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Breast cancer (BC) and cardiometabolic diseases share a multifactorial and modifiable etiology, modulated by complex molecular pathways. Glutathione S-transferase (GST) plays a critical role, providing protection against xenobiotics and regulating levels of enzymes and proteins in the cell. GST variants have a significant impact on susceptibility to diseases whose pathogenesis involves oxidative stress, as is the case in many inflammatory diseases such as BC and cardiometabolic pathologies. However, the expression of these polymorphic variants has not been studied in BC. This study aimed to evaluate the presence of GST mRNA isoforms and their association with clinical and cardiometabolic parameters in women with BC. This was a case-control study, and a total of 57 participants were recruited. Concentrations of glucose and lipids in blood were measured in all the participants. GST variants (GSTT1, GSTM1 and GSTP1 Ile105Val polymorphism) were evaluated in all the participants by real-time PCR analysis. There was a significant association (p < 0.05) between the frequency of GSTP1 and LDL-c in the BC group. However, the control group showed significant associations between blood pressure with GSTT1 and GSTP1 variants with total cholesterol (TC), LDL-c, VLDL-c and triacylglycerols (TG). Therefore, GSTT1 and GSTP1 variants could be emerging biomarkers to discriminate between BC cases related or not to cardiometabolic disease factors.

Although COVID-19 in pregnant women and their neonates has been demonstrated, there is not enough evidence about how this vertical transmission occurs. This report describes a SARS-CoV-2 infection in a 21-year-old mother-daughter duo at the time of birth, focusing on the viral RNA detection in the stool of both and the human breast milk.

[Purpose] This article analyzes the Colombian Artificial Intelligence (AI) Strategy and seeks to answer the formulation process of Colombia’s digital transformation and Artificial Intelligence strategy. [Methodology/approach/design] The study utilizes a case study analysis approach to explore factors that may have influenced the Colombian AI policy formulation process. We conducted an elite interview and documentary research on public policy documents. [Findings]. This study identifies the inherent challenges of the national strategy for artificial intelligence. The implementation of the Colombian AI Strategy is guided by a market-oriented state model that promotes self-regulation regarding AI. [Practical implications] National strategies are an increasingly important theme of scholarly debate in AI policy. This article aims to contribute to analyzing such strategies, including the challenges inherent in their design and implementation. [Originality/value] This article examines how Latin America’s third most populous country, Colombia, shapes AI governance strategies. The uniqueness of this study lies in its proposition to outline the model of AI governance based on a detailed analysis of public policies.

Adobe is a traditional construction technique found in historic and new construction throughout the world, often in earthquake-prone regions. Adobe structures are particularly susceptible to seismic forces due to their substantial mass and low tensile capacity. In addition, adobe is affected negatively by moisture that may penetrate from the ground or through the plaster. This paper describes the preliminary findings of an experimental program to investigate the effect of higher water content in the lower part of the wall on the wall strength behaviour under lateral loading. Lateral load tests were conducted on two quarter-scale adobe walls, one in air-dry condition (Wall 1) and another with greater water content in the lower part (Wall 2). The model walls demonstrated similar behaviour during loading in terms of deflections; however, the higher water content in the lower part had a significant effect on the wall strength. The in-plane (lateral) load capacity of Wall 2 was approximately 74% of the capacity of Wall 1.

We introduce a new approach for modeling multivariate overdispersed binomial data, from a plant pathogen complex. After recalling some theoretical foundations of generalized linear models (GLMs) and Copula functions, we show how the later can be used to model correlated observations and overdispersed data. We illustrate this approach using fungal incidence in vegetables, which we analyzed using Gaussian copula with Beta-binomial margins. Compared to classical and generalized linear models, the model using Gaussian copula function best controls for overdispersion, being less prone to the underestimation of standard errors, the major cause of wrong inference in the statistical analysis of plant pathogen complex.

