Mycobacterium bovis BCG expressing the proteins CP40 or CP09720 of Corynebacterium pseudotuberculosis promotes protection in mice after challenge.

In this study, we assessed the survival and immune response of mice vaccinated with recombinant Mycobacterium bovis BCG Pasteur that expressed the CP40 or CP09720 proteins after the mice were challenged with a C. pseudotuberculosis MIC-6 virulent strain. Six groups of mice (n = 10 mice per group) were immunised with a sterile 0.9% saline solution (G1), 106 CFU of M. bovis BCG Pasteur (G2), 106 CFU of M. bovis BCG/cp40 (G3), 106 CFU of M. bovis BCG/cp09720 (G4), M. bovis BCG/cp40 boosted with rCP40 (G5), and M. bovis BCG/cp09720 boosted with rCP09720 (G6). The highest survival rate of 90% was observed in the G5 group, followed by 80% in the G6 group and 70% in the G3 and G4 groups. Moreover, a significantly greater induction of IFN-γ and IL-10 was found in the G3 group and higher IL-17 levels were recorded in the G5 group compared to their levels in the control group (G1) (p < 0.05). A specific humoral immune response (total IgG) was found in the G5 and G6 groups on day 42 compared to the level of response in the G1 group. These results indicated that the vector vaccine elicited significantly greater survival of mice in all experimental groups after a strong virulent challenge and induced a strong immune response.

Dual targeting of MAPK and PI3K pathways unlocks redifferentiation of Braf-mutated thyroid cancer organoids.

Thyroid cancer is the most common endocrine malignancy and several genetic events have been described to promote the development of thyroid carcinogenesis. Besides the effects of specific mutations on thyroid cancer development, the molecular mechanisms controlling tumorigenesis, tumor behavior, and drug resistance are still largely unknown. Cancer organoids have been proposed as a powerful tool to study aspects related to tumor development and progression and appear promising to test individual responses to therapies. Here, using mESC-derived thyroid organoids, we developed a BrafV637E-inducible model able to recapitulate the features of papillary thyroid cancer in vitro. Overexpression of the murine BrafV637E mutation, equivalent to BrafV600E in humans, rapidly triggers to MAPK activation, cell dedifferentiation, and disruption of follicular organization. BrafV637E-expressing organoids show a transcriptomic signature for p53, focal adhesion, ECM-receptor interactions, EMT, and inflammatory signaling pathways. Finally, PTC-like thyroid organoids were used for drug screening assays. The combination of MAPK and PI3K inhibitors reversed BrafV637E oncogene-promoted cell dedifferentiation while restoring thyroid follicle organization and function in vitro. Our results demonstrate that pluripotent stem cells-derived thyroid cancer organoids can mimic tumor development and features while providing an efficient tool for testing novel targeted therapies.

"Existe o espaço, mas ao mesmo tempo não existe": análise do processo de cuidado no tratamento psicofarmacológico na saúde mental / "Existe el espacio, pero al mismo tiempo no existe": análisis del proceso de cuidado en el tratamiento psicofarmacéutico en la salud mental / "There is space, but at the same time there isn't": the care process analysis in psychopharmacological treatment in mental health

Considerando os desafios à reabilitação psicossocial, objetivou-se compreender a perspectiva de usuários e trabalhadores no tratamento psicofarmacológico. Trata-se de um estudo qualitativo que entrevistou seis profissionais e dez usuários do Centro de Atenção Psicossocial de um município da região norte de Minas Gerais. As transcrições foram tratadas em Ciclos de Codificação e examinadas pela Análise de Discurso. Definiram-se três categorias relativas à dimensão micropolítica do cuidado: o fluxograma institucional, os espaços intercessores e a produção subjetiva dos agentes. Revelaram-se dissonâncias entre enunciados alusivos à política da atenção psicossocial, com a concorrência de concepções e tecnologias de cuidado emancipatórias e restritivas. Constatou-se a importância da análise micropolítica do cuidado no tratamento psicofarmacológico, favorecendo os processos de contratualidade, protagonismo e autonomia do usuário.

Considerando los desafíos para la rehabilitación psicosocial, el objetivo fue comprender la perspectiva de usuarios y trabajadores en el tratamiento psicofarmacéutico. Se trata de un estudio cualitativo que entrevistó a seis profesionales y a diez usuarios del Centro de Atención Psicosocial de un municipio de la región norte de Minas Gerais. Las transcripciones fueron tratadas en Ciclos de Codificación y examinadas por el Análisis del Discurso. Se definieron tres categorías relativas a la dimensión micropolítica del cuidado: el diagrama de flujo institucional, los espacios intercesores y la producción subjetiva de los agentes. Se revelaron disonancias entre enunciados alusivos a la política de la atención psicosocial, con la concurrencia de concepciones y tecnologías de cuidado emancipatorias y restrictivas. Se constató la importancia del análisis micropolítico del cuidado en el tratamiento psicofarmacéutico, favoreciendo los procesos de contractualidad, protagonismo y autonomía del usuario.

