ABSTRACT Background: The coronavirus disease (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus and is responsible for nearly 6 million deaths worldwide in the past 2 years. Machine learning (ML) models could help physicians in identifying high-risk individuals. Objectives: To study the use of ML models for COVID-19 prediction outcomes using clinical data and a combination of clinical and metabolic data, measured in a metabolomics facility from a public university. Methods: A total of 154 patients were included in the study. “Basic profile” was considered with clinical and demographic variables (33 variables), whereas in the “extended profile,” metabolomic and immunological variables were also considered (156 characteristics). A selection of features was carried out for each of the profiles with a genetic algorithm (GA) and random forest models were trained and tested to predict each of the stages of COVID-19. Results: The model based on extended profile was more useful in early stages of the disease. Models based on clinical data were preferred for predicting severe and critical illness and death. ML detected trimethylamine N-oxide, lipid mediators, and neutrophil/lymphocyte ratio as important variables. Conclusion: ML and GAs provided adequate models to predict COVID-19 outcomes in patients with different severity grades.

Abstract: 1. Objective. Analyze the relationship between stakeholders, environmental proactivity and small mezcal business performance in the state of Oaxaca, Mexico. 2) Method: a non-experimental and transversal statistical work was carried out based on a structured questionnaire and a sample of 100 businesses. 3) Results. The study showed that environmental planning, environmental awareness and clients have a positive influence on business performance. 4) Study limitations / Implications. With a larger sample, statistical techniques could be used to provide a more complete picture of the relationship between the variables analyzed. 5) Originality / Value. This research is one of the first works in analyzing environmental proactivity in the small mezcal businesses in Oaxaca, Mexico. 6). Findings and Conclusions. Environmental proactivity is the variable that mediates the effect of stakeholders on performance, when the literature indicates otherwise. 7). Implications. The context and types of businesses provide new insights for the theory and strategic alternatives that seek to improve organizational performance.

Resumen: 1) Objetivo. Analizar la relación entre stakeholders, proactividad ambiental y desempeño de negocios mezcaleros en Oaxaca, México. 2) Método: trabajo estadístico no experimental y transversal con base en un cuestionario estructurado y una muestra de 100 negocios. 3) Resultados. La planificación ambiental, la concienciación ambiental y los clientes influyen positivamente sobre el desempeño. 4) Limitaciones del estudio/Implicaciones. Con una muestra más grande, podrían utilizarse técnicas estadísticas que proporcionen un panorama más completo de la relación entre las variables analizadas. 5) Originalidad/Valor. Esta investigación es uno de los primeros trabajos en analizar la proactividad ambiental en negocios mezcaleros. 6). Hallazgos y Conclusiones. La proactividad ambiental es la variable que media el efecto de los stakeholders sobre el desempeño, cuando la literatura indica lo contrario. 7). Implicaciones. El contexto y tipo de negocios brinda nuevos elementos para la teoría y alternativas estratégicas que buscan mejorar el desempeño organizacional.

Abstract INTRODUCTION: Biomarkers are critical tools for finding new approaches for controlling the spread of tuberculosis (TB), including for predicting the development of TB therapeutics, vaccines, and diagnostic tools. METHODS: Expression of immune biomarkers was analyzed in peripheral blood cells stimulated and non-stimulated with M. tuberculosis antigens ESAT-6, CFP10 and TB7.7. in Warao indigenous individuals. These biomarkers may be able to differentiate TB states, such as active tuberculosis (ATB) cases and latent tuberculosis infection (LTBI) from non-infected controls (NIC). A real-time reverse transcription polymerase chain reaction (RT-qPCR) assay was performed on 100 blood samples under non-stimulation or direct ex vivo conditions (NS=50) and stimulation conditions (S=50). RESULTS: The findings are shown as the median and interquartile range (IQR) of relative gene expression levels of IFN-γ, CD14, MMP9, CCR5, CCL11, CXCL9/MIG, and uPAR/PLAUR immune biomarkers. MMP9 levels were significantly higher in the LTBI-NS and LTBI-S groups compared with the NIC-NS and NIC-S groups. However, CCR5 levels were significantly lower in the LTBI-S group compared with both NIC-NS and NIC-S groups. CCL11 levels were significantly lower in the LTBI-S group compared with the NIC-NS group. CONCLUSIONS: Preliminary findings showed that MMP9 immune biomarkers separated LTBI indigenous individuals from NIC indigenous individuals, while CCR5, CCL11, CD14, and IFN-γ did not differentiate TB states from NIC. MMP9 may be useful as a potential biomarker for LTBI and new infected case detection among Warao indigenous individuals at high risk of developing the disease. It may also be used to halt the epidemic, which will require further validation in larger studies.

