quality of DNA is necessary, especially for downstream genomic sequencing. Sequential batch reactors (SBRs) loaded with lignocellulosic biomass are used for the synthesis of renewable resources such as levulinic acid (LA), adipic acid (AA), and polyhydroxyalkanoates (PHAs), and the biochemical synthesis of these compounds is conducted through the inoculation of microbes present in the residual activated sludge (AS) obtained from a municipal wastewater treatment plant. To characterize these microbes, the extraction of DNA from residual sewage sludge was conducted with three different commercial kits: Nucleospin (R) Soil from Macherey-Nagel, DNEasy (R) PowerSoil (R) from Qiagen, and E.Z.N.A.(R) Plant DNA Kit from Omega BIO-TEK. Nevertheless, to obtain the highest load and quality of DNA for next-generation sequencing (NGS) analysis, different pretreatments and different combinations of these pretreatments were used. The pretreatments considered were an ultrasonic bath and a temperature of 80 degrees C, together and separately with different incubation time periods of 30, 60, and 90 min. The results obtained suggest a significant improvement in the efficiency and quality of DNA extraction with the three commercial extraction kits when used together with the ultrasonic bath and 80 degrees C for 60 min. Here, we were able to prove that physical pretreatments are a viable alternative to chemical lysis for DNA extraction from complex samples such as sludge