Considering the challenges to psychosocial rehabilitation, this study was aimed at understanding the perspective of users and workers regarding psychopharmacological treatment. This is a qualitative study, which interviewed six providers and ten users of the Psychosocial Care Center of a municipality in the north of Minas Gerais. The transcripts were treated in Coding Cycles and examined by Discourse Analysis. Three categories related to the micropolitical dimension of care were defined: the institutional flowchart; the intercessory spaces; and the subjective production of the agents. Dissonances were revealed between statements alluding to the psychosocial care policy, with the competition of emancipatory and restrictive conceptions and technologies of care. The importance of the micropolitical analysis of care in psychopharmacological treatment was verified, favoring the processes of contractuality, protagonism, and user autonomy.

Global loss of cellular m6A RNA methylation following infection with different SARS-CoV-2 variants.

Insights into host-virus interactions during SARS-CoV-2 infection are needed to understand COVID-19 pathogenesis and may help to guide the design of novel antiviral therapeutics. N 6-Methyladenosine modification (m6A), one of the most abundant cellular RNA modifications, regulates key processes in RNA metabolism during stress response. Gene expression profiles observed postinfection with different SARS-CoV-2 variants show changes in the expression of genes related to RNA catabolism, including m6A readers and erasers. We found that infection with SARS-CoV-2 variants causes a loss of m6A in cellular RNAs, whereas m6A is detected abundantly in viral RNA. METTL3, the m6A methyltransferase, shows an unusual cytoplasmic localization postinfection. The B.1.351 variant has a less-pronounced effect on METTL3 localization and loss of m6A than did the B.1 and B.1.1.7 variants. We also observed a loss of m6A upon SARS-CoV-2 infection in air/liquid interface cultures of human airway epithelia, confirming that m6A loss is characteristic of SARS-CoV-2-infected cells. Further, transcripts with m6A modification are preferentially down-regulated postinfection. Inhibition of the export protein XPO1 results in the restoration of METTL3 localization, recovery of m6A on cellular RNA, and increased mRNA expression. Stress granule formation, which is compromised by SARS-CoV-2 infection, is restored by XPO1 inhibition and accompanied by a reduced viral infection in vitro. Together, our study elucidates how SARS-CoV-2 inhibits the stress response and perturbs cellular gene expression in an m6A-dependent manner.

Transplantable human thyroid organoids generated from embryonic stem cells to rescue hypothyroidism.

The thyroid gland captures iodide in order to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism, which is one of the most common disorder in humans and is not always satisfactorily treated by lifelong hormone replacement. Therefore, in addition to the lack of in vitro tractable models to study human thyroid development, differentiation and maturation, functional human thyroid organoids could pave the way to explore new therapeutic approaches. Here we report the generation of transplantable thyroid organoids derived from human embryonic stem cells capable of restoring plasma thyroid hormone in athyreotic mice as a proof of concept for future therapeutic development.

A close shave: How SARS-CoV-2 induces the loss of cilia.

Wang et al. report in this issue (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202108015) that the SARS-CoV-2 protein ORF10 increases the activity of the E3 ligase CUL2ZYG11B, leading to the degradation of multiple ciliary proteins. The resulting loss of cilia may facilitate the spread of SARS-CoV-2 in the respiratory tree.

Green algae (Viridiplantae) in sediments from three lakes on Vega Island, Antarctica, assessed using DNA metabarcoding.

BACKGROUND: Vega Island is located off the eastern tip of the Antarctic Peninsula (Maritime Antarctica), in the Weddell Sea. In this study, we used metabarcoding to investigate green algal DNA sequence diversity present in sediments from three lakes on Vega Island (Esmeralda, Copépodo, and Pan Negro Lakes). METHODS AND RESULTS: Total DNA was extracted and the internal transcribed spacer 2 region of the nuclear ribosomal DNA was used as a DNA barcode for molecular identification. Green algae were represented by sequences representing 78 taxa belonging to Phylum Chlorophyta, of which 32% have not previously been recorded from Antarctica. Sediment from Pan Negro Lake generated the highest number of DNA reads (11,205), followed by Esmeralda (9085) and Copépodo (1595) Lakes. Esmeralda Lake was the richest in terms of number of taxa (59), with Copépodo and Pan Negro Lakes having 30 taxa each. Bray-Curtis dissimilarity among lakes was high (~ 0.80). The Order Chlamydomonadales (Chlorophyceae) gave the highest contribution in terms of numbers of taxa and DNA reads in all lakes. The most abundant taxon was Chlorococcum microstigmatum. CONCLUSIONS: The study confirms the utility of DNA metabarcoding in assessing potential green algal diversity in Antarctic lakes, generating new Antarctic records.