We introduce a new approach for modeling multivariate overdispersed binomial data, from a plant pathogen complex. After recalling some theoretical foundations of generalized linear models (GLMs) and Copula functions, we show how the later can be used to model correlated observations and overdispersed data. We illustrate this approach using fungal incidence in vegetables, which we analyzed using Gaussian copula with Beta-binomial margins. Compared to classical and generalized linear models, the model using Gaussian copula function best controls for overdispersion, being less prone to the underestimation of standard errors, the major cause of wrong inference in the statistical analysis of plant pathogen complex.Se introduce un nuevo enfoque para modelar datos binomiales multivariados con sobredispersión, obtenidos de complejos de patógenos vegetales. Después de revisar los conceptos básicos de los modelos lineales generalizados (GLMs) y las funciones Cópula, se muestra cómo estas últimas pueden usarse para modelar observaciones correlacionadas y datos con sobredispersión. Se ilustra el método usando la incidencia de hongos en hortalizas, analizando el caso por medio de la función cópula Gaussiana con marginales Beta-binomiales. Comparado con los modelos lineales clásicos y generalizados, el modelo construido con la cópula Gaussiana es el que mejor controla la sobredispersión, siendo menos propenso a la subestimación de los errores estándar, la causa más importante de inferencia inapropiada en el análisis estadístico de complejos de patógenos vegetales.

Abstract Background Assessing measurement error in alveolar recruitment on computed tomography (CT) is of paramount importance to select a reliable threshold identifying patients with high potential for alveolar recruitment and to rationalize positive end-expiratory pressure (PEEP) setting in acute respiratory distress syndrome (ARDS). The aim of this study was to assess both intra- and inter-observer smallest real difference (SRD) exceeding measurement error of recruitment using both human and machine learning-made lung segmentation (i.e., delineation) on CT. This single-center observational study was performed on adult ARDS patients. CT were acquired at end-expiration and end-inspiration at the PEEP level selected by clinicians, and at end-expiration at PEEP 5 and 15 cmH2O. Two human observers and a machine learning algorithm performed lung segmentation. Recruitment was computed as the weight change of the non-aerated compartment on CT between PEEP 5 and 15 cmH2O. Results Thirteen patients were included, of whom 11 (85%) presented a severe ARDS. Intra- and inter-observer measurements of recruitment were virtually unbiased, with 95% confidence intervals (CI95%) encompassing zero. The intra-observer SRD of recruitment amounted to 3.5 [CI95% 2.4–5.2]% of lung weight. The human–human inter-observer SRD of recruitment was slightly higher amounting to 5.7 [CI95% 4.0–8.0]% of lung weight, as was the human–machine SRD (5.9 [CI95% 4.3–7.8]% of lung weight). Regarding other CT measurements, both intra-observer and inter-observer SRD were close to zero for the CT-measurements focusing on aerated lung (end-expiratory lung volume, hyperinflation), and higher for the CT-measurements relying on accurate segmentation of the non-aerated lung (lung weight, tidal recruitment…). The average symmetric surface distance between lung segmentation masks was significatively lower in intra-observer comparisons (0.8 mm [interquartile range (IQR) 0.6–0.9]) as compared to human–human (1.0 mm [IQR 0.8–1.3] and human–machine inter-observer comparisons (1.1 mm [IQR 0.9–1.3]). Conclusions The SRD exceeding intra-observer experimental error in the measurement of alveolar recruitment may be conservatively set to 5% (i.e., the upper value of the CI95%). Human–machine and human–human inter-observer measurement errors with CT are of similar magnitude, suggesting that machine learning segmentation algorithms are credible alternative to humans for quantifying alveolar recruitment on CT.

Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immunosuppressive microenvironments, and leukemic stem cell populations elusive to immune recognition and destruction. While there are promising T cell-based therapies including chimeric antigen receptor (CAR)-T designs under development, other cytotoxic lymphocyte cell subsets have unique phenotypes and capabilities that might be of additional benefit in AML treatment. Of particular interest are the natural killer (NK) and unconventional T cells known as invariant natural killer T (iNKT) and gamma delta (γδ) T cells. NK, iNKT, and γδT cells exhibit intrinsic anti-malignant properties, potential for alloreactivity, and human leukocyte-antigen (HLA)-independent function. Here we review the biology of each of these unconventional cytotoxic lymphocyte cell types and compare and contrast their strengths and limitations as the basis for adoptive cell therapies for AML.