BACKGROUND Once in the pulmonary alveoli, Mycobacterium tuberculosis (Mtb) enters into contact with alveolar macrophages and dendritic cells (DCs). DCs represent the link between the innate and adaptive immune system owing to their capacity to be both a sentinel and an orchestrator of the antigen-specific immune responses against Mtb. The effect that the virulence of Mtb has on the interaction between the bacilli and human DCs has not been fully explored. OBJECTIVE To evaluate the effect of Mtb virulence on human monocyte-derived DCs. METHODS We exposed human monocyte-derived DCs to Mtb clinical strains (isolated from an epidemiological Mtb diversity study in Mexico) bearing different degrees of virulence and evaluated the capacity of DCs to internalise the bacilli, control intracellular growth, engage cell death pathways, express markers for activation and antigen presentation, and expand to stimulate autologous CD4+ T cells proliferation. FINDINGS In the case of the hypervirulent Mtb strain (Phenotype 1, strain 9005186, lineage 3), we report that DCs internalise and neutralise intracellular growth of the bacilli, undergo low rates of apoptosis, and contribute poorly to T-cell expansion, as compared to the H37Rv reference strain. In the case of the hypovirulent Mtb strain (Phenotype 4, strain 9985449, lineage 4), although DCs internalise and preclude proliferation of the bacilli, the DCs also display a high level of apoptosis, massive levels of apoptosis that prevent them from maintaining autologous CD4+ T cells in a co-culture system, as compared to H37Rv. MAIN CONCLUSIONS Our findings suggest that variability in virulence among Mtb clinical strains affects the capacity of DCs to respond to pathogenic challenge and mount an immune response against it, highlighting important parallels to studies previously done in mouse models.

BACKGROUND Type 2 diabetes (T2D) is a risk factor for the development of tuberculosis (TB), although the associated mechanisms are not known. OBJECTIVES To study the association between T2D and the basal phenotype of macrophages, and their immune response to Mycobacterium tuberculosis (Mtb) infection. METHODS We evaluated the influence of T2D on the response of monocyte-derived macrophages (MDM) to Mtb in patients with T2D (n = 10) compared to healthy subjects (n = 9), before and after infection with Mtb clinical isolates bearing different degrees of virulence. The levels of cell surface markers for activation secreted cytokines and chemokines, bacterial association, and intracellular bacterial growth were evaluated. FINDINGS The expression levels of HLA-DR, CD80, and CD86 were low while those of of PD-L1 were high in uninfected MDMs derived from patients with diabetes; as a result of Mtb infection, changes were only observed in the expression levels of PD-L1. The levels of cytokines (e.g., IL-6, IL-1β, IL-10, and IL-12) and chemokines (e.g., MCP-1, MIG, and RANTES) are perturbed in MDMs derived from patients with diabetes, both before infection and in response to Mtb infection. In response to the more virulent Mtb strains, the levels of association and bacterial clearance were diminished in MDMs derived from patients with diabetes. CONCLUSIONS T2D affects the basal activation state of the macrophages and its capacity to respond and control Mtb infection.

Abstract Introduction: Entrepreneurial orientation (EO) has been widely recognized in the strategic management field, because it represents a key factor to obtain a better performance. Entrepreneurial oriented firms are monitoring its environment, making innovations, taking risks, searching for opportunities, anticipating to the customer needs and responding to the aggressive actions from its competence. The object of this research is to analyze the relationship between the EO and the firm performance in the Mexican handcraft sector. Method: This research was cross-sectional with the application of a survey to 170 Mexican artisans from Oaxaca, Guerrero, Puebla and Tlaxcala. The exploratory factorial analysis was used to test the validity of the scale; the reliability was test by the Cronbach’s Alpha coefficient. In order to test the five hypothesis of the research model, a bivariate correlation analysis and a linear regression analysis was made among all the research variables. Results: Results show that innovativeness, proactiveness and aggressive competitiveness are the variables that are related positively and directly with the financial and non-financial performance of the handcraft business in Mexico. Discussion or Conclusion: This paper could be one of the first research in analyze the performance in handcraft businesses under the EO focus. It gives some opportunities in the research field: a deeper analysis of each variable, to test the EO scale in other kind of businesses and sectors, a better conceptualization and operationalization of variables in order to make much more detailed statistical analysis, and determinate exactly the effect of the OE variables in the firm performance.