Effects of DOC addition from different sources on phytoplankton community in a temperate eutrophic lake: An experimental study exploring lake compartments.

A mesocosm experiment was conducted in a temperate eutrophic lake with the hypotheses: 1) the addition of a labile form of DOC would trigger a more pronounced response in phytoplankton biomass and composition compared with a non-labile form; 2) DOC addition would increase phytoplankton biomass by co-inserting organic nutrients for phytoplankton growth; 3) DOC addition would change phytoplankton composition, in particular towards mixotrophic taxa due to higher DOC availability; and that 4) there would be differences in phytoplankton responses to DOC addition, depending on whether sediment was included or not. We used two types of mesocosms: pelagic mesocosms with closed bottom, and benthic mesocosms open to the sediment. The experiment ran for 29 days in total. The DOC addition occurred once, at Day 1. Besides the control, there were two treatments: HuminFeed® (non-labile DOC) at a concentration of 2 mg L-1, and a combination of 2 mg L-1 HuminFeed® and 2 mg L-1 DOC from alder leaf leachate (labile). Responses were detected only in the treatment with alder leaf extract. Ecosystem processes responded immediately to DOC addition, with the fall in dissolved oxygen and pH indicating an increase in respiration, relative to primary production (Day 2). In contrast, there was a delay of a few days in structural responses in the phytoplankton community (Day 6). Phytoplankton biomass increased after DOC addition, probably boosted by the phosphorus released from alder leaf extract. Changes in phytoplankton composition towards mixotrophic taxa were not as strong as changes in biomass, and happened only in the pelagic mesocosms. With the DOC addition, diatoms prevailed in benthic mesocosms, while the contribution of colonial buoyant cyanobacteria increased in the pelagic ones. This study points towards the necessity to look in greater detail at specific responses of phytoplankton to DOC concentration increases considering lake-habitat and sediment influence.

Sistema de recomendaciones sobre la evaluación de proyectos de desarrollo de software / System of Recommendations on the Evaluation of Software Development Projects

Introducción: En la actualidad existen organizaciones que asumen como estructura un modelo de gestión por proyectos. El creciente número de proyectos que se conceptualizan y se desarrollan, genera gran cúmulo de datos. Sin embargo, la insuficiente capacidad de análisis y procesamiento sobre los datos generados, imposibilitan la identificación de información que facilite la toma de decisiones a los principales directivos. Objetivo: La presente investigación propone el desarrollo de un Sistema de recomendación que integra la Sumarización Lingüística de Datos (LDS). Materiales y métodos: En la investigación se destaca la utilización de métodos de la investigación científica empíricos y teóricos; a través del análisis histórico-lógico se revelaron las investigaciones asociadas al uso de LDS para la construcción de explicaciones de las recomendaciones. Se utilizó encuesta para corroborar la satisfacción de los usuarios en cuanto a la síntesis de la información almacenada en el repositorio de datos. Resultados: Las recomendaciones generadas aumentan la posibilidad de que los usuarios interpreten los datos almacenados a partir de la integración con explicaciones constituidas por resúmenes lingüísticos. Conclusiones: El sistema obtenido fue valorado como muy bueno para ser aplicado al problema de toma de decisiones sobre la evaluación de proyectos en centros de desarrollo de software(AU)

Introduction: Currently there are organizations that assume a project management model as a structure. The increasing number of projects that are conceptualized and developed generates a large accumulation of data. However, the insufficient capacity for analysis and processing of the data generated makes it impossible to identify information that facilitates decision-making for the main managers. Objective: This research proposes the development of a recommendation system that integrates the Linguistic Data Summarization (LDS). Materials and methods: The research highlights the use of empirical and theoretical scientific research methods. Through the historical-logical analysis, the investigations associated with the use of LDS for the construction of explanations of the recommendations were revealed. A survey was used to corroborate user satisfaction regarding the synthesis of the information stored in the data repository. Results: The generated recommendations increase the possibility that the users interpret the stored data from the integration with explanations constituted by linguistic summaries. Conclusions: The obtained system was valued as very good to be applied to the decision-making problem on the evaluation of projects in software development centers(AU)

A Comparison of Two-Dimensional and Three-Dimensional Techniques for Kinematic Analysis of the Sagittal Motion of Sheep Hindlimbs During Walking on a Treadmill.