Abstract Background PEEP selection in severe COVID-19 patients under extracorporeal membrane oxygenation (ECMO) is challenging as no study has assessed the alveolar recruitability in this setting. The aim of the study was to compare lung recruitability and the impact of PEEP on lung aeration in moderate and severe ARDS patients with or without ECMO, using computed tomography (CT). Methods We conducted a two-center prospective observational case–control study in adult COVID-19-related patients who had an indication for CT within 72 h of ARDS onset in non-ECMO patients or within 72 h after ECMO onset. Ninety-nine patients were included, of whom 24 had severe ARDS under ECMO, 59 severe ARDS without ECMO and 16 moderate ARDS. Results Non-inflated lung at PEEP 5 cmH2O was significantly greater in ECMO than in non-ECMO patients. Recruitment induced by increasing PEEP from 5 to 15 cmH2O was not significantly different between ECMO and non-ECMO patients, while PEEP-induced hyperinflation was significantly lower in the ECMO group and virtually nonexistent. The median [IQR] fraction of recruitable lung mass between PEEP 5 and 15 cmH2O was 6 [4–10]%. Total superimposed pressure at PEEP 5 cmH2O was significantly higher in ECMO patients and amounted to 12 [11–13] cmH2O. The hyperinflation-to-recruitment ratio (i.e., a trade-off index of the adverse effects and benefits of PEEP) was significantly lower in ECMO patients and was lower than one in 23 (96%) ECMO patients, 41 (69%) severe non-ECMO patients and 8 (50%) moderate ARDS patients. Compliance of the aerated lung at PEEP 5 cmH2O corrected for PEEP-induced recruitment (CBABY LUNG) was significantly lower in ECMO patients than in non-ECMO patients and was linearly related to the logarithm of the hyperinflation-to-recruitment ratio. Conclusions Lung recruitability of COVID-19 pneumonia is not significantly different between ECMO and non-ECMO patients, with substantial interindividual variations. The balance between hyperinflation and recruitment induced by PEEP increase from 5 to 15 cmH2O appears favorable in virtually all ECMO patients, while this PEEP level is required to counteract compressive forces leading to lung collapse. CBABY LUNG is significantly lower in ECMO patients, independently of lung recruitability.

Abstract Background Personalizing mechanical ventilation requires the development of reliable bedside monitoring techniques. The multiple-breaths nitrogen washin–washout (MBNW) technique is currently available to measure end-expiratory lung volume (EELVMBNW), but the precision of the technique may be poor, with percentage errors ranging from 28 to 57%. The primary aim of the study was to evaluate the reliability of a novel MBNW bedside system using fast mainstream sensors to assess EELV in an experimental acute respiratory distress syndrome (ARDS) model, using computed tomography (CT) as the gold standard. The secondary aims of the study were: (1) to evaluate trending ability of the novel system to assess EELV; (2) to evaluate the reliability of estimated alveolar recruitment induced by positive end-expiratory pressure (PEEP) changes computed from EELVMBNW, using CT as the gold standard. Results Seven pigs were studied in 6 experimental conditions: at baseline, after experimental ARDS and during a decremental PEEP trial at PEEP 16, 12, 6 and 2 cmH2O. EELV was computed at each PEEP step by both the MBNW technique (EELVMBNW) and CT (EELVCT). Repeatability was assessed by performing replicate measurements. Alveolar recruitment between two consecutive PEEP levels after lung injury was measured with CT (VrecCT), and computed from EELV measurements (VrecMBNW) as ΔEELV minus the product of ΔPEEP by static compliance. EELVMBNW and EELVCT were significantly correlated (R 2 = 0.97). An acceptable non-constant bias between methods was identified, slightly decreasing toward more negative values as EELV increased. The conversion equation between EELVMBNW and EELVCT was: EELVMBNW = 0.92 × EELVCT + 36. The 95% prediction interval of the bias amounted to ± 86 mL and the percentage error between both methods amounted to 13.7%. The median least significant change between repeated measurements amounted to 8% [CI95%: 4–10%]. EELVMBNW adequately tracked EELVCT changes over time (concordance rate amounting to 100% [CI95%: 87%–100%] and angular bias amounting to − 2° ± 10°). VrecMBNW and VrecCT were significantly correlated (R 2 = 0.92). A non-constant bias between methods was identified, slightly increasing toward more positive values as Vrec increased. Conclusions We report a new bedside MBNW technique that reliably assesses EELV in an experimental ARDS model with high precision and excellent trending ability.