Resumen Introducción: En el campo de la administración estratégica la orientación emprendedora ha sido ampliamente reconocida ya que es un ingrediente importante para que las empresas obtengan un buen desempeño. Las empresas con orientación emprendedora están constantemente monitoreando su ambiente y son las primeras en realizar innovaciones y como consecuencia de esto, toman riesgos, buscan oportunidades, tratan de anticiparse a las demandas de los clientes y participan iniciando o respondiendo a las acciones agresivas de la competencia. El objetivo de esta investigación es analizar la relación entre la orientación emprendedora y el desempeño de los negocios del sector de artesanías en México. Método: Se llevó a cabo un trabajo de estadístico no experimental y transversal con base en un cuestionario estructurado dirigido a 170 dueños de negocios de artesanía en Oaxaca, Guerrero, Puebla y Tlaxcala. Para probar la validez de las escalas se utilizó el Análisis Factorial Exploratorio y la confiabilidad fue probada mediante la determinación de los coeficientes del Alfa de Cronbach. Y para probar las hipótesis de la investigación se realizó un análisis de correlación bivariada y el análisis de regresión lineal múltiple. Resultados: Los resultados mostraron que la innovatividad, la proactividad y la agresividad competitiva son las variables que se relacionaron positiva y significativamente con el desempeño tanto financiero como no financiero. Discusión o Conclusión: Al ser esta investigación una de las primeras en analizar el desempeño de los negocios de artesanía bajo el enfoque de orientación emprendedora proporciona oportunidades de investigación: analizar de manera más profunda cada una de las variables; la escala de medición necesita ser probada en otros sectores similares al artesanal, como pueden ser las empresas comunitarias, pequeñas agroindustrias de alimentos, etc., y realizar una mejor conceptualización y operacionalización de variables para poder llegar a hacer análisis estadísticos mucho más detallados que permitan determinar con mayor exactitud los efectos de las variables en el desempeño de las empresas.

It has been reported that patients with progressive tuberculosis (TB) express abundant amounts of the antimicrobial peptides (AMPs) cathelicidin (LL-37) and human neutrophil peptide-1 (HNP-1) in circulating cells, whereas latent TB infected donors showed no differences when compared with purified protein derivative (PPD) and QuantiFERON®-TB Gold (QFT)-healthy individuals. The aim of this study was to determine whether LL-37 and HNP-1 production correlates with higher tuberculin skin test (TST) and QFT values in TB household contacts. Twenty-six TB household contact individuals between 26-58 years old TST and QFT positive with at last two years of latent TB infection were recruited. AMPs production by polymorphonuclear cells was determined by flow cytometry and correlation between TST and QFT values was analysed. Our results showed that there is a positive correlation between levels of HNP-1 and LL-37 production with reactivity to TST and/or QFT levels. This preliminary study suggests the potential use of the expression levels of these peptides as biomarkers for progression in latent infected individuals.

La infección por VIH (virus de la inmunodeficiencia humana) en la actualidad es un grave problema de salud pública a nivel mundial, que requiere de nuevas estrategias vacunales para detener su propagación así como para su efectivo tratamiento. Algunos estudios relacionados con la inmunidad innata en contra de VIH, han demostrado que los péptidos antimicrobianos (AMP´s) pueden generar resistencia a las infecciones virales. En la presente revisión, se describen a los péptidos antimicrobianos de humano y su actividad en contra de VIH así como péptidos de otras especies como plantas, anfibios, insectos y varias especies de animales que poseen un potencial terapéutico o profiláctico en la infección por VIH. Se describen brevemente algunos mecanismos mediante los cuales estos péptidos pueden bloquear la replicación e infección por el VIH.

HIV (human immunodeficiency virus) infection is today a very important health issue worldwide, which demands new ways and strategies for its prevention and treatment. Several studies on the innate immunity against HIV infection have shown that antimicrobial peptides are associated with increased resistance to infection. In the present review, we briefly summarize the major characteristics of antimicrobial peptides from human and several species of plants, amphibians, insects and other animal species that have significant potential to be used as therapeutic or prophylactic agents. The mechanisms of infection inhibition and viral replication blockade are also described in the context of the biology of infection.