Compared to rodents, sheep offer several attractive features as an experimental model for testing different medical and surgical interventions related to pathological gait caused by neurological diseases and injuries. To use sheep for development of novel treatment strategies in the field of neuroscience, it is key to establish the relevant kinematic features of locomotion in this species. To use sheep for development of novel treatment strategies in the field of neuroscience, it is crucial to understand fundamental baseline characteristics of locomotion in this species. Despite their relevance for medical research, little is known about the locomotion in the ovine model, and next to nothing about the three-dimensional (3D) kinematics of the hindlimb. This study is the first to perform and compare two-dimensional (2D) and 3D hindlimb kinematics of the sagittal motion during treadmill walking in the ovine model. Our results show that the most significant differences took place throughout the swing phase of the gait cycle were for the distal joints, ankle and metatarsophalangeal joint, whereas the hip and knee joints were much less affected. The results provide evidence of the inadequacy of a 2D approach to the computation of joint kinematics in clinically normal sheep during treadmill walking when the interest is centered on the hoof's joints. The findings from the present investigation are likely to be useful for an accurate, quantitative and objective assessment of functionally altered gait and its underlying neuronal mechanisms and biomechanical consequences.

Single-Cell Trajectory Inference Guided Enhancement of Thyroid Maturation In Vitro Using TGF-Beta Inhibition.

The thyroid gland regulates metabolism and growth via secretion of thyroid hormones by thyroid follicular cells (TFCs). Loss of TFCs, by cellular dysfunction, autoimmune destruction or surgical resection, underlies hypothyroidism. Recovery of thyroid hormone levels by transplantation of mature TFCs derived from stem cells in vitro holds great therapeutic promise. However, the utilization of in vitro derived tissue for regenerative medicine is restricted by the efficiency of differentiation protocols to generate mature organoids. Here, to improve the differentiation efficiency for thyroid organoids, we utilized single-cell RNA-Seq to chart the molecular steps undertaken by individual cells during the in vitro transformation of mouse embryonic stem cells to TFCs. Our single-cell atlas of mouse organoid systematically and comprehensively identifies, for the first time, the cell types generated during production of thyroid organoids. Using pseudotime analysis, we identify TGF-beta as a negative regulator of thyroid maturation in vitro. Using pharmacological inhibition of TGF-beta pathway, we improve the level of thyroid maturation, in particular the induction of Nis expression. This in turn, leads to an enhancement of iodide organification in vitro, suggesting functional improvement of the thyroid organoid. Our study highlights the potential of single-cell molecular characterization in understanding and improving thyroid maturation and paves the way for identification of therapeutic targets against thyroid disorders.

Práticas educativas de genitores e professores e repertório comportamental infantil / Educational practices of parents and teachers and children's behavioral repertoire

O objetivo deste estudo é descrever, a partir de múltiplos instrumentos e informantes, o repertório comportamental (habilidades sociais e problemas de comportamento) de quatro crianças de 6 a 7 anos, duas de cada sexo, e as práticas educativas positivas (habilidades sociais educativas) e negativas de quatro mães, quatro pais e duas professoras dos primeiros anos do Ensino Fundamental. Foram utilizados na coleta de dados instrumentos de relato e protocolo de observação de interações genitores-criança a partir de situação de brincadeira. Os resultados reafirmam que práticas positivas estão relacionadas à baixa frequência de problemas de comportamento e presença de habilidades sociais e, ao contrário, práticas negativas estão relacionadas a problemas de comportamento. A literatura tem encontrado tais relações entre pais e filhos e com a presente pesquisa nota-se o mesmo no que se refere à interação professor-aluno.

The aim of this study is to describe, from multiple instruments and informants, the behavioral repertoire (social skills and behavioral problems) of four children aged six to seven years old, two of each sex, and positive educational practices (educational social skills) and negative practices of four mothers, four fathers and two teachers from the first years of elementary school. Data collection instruments and protocol for observing the parent-child interactions, from a situation of play, were used. The results reaffirm that positive practices are related to the low frequency of behavioral problems and the presence of social skills, and, on the contrary, negative practices are related to behavioral problems. The literature has found such relationships between parents and children and with the present research the same can be noticed with regard to teacher-student interaction.

Two-dimensional and three-dimensional techniques for determining the kinematic patterns for hindlimb obstacle avoidance during sheep locomotion / Técnicas bidimensionais e tridimensionais para determinar os padrões cinemáticos durante a ultrapassagem de obstáculos pelos membros pélvicosdurante a locomoção de ovinos