Objective:The standard treatment for complicated Stanford type B aortic dissection (TBAD) is thoracic endovascular aortic repair (TEVAR). Functional parameters, specifically blood flow, are not measured in the clinical assessment of TEVAR, yet they are of outmost importance in patient outcome. Consequently, we investigated the impact of TEVAR on the flows in the aorta and its branches in TBAD using 4D Phase-Contrast Magnetic Resonance Imaging (4D Flow MRI).MethodsSeven patients with TBAD scheduled for TEVAR underwent pre and post-operative 4D Flow MRI. An experienced reader assessed the presence of helical flow in the false lumen (FL) using streamlines and measured net flow at specific locations. In addition, forward and reverse flows, stasis, helicity, and absolute helicity were computed automatically along the aorta centerline. Average values were then computed in the segmented vessels. Impact of TEVAR on these parameters was assessed with a Wilcoxon signed rank test. Impact of the metallic stent on the velocity quantification was assessed using intra-class correlation coefficient (ICC) between velocities measured intra-stent and in adjacent stent-free regions.ResultsFL helical flow was observed proximally in 6 cases and distally in 2 cases pre-operatively. Helical flow disappeared post-TEVAR proximally, but developed distally for 2 patients. Intra-stent measures were similar to stent-free with a median difference of 0.1 L/min and an ICC equal to 0.967 (p < 0.01). Forward flow increased from 59.9 to 81.6% in the TL and significantly decreased in the FL from 15.9 to 3.3%. Similarly, reverse flow increased in the TL from 4.36 to 10.8% and decreased in the FL from 10.3 to 4.6%. No significant changes were observed in net flow for aortic branches (p > 0.05). A significant increase in FL stasis was observed (p = 0.04).DiscussionTEVAR significantly increased forward flow in the TL and significantly decreased both forward and reverse flows in the FL. Interestingly, reverse flow in the TL increased post-TEVAR, which could be due to increased rigidity of the wall, due to the metallic stent. User independent helicity quantification enabled detection of elevated helicity at the level of secondary entry tears which had been missed by streamline visualization.

Adoptively transferred T cell-based cancer therapies have shown incredible promise in treatment of various cancers. So far therapeutic strategies using T cells have focused on manipulation of the antigen-recognition machinery itself, such as through selective expression of tumor-antigen specific T cell receptors or engineered antigen-recognition chimeric antigen receptors (CARs). While several CARs have been approved for treatment of hematopoietic malignancies, this kind of therapy has been less successful in the treatment of solid tumors, in part due to lack of suitable tumor-specific targets, the immunosuppressive tumor microenvironment, and the inability of adoptively transferred cells to maintain their therapeutic potentials. It is critical for therapeutic T cells to overcome immunosuppressive environmental triggers, mediating balanced antitumor immunity without causing unwanted inflammation or autoimmunity. To address these hurdles, chimeric receptors with distinct signaling properties are being engineered to function as allies of tumor antigen-specific receptors, modulating unique aspects of T cell function without directly binding to antigen themselves. In this review, we focus on the design and function of these chimeric non-antigen receptors, which fall into three broad categories: ‘inhibitory-to-stimulatory’ switch receptors that bind natural ligands, enhanced stimulatory receptors that interact with natural ligands, and synthetic receptor-ligand pairs. Our intent is to offer detailed descriptions that will help readers to understand the structure and function of these receptors, as well as inspire development of additional novel synthetic receptors to improve T cell-based cancer therapy.