ABSTRACT: Analysis of locomotion is often used as a measure for impairment and recovery following experimental peripheral nerve injury. Compared to rodents, sheep offer several advantages for studying peripheral nerve regeneration. In the present study, we compared for the first time, two-dimensional (2D) and three-dimensional (3D) hindlimb kinematics during obstacle avoidance in the ovine model. This study obtained kinematic data to serve as a template for an objective assessment of the ankle joint motion in future studies of common peroneal nerve (CP) injury and repair in the ovine model. The strategy used by the sheep to bring the hindlimb over a moderately high obstacle, set to 10% of its hindlimb length, was pronounced knee, ankle and metatarsophalangeal flexion when approaching and clearing the obstacle. Despite the overall time course kinematic patterns about the hip, knee, ankle, and metatarsophalangeal were identical, we found significant differences between values of the 2D and 3D joint angular motion. Our results showed that the most apparent changes that occurred during the gait cycle were for the ankle (2D-measured STANCEmax: 157±2.4 degrees vs. 3D-measured STANCEmax: 151±1.2 degrees; P<.05) and metatarsophalangeal joints (2D-measured STANCEmin: 151±2.2 degrees vs. 3D-measured STANCEmin: 162 ± 2.2 degrees; P<.01 and 2D-measured TO: 163±4.9 degrees vs. 3D-measured TO: 177±1.4 degrees; P<.05), whereas the hip and knee joints were much less affected. Data and techniques described here are useful for an objective assessment of altered gait after CP injury and repairin an ovine model.

RESUMO: A análise da locomoção é frequentemente usada como uma medida para avaliar a disfunção e sua recuperação após lesão nervosa periférica experimental. Quando comparadas com os roedores, as ovelhas oferecem várias características atrativas como modelo experimental para o estudo da regeneração nervosa periférica. Não existem estudos acerca dos resultados da locomoção após lesão e reparação do nervo periférico no modelo ovino. No presente estudo, realizámos e comparámos a cinemática bidimensional (2D) e, pela primeira vez, tridimensional (3D) do membro pélvico durante a ultrapassagem de obstáculos no modelo ovino. Este estudo teve como objetivo obter dados cinemáticos para servir de modelo para uma avaliação objetiva do movimento articular do tornozelo em estudos futuros de lesão e reparação do nervo fibular comum (FC) no modelo ovino. A estratégia usada pelas ovelhas para elevar o membro pélvico sobre um obstáculo com uma altura moderada, fixado em 10% do seu comprimento, caracteriza-se por uma flexão pronunciada do joelho, tornozelo e metatarso-falangeana ao se aproximar e ultrapassar o obstáculo. Apesar dos padrões cinemáticos do quadril, joelho, tornozelo e metatarso-falangeano terem sido idênticos, foram encontradas diferenças significativas entre os valores do movimento angular das articulações em 2D e 3D. Os nossos resultados mostram que as mudanças mais aparentes que ocorreram durante o ciclo da marcha foram nas articulações do tornozelo (em 2DSTANCEmax: 157±2.4 graus vs. em 3D STANCEmax: 151±1.2 graus; P<.05) e metatarso-falangeana (em 2D STANCEmin: 151±2.2 graus vs. em 3D STANCEmin: 162 ± 2.2 graus; P<.01 e em 2D TO: 163±4.9 graus vs. em 3D TO: 177±1.4 graus; P<.05), enquanto as articulações do quadril e do joelho foram muito menos afetadas. É provável que os dados e técnicas descritas aqui sejam úteis para uma avaliação objetiva das alterações na marcha após lesão e reparação do PC no modelo ovino.

Sistema de Laboratorios Remoto para el estudio de la Microbiología y Parasitología Médica / Remote Laboratory System for the study of Medical Microbiology and Parasitology

Introducción: como parte del proceso de formación de enfermeros, médicos y tecnólogos de la salud son habilitados temas relacionados con la microbiología. Sin embargo, a partir del conjunto de medidas de seguridad y la disponibilidad de recursos físicos, no es posible el estudio de diversos microorganismos. Objetivo: desarrollar un Sistema de Laboratorios Remoto para la práctica de Microbiología y Parasitología Médica. Materiales y métodos: el sistema de Laboratorios Remoto posee un microscopio electrónico controlado mediante una interface de comunicación con un ordenador conectado a la red. Resultados: se obtuvo como resultado un Sistema de Laboratorios Remoto que puede ser accedido mediante Internet o la red institucional. Facilita el estudio y la interpretación de diferentes muestras biológicas. Brinda un conjunto de reportes y estadísticas que permiten realizar análisis históricos de comportamiento. Conclusiones: a partir del desarrollo de las prácticas de laboratorios a distancia, es posible el estudio de diferentes microorganismos sin riesgos biológicos para el estudiante(AU)

Introduction: as part of the training process for nurses, physicians and health technologists, topics related to microbiology are enabled. However, based on the set of security measures and the availability of physical resources, the study of various microorganisms is not possible. Objective: to develop a Remote Laboratory System for the practice of the subject Medical Microbiology and Parasitology. Methods: the Remote Laboratory System has an electronic microscope controlled by a communication interface with a computer connected to the network. Results: a Remote Laboratory System that can be accessed through the Internet or the institutional network. The system facilitates the study and interpretation of different biological samples and also provides a set of reports and statistics that allow for historical behavior analysis. Conclusions: from the development of remote laboratory practices, it is possible to study different microorganisms without biological risks for the student(AU)

Sistema de apoyo al diagnóstico médico de COVID-19 mediante mapa cognitivo difuso / Support system to Covid-19 medical diagnosis via diffuse cognitive map

Introducción: Los escenarios de convivencia de las diversas poblaciones son muy complejos, lo que contribuye con la propagación de enfermedades. Diagnosticar tempranamente enfermedades infecciosas representa una tarea fundamental para disminuir su propagación y evitar epidemias. Sin embargo, la inconsistencia en los datos de poblaciones y la imposibilidad de contar con un diagnóstico oportuno en muchos casos trae como consecuencia la proliferación de pandemias tales como la COVID-19. Objetivo: Desarrollar un sistema de apoyo al diagnóstico médico para COVID-19 a partir de la modelación de las relaciones causales de los criterios de diagnóstico, para conformar el mapa cognitivo difuso. Métodos: Para el desarrollo de la investigación se utilizaron métodos teóricos, empíricos y estadísticos, tales como: analítico-sintético, inductivo-deductivo, hipotético-deductivo, modelación. Como método empírico se utilizó la entrevista semiestructurada con la intención de recoger información que permitiera incluir contenidos no prescritos y precisar el conocimiento de los expertos sobre los principales indicadores para la toma de decisiones en el diagnóstico médico de la COVID-19. Resultados: El sistema funciona a través de un mapa cognitivo difuso para modelar las relaciones causales que representan la base de la inferencia. Se utilizan técnicas de inteligencia artificial como base al diagnóstico médico. Se presenta un ejemplo demostrativo para el diagnóstico médico de la COVID-19 en el que se modelan las relaciones causales de los diferentes conceptos que describen la enfermedad provocada. Conclusiones: El sistema diseñado constituye una herramienta viable de apoyo a la toma de decisiones en el diagnóstico médico de la COVID-19, que permite obtener criterios evaluativos a partir de la modelación de las relaciones causales, esto lo hace extensible a otros tipos de situaciones de emergencias sanitarias(AU)

Introduction: Different populations coexistence scenarios are very complex, which contributes to the spread of diseases. Diagnosing infectious diseases early is a critical task in reducing its spread and preventing epidemics. However, inconsistency in population data and the inability to have timely diagnosis in many cases result in the proliferation of pandemics such as COVID-19. Objective: Develop a support system for COVID-19 medical diagnostic from modeling causal relations of diagnostic criteria, to form the diffuse cognitive map. Methods: Theoretical, empirical and statistical methods were used for the development of the research, such as: analytical-synthetic, inductive-deductive, hypothetical-deductive, modeling. As an empirical method, the semi-structured interview was used with the intention of collecting information that would include unprescribed contents and require expert knowledge of the main indicators for decision-making in COVID-19 medical diagnosis. Results: The system works through a diffuse cognitive map to model causal relationships that represent the inference´s basis. Artificial intelligence techniques are used as a basis for medical diagnosis. A demonstrative example is presented for COVID-19 medical diagnosis in which are modelled the causal relations of the different concepts that the disease describes. Conclusions: The designed system is a viable support tool for decision-making in COVID-19 medical diagnosis, which allows to obtain evaluative criteria from the modelling of causal relations, and this makes it extendable to other types of health emergencies situations(AU)

Método para evaluar el desempeño de los recursos humanos en proyectos médicos mediante computación con palabras / Method for Evaluating the Performance of Human Resources in Medical Projects by Computing with Words

Introducción: el proceso de evaluación del desempeño de los recursos humanos en proyectos médicos está sujeto a niveles considerables de subjetividad, lo cual genera incertidumbre a la hora de tomar decisiones. Problemas de esta índole donde se incluye la evaluación y clasificación de alternativas en el proceso, pueden ser abordados a través de la Computación con palabras. Objetivo: el objetivo del presente trabajo es desarrollar un método para la evaluación del desempeño de los recursos humanos en proyectos médicos mediante computación con palabras. Materiales y métodos: se utilizan los conjuntos de datos lingüísticos para mejorar la interpretación de los resultados. Se emplea el modelo de representación de la información lingüística basado en 2-tuplas en el tratamiento de la incertidumbre. El procesamiento de la información se realizó mediante los operadores de agregación de información Promedio Ponderado Ordenado que permiten la agregación de información de acuerdo a parámetros predefinidos obteniéndose un valor representativo. Resultados: se obtiene un método de apoyo a la toma de decisiones basado en la computación con palabras. El método propuesto fue implementado para manejar la incertidumbre existente en el proceso de evaluación del desempeño de los recursos humanos en proyectos médicos a partir de la evaluación y clasificación de alternativas, basado en computación con palabras. Conclusiones: la implementación del método propuesto, permite evaluar y clasificar a los Recursos Humanos según su desempeño(AU)