COVID-19 is a severe respiratory disease threatening pregnant women, which increases the possibility of adverse pregnancy outcomes. Several recent studies have demonstrated the ability of SARS-CoV-2 to infect the mother enterocytes, disturbing the gut microbiota diversity. The aim of this study was to characterize the entero-mammary microbiota of women in the presence of the virus during delivery. Fifty mother–neonate pairs were included in a transversal descriptive work. The presence of SARS-CoV-2 RNA was detected in nasopharyngeal, mother rectal swabs (MRS) and neonate rectal swabs (NRS) collected from the pairs, and human colostrum (HC) samples collected from mothers. The microbiota diversity was characterized by high-throughput DNA sequencing of V3-16S rRNA gene libraries prepared from HC, MRS, and NRS. Data were analyzed with QIIME2 and R. Our results indicate that several bacterial taxa are highly abundant in MRS positive for SARS-CoV-2 RNA. These bacteria mostly belong to the Firmicutes phylum; for instance, the families Bifidobacteriaceae, Oscillospiraceae, and Microbacteriaceae have been previously associated with anti-inflammatory effects, which could explain the capability of women to overcome the infection. All samples, both positive and negative for SARS-CoV-2, featured a high abundance of the Firmicutes phylum. Further data analysis showed that nearly 20% of the bacterial diversity found in HC was also identified in MRS. Spearman correlation analysis highlighted that some genera of the Proteobacteria and Actinobacteria phyla were negatively correlated with MRS and NRS (p < 0.005). This study provides new insights into the gut microbiota of pregnant women and their potential association with a better outcome during SARS-CoV-2 infection.

T cell-based immunotherapies including genetically engineered T cells, adoptive transfer of tumor-infiltrating lymphocytes, and immune checkpoint blockade highlight the impressive anti-tumor effects of T cells. These successes have provided new hope to many cancer patients with otherwise poor prognoses. However, only a fraction of patients demonstrates durable responses to these forms of therapies and many develop significant immune-mediated toxicity. These heterogeneous clinical responses suggest that underlying nuances in T cell genetics, phenotypes, and activation states likely modulate the therapeutic impact of these approaches. To better characterize known genetic variations that may impact T cell function, we 1) review the function of early T cell receptor-specific signaling mediators, 2) offer a synopsis of known mutations and genetic alterations within the associated molecules, 3) discuss the link between these mutations and human disease and 4) review therapeutic strategies under development or in clinical testing that target each of these molecules for enhancing anti-tumor T cell activity. Finally, we discuss novel engineering approaches that could be designed based on our understanding of the function of these molecules in health and disease.

Semaphorin 4D (Sema4D) is a glycoprotein that is expressed by several tumors and immune cells. It can function as a membrane bound protein or as a cleaved soluble protein (sSema4D). We sought to investigate the translational potential of plasma sSema4D as an immune marker in plasma of patients with head and neck squamous cell carcinoma (HNSCC). Paired peripheral blood and tumor tissue samples of 104 patients with HNSCC were collected at the same time point to allow for real time analysis. Scoring of the histological inflammatory subtype (HIS) was carried out using Sema4D immunohistochemistry on the tumor tissue. sSema4D was detected in plasma using direct ELISA assay. Defining elevated sSema4D as values above the 95th percentile in healthy controls, our data showed that sSema4D levels in plasma were elevated in 25.0% (95% CI, 16.7–34.9%) of the patients with HNSCC and showed significant association with HIS immune excluded (HIS-IE) (p = 0.007), Sema4D+ve tumor cells (TCs) (p = 0.018) and PD-L1+ve immune cells (ICs) (p = 0.038). A multi-variable logistic regression analysis showed that HIS was significantly (P = 0.004) associated with elevated sSema4D, an association not explained by available patient-level factors. Using the IO-360 nanoString platform, differential gene expression (DGE) analysis of 10 HNSCC tumor tissues showed that patients with high sSema4D in plasma (HsS4D) clustered as IFN-γ negative tumor immune signature and were mostly HIS-IE. The IC type in the HsS4D paired tumor tissue was predominantly myeloid, while the lymphoid compartment was higher in the low sSema4D (LsS4D). The Wnt signaling pathway was upregulated in the HsS4D group. Further analysis using the IO-360, 770 gene set, showed significant non-inflamed profile of the HsS4D tumors compared to the LsS4D. In conclusion, our data reveals an association between sSema4D and the histological inflammatory subtype.