Introduction: the process of evaluating the performance of human resources in medical projects is subject to considerable levels of subjectivity, which generates uncertainty when making decisions. Problems of this nature, where the evaluation and classification of alternatives is included in the process, can be addressed through Computing with Words. Objective: to develop a method for evaluating the performance of human resources in medical projects using Computing with Words. Method: linguistic data sets are used to improve the interpretation of the results. The 2-tuple-based linguistic information representation model is used in the treatment of uncertainty. The information processing was performed using the Ordered Weighted Average information aggregation operators that allow the aggregation of information according to predefined parameters obtaining a representative value. Results: a method of decision support is obtained, based on Computing with Words. The method was implemented to manage the uncertainty in the process of evaluating the performance of human resources in medical projects based on the evaluation and classification of alternatives. Conclusions: the implementation of the proposed method allows evaluating and classifying human resources according to their performance(AU)

NanH and PknG putative virulence factors as a recombinant subunit immunogen against Corynebacterium pseudotuberculosis infection in mice.

Despite the economic and zoonotic relevance of caseous lymphadenitis, a competent immunoprophylaxis tool is still necessary. Here, we evaluated two putative virulence factors of Corynebacterium pseudotuberculosis, rNanH, and rPknG, as recombinant subunit vaccines in a murine model against the infection by C. pseudotuberculosis. Three groups of ten Balb/c mice each were inoculated with a sterile 0.9% saline solution (G1), rNanH (G2), or rPknG (G3) in formulations containing saponin as an adjuvant. The mice received two vaccine doses intercalated by a 21-day interval and were challenged with 2 × 104 CFU/mL of the C. pseudotuberculosis MIC-6 strain 21 days after the last immunization. The total IgG, IgG1, and IgG2a production levels increased significantly in the experimental groups (G2 and G3) on day 42. The highest levels of IgG2a antibodies in G2 and G3 were observed compared to IgG1 levels. G3 showed a significant (p < 0.05) humoral response through higher production of total IgG at day 42 when compared to G2. A significant increase of mRNA expression levels of interleukin (IL)-17, tumor necrosis factor, and interferon-γ was observed only in G2, while IL-4 was significantly produced only by G3. The levels of IL-10 and IL-12 obtained were not significant in any group. The survival rates after the challenge were 20% for G3 and 60% for G2 (p < 0.05). Our findings suggest that the formulation containing rNanH and saponin (G2) resulted in the best protection against the challenge and was able to elicit a Th1 immune response in mice, and can be considered as a promising antigen in the development of an effective vaccine against caseous lymphadenitis.

IMPACT OF ACUTE KIDNEY INJURY STAGING ON PROGNOSIS OF PATIENTS WITH CIRRHOSIS.

BACKGROUND: Acute kidney injury (AKI) is a common and severe complication of cirrhosis. OBJECTIVE: To evaluate the impact of AKI staging on 30-day mortality of patients with cirrhosis. METHODS: We performed a retrospective cohort study of hospitalized patients with cirrhosis. Acute kidney injury (AKI) was diagnosed according to the International Club of Ascites recommendations and staged according to the European Association for the Study of the Liver guidelines. Comparisons between groups were made by one-way analysis of variance and Tukey test. Chi-square was calculated for dichotomous variables. Comparisons of renal impairment status among patients were performed using Kaplan-Meier statistics and differences between groups were analyzed using the log-rank test. A P-value <0.05 was considered to be statistically significant. RESULTS: Two hundred and thirty-two patients were included in the study. The diagnosis of AKI was performed in 98 (42.2%) of them. The overall 30-day mortality was 19.8% (46/232). Mortality increased as the degree of AKI progressed. Among patients who did not have AKI, mortality was 5.2% (7/134). When compared to patients without AKI, patients diagnosed with AKI stage 1a had mortality of 12.1% (4/33, P=0.152); patients with AKI stage 1b had mortality of 45% (18/40, P<0.001); and patients with AKI stages 2 or 3 had mortality of 68% (17/25, P<0.001). Moreover, it is noteworthy that full response to treatment was associated to a decreased mortality when compared to patients who did not show complete recovery of renal function (14.3% vs 57.9%, P<0.001). CONCLUSION: AKI stages 1b or greater, but not AKI stage 1a, are associated to higher 30-day mortality of patients with cirrhosis.

Avaliação prognóstica de lesão renal aguda em pacientes cirróticos / Impact of acute kidney injury staging on prognosis of patients with cirrhosis

ABSTRACT BACKGROUND: Acute kidney injury (AKI) is a common and severe complication of cirrhosis. OBJECTIVE: To evaluate the impact of AKI staging on 30-day mortality of patients with cirrhosis. METHODS: We performed a retrospective cohort study of hospitalized patients with cirrhosis. Acute kidney injury (AKI) was diagnosed according to the International Club of Ascites recommendations and staged according to the European Association for the Study of the Liver guidelines. Comparisons between groups were made by one-way analysis of variance and Tukey test. Chi-square was calculated for dichotomous variables. Comparisons of renal impairment status among patients were performed using Kaplan-Meier statistics and differences between groups were analyzed using the log-rank test. A P-value <0.05 was considered to be statistically significant. RESULTS: Two hundred and thirty-two patients were included in the study. The diagnosis of AKI was performed in 98 (42.2%) of them. The overall 30-day mortality was 19.8% (46/232). Mortality increased as the degree of AKI progressed. Among patients who did not have AKI, mortality was 5.2% (7/134). When compared to patients without AKI, patients diagnosed with AKI stage 1a had mortality of 12.1% (4/33, P=0.152); patients with AKI stage 1b had mortality of 45% (18/40, P<0.001); and patients with AKI stages 2 or 3 had mortality of 68% (17/25, P<0.001). Moreover, it is noteworthy that full response to treatment was associated to a decreased mortality when compared to patients who did not show complete recovery of renal function (14.3% vs 57.9%, P<0.001). CONCLUSION: AKI stages 1b or greater, but not AKI stage 1a, are associated to higher 30-day mortality of patients with cirrhosis.

RESUMO CONTEXTO: A lesão renal aguda (LRA) é uma complicação comum e grave na cirrose. OBJETIVO: Avaliar o impacto dos estágios da LRA na mortalidade em 30 dias de pacientes com cirrose. MÉTODOS: Realizou-se um estudo de coorte retrospectivo com pacientes com cirrose hospitalizados. LRA foi diagnosticada de acordo com as recomendações do International Club of Ascites e o estadiamento foi feito de acordo com as recomendações da European Association for the Study of the Liver. Comparações entre os grupos foram feitas por análise de variância unidirecional e teste de Tukey. O teste do qui-quadrado foi calculado para variáveis categóricas. Comparações quanto à lesão renal entre os pacientes foram realizadas com estatísticas de Kaplan-Meier, e diferenças entre os grupos foram analisadas pelo teste de log-rank. Um P-valor <0,05 foi considerado estatisticamente significativo. RESULTADOS: Duzentos e trinta e dois pacientes foram incluídos no estudo. O diagnóstico de LRA foi realizado em 98 (42,2%) deles. A mortalidade geral em 30 dias foi de 19,8% (46/232). A mortalidade aumentou de acordo com a progressão dos estágios de LRA. Entre pacientes sem LRA, a mortalidade foi de 5,2% (7/134). Quando comparados aos pacientes sem LRA, pacientes diagnosticados com LRA estágio 1a tiveram mortalidade de 12,1% (4/33, P=0,152); pacientes com LRA estágio 1b tiveram mortalidade de 45% (18/40, P<0,001); e pacientes com LRA estágios 2 ou 3 tiveram mortalidade de 68% (17/25, P<0,001). Além disso, é importante ressaltar que a resposta completa ao tratamento associou-se à menor mortalidade quando comparada à ausência de recuperação completa da função renal (14,3% vs 57,9%, P<0,001). CONCLUSÃO: LRA estágios 1b ou superior, mas não estágio 1a, estão associadas à maior mortalidade em 30 dias de pacientes com cirrose.

Cell viability analysis of Toxocara cati larvae with LIVE / DEAD® Viability/Cytotoxicity kit.

Toxocara spp. are responsible for causing toxocariasis, a zoonotic disease of global significance. In some countries of South America, toxocariasis is considered the most prevalent human helminthic infection. The objective of this study was to evaluate LIVE/DEAD® Viability/Cytotoxicity kit as an alternative method to analyze the viability of Toxacara cati larvae. Two control groups were used to confirm the usage of this methodology: 100 untreated T. cati larvae as a negative control (G1) and 100 T. cati larvae killed by thermal shock as a positive control (G2). Subsequently, the viability of T. cati larvae was assessed by the exclusion of the trypan blue dye and by LIVE/DEAD® Viability/Cytotoxicity kit, as well as observation of motility and morphology. In order to confirm the larvicidal effect, T. cati larvae G1 and G2 were inoculated in mice to evaluate their progression in vivo. As expected, G1 showed negative staining by Trypan blue and was stained green by LIVE/DEAD® Viability/Cytotoxicity kit in all the exposure periods. Moreover, G1 presented 100% of relative motility (RM) (score of 5). G2 group was stained blue by Trypan blue and red by LIVE/DEAD® Viability/Cytotoxicity kit, and had 0% RM (score zero) in 24 h of incubation period. In mice, G2 was not viable and, therefore, was not able to infect the animals. In mice inoculated with G1, however, larvae were recovered from all the evaluated organs, except eyes. These results demonstrate that the viability of T. cati larvae was accurately obtained by the LIVE/DEAD® Viability/Cytotoxicity kit, making it an alternative method for viability evaluation.