Over the past decade, immunotherapies have revolutionized the treatment of cancer. Although the success of immunotherapy is remarkable, it is still limited to a subset of patients. More than 1500 clinical trials are currently ongoing with a goal of improving the efficacy of immunotherapy through co-administration of other agents. Preclinical, small-animal models are strongly desired to increase the pace of scientific discovery, while reducing the cost of combination drug testing in humans. Human immune system (HIS) mice are highly immune-deficient mouse recipients rtpeconstituted with human hematopoietic stem cells. These HIS-mice are capable of growing human tumor cell lines and patient-derived tumor xenografts. This model allows rapid testing of multiple, immune-related therapeutics for tumors originating from unique clinical samples. Using a cord blood-derived HIS-BALB/c-Rag2nullIl2rγnullSIRPαNOD (BRGS) mouse model, we summarize our experiments testing immune checkpoint blockade combinations in these mice bearing a variety of human tumors, including breast, colorectal, pancreatic, lung, adrenocortical, melanoma and hematological malignancies. We present in-depth characterization of the kinetics and subsets of the HIS in lymph and non-lymph organs and relate these to protocol development and immune-related treatment responses. Furthermore, we compare the phenotype of the HIS in lymph tissues and tumors. We show that the immunotype and amount of tumor infiltrating leukocytes are widely-variable and that this phenotype is tumor-dependent in the HIS-BRGS model. We further present flow cytometric analyses of immune cell subsets, activation state, cytokine production and inhibitory receptor expression in peripheral lymph organs and tumors. We show that responding tumors bear human infiltrating T cells with a more inflammatory signature compared to non-responding tumors, similar to reports of “responding” patients in human immunotherapy clinical trials. Collectively these data support the use of HIS mice as a preclinical model to test combination immunotherapies for human cancers, if careful attention is taken to both protocol details and data analysis.

Abstract Glioma is a unique neoplastic disease that develops exclusively in the central nervous system (CNS) and rarely metastasizes to other tissues. This feature strongly implicates the tumor-host CNS microenvironment in gliomagenesis and tumor progression. We investigated the differences and similarities in glioma biology as conveyed by transcriptomic patterns across four mammalian hosts: rats, mice, dogs, and humans. Given the inherent intra-tumoral molecular heterogeneity of human glioma, we focused this study on tumors with upregulation of the platelet-derived growth factor signaling axis, a common and early alteration in human gliomagenesis. The results reveal core neoplastic alterations in mammalian glioma, as well as unique contributions of the tumor host to neoplastic processes. Notable differences were observed in gene expression patterns as well as related biological pathways and cell populations known to mediate key elements of glioma biology, including angiogenesis, immune evasion, and brain invasion. These data provide new insights regarding mammalian models of human glioma, and how these insights and models relate to our current understanding of the human disease.

Myeloid-derived suppressor cells (MDSCs) inhibit T cell responses and are relevant to cancer, autoimmunity and transplant biology. Anti-thymocyte globulin (ATG) is a commonly used T cell depletion agent, yet the effect of ATG on MDSCs has not been investigated. MDSCs were generated in Lewis Lung Carcinoma 1 tumor-bearing mice. MDSC development and function were assessed in vivo and in vitro with and without ATG administration. T cell suppression assays, RT-PCR, flow cytometry and arginase activity assays were used to assess MDSC phenotype and function. MDSCs increased dramatically in tumor-bearing mice and the majority of splenic MDSCs were of the polymorphonuclear subset. MDSCs potently suppressed T cell proliferation. ATG-treated mice developed 50% fewer MDSCs and these MDSCs were significantly less suppressive of T cell proliferation. In vitro , ATG directly bound 99.6% of MDSCs. CCR7, L-selectin and LFA-1 were expressed by both T cells and MDSCs, and binding of LFA-1 was inhibited by ATG pre-treatment. Arg-1 and PD-L1 transcript expression were reduced 30–40% and arginase activity decreased in ATG-pretreated MDSCs. MDSCs were bound and functionally inhibited by ATG. T cells and MDSCs expressed common Ags which were also targets of ATG. ATG may be helpful in tumor models seeking to suppress MDSCs. Alternatively, ATG may inadvertently inhibit important T cell regulatory events in autoimmunity and transplantation.

Quinacrine (Qx), a molecule used as an antimalarial, has shown anticancer, antiprion, and antiviral activity. The most relevant antiviral activities of Qx are related to its ability to raise pH in acidic organelles, diminishing viral enzymatic activity for viral cell entry, and its ability to bind to viral DNA and RNA. Moreover, Qx has been used as an immunomodulator in cutaneous lupus erythematosus and various rheumatological diseases, by inhibiting phospholipase A2 modulating the Th1/Th2 response. The aim of this study was to evaluate the potential antiviral effect of Qx against denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Vero E6 cells. The cytotoxicity of Qx in Vero E6 cells was determined by the MTT assay. Afterwards, Vero E6 cells were infected with SARS-CoV-2 at different multiplicities of infections (MOIs) of 0.1 and 0.01 in the presence of Qx (0–30 µM) to determinate the half maximal effective concentration (EC50). After 48 h, the effect of Qx against SARS-CoV-2 was assessed by viral cytotoxicity and viral copy numbers, the last were determined by digital real-time RT-PCR (ddRT-PCR). Additionally, electron and confocal microscopy of Vero E6 cells infected and treated with Qx was studied. Our data show that Qx reduces SARS-CoV-2 virus replication and virus cytotoxicity, apparently by inhibition of viral ensemble, as observed by ultrastructural images, suggesting that Qx could be a potential drug for further clinical studies against coronavirus disease 2019 (COVID-19) infection.

La innovación tiende a mejorar el proceso productivo dentro de una empresa, aquello que pueda ser más atractivo y presentable, que proporcione cambios e introduzca novedades para lograr los objetivos y metas planteadas. En el contexto actual es necesario el estímulo al cambio. Este trabajo investigativo se enfocó en determinar la influencia de la innovación en el proceso productivo de la estación de servicios Inés Galeano, en el periodo 2018. Para realizar este tipo de estudio se tomó en cuenta la metodología, que consiste en buscar las fuentes más creíbles como es la Bibliografía en la Biblioteca Urania Zelaya, FAREM-Estelí, Libros, tesis relacionadas con el tema, libros en la página web. Se analizó el impacto que han tenido las mejoras aplicadas a los elementos más importantes de los procesos de trabajo que se realizan en la organización, en los servicios que se ofertan. Es una investigación aplicada, de carácter descriptivo y se enmarca metodológicamente en un enfoque mixto y de corte transversal. La muestra la constituyeron los 22 colaboradores que forman parte de la empresa. Para la recolección de esta información, fue necesaria la utilización de instrumentos como encuestas y entrevistas, la cual sirvió como base para conocer los problemas existentes en dicho lugar. Este estudio se basó en el supuesto el cual sugiere que la innovación, contribuye al proceso productivo de la empresa. Los principales resultados se enfocan en lo siguiente: se establece la influencia de la innovación en el proceso productivo, es decir de qué manera han aportado los cambios innovadores en los procesos de trabajo de la empresa y se describe las innovaciones en los aspectos más relevantes de sus servicios, así como se identificaron los beneficios de las mejoras aplicadas en los aspectos más relevantes de la organización.

Edgar Calel (1987) é um artista Maya kaqchikel da Guatemala. Sua prática artística, pautada pela mobilidade e pelo movimento, lida com temas ligados à migração, ao deslocamento e ao retorno. Originário de Comalapa, Calel saiu de sua cidade natal para estudar arte, fazendo de sua vida uma jornada. Neste ensaio visual são apresentados registros de algumas séries como Yo vivo en ti, Tú vives en mi; B ́atz – tejido constelación de saberes; Ixim (Maíz); e Laberinto de los Pájaros. O ensaio se encerra com o texto Memoria del movimiento, de Sebastián Eduardo [Dávila].

The spatial distribution of Colombobalanus excelsa forests in the Cueva de los Guácharos Natural National Park and its buffer zone was determined. The forest’s structural parameters were determined by conducting a stratified forest inventory that consisted of four plots of 0.5 ha distributed in two strata. The first stratum was located in the park and the second in its buffer zone. Each strip consisted of plots of 20 x 50 m within which individuals with diameters at breast height = 10 cm DBH were measured for total height, crown diameter and the condition of each tree. Within each strip a 10 x 10 m subplot was used to assess individuals with DBH = 10 cm and heights greater than 3 m. In addition the number of seedlings of height = 0.3 m were counted in subplots of 5 x 5 m. Models were generated to estimate the height and volume as a function of DBH. We report a total of eight natural stands of black oak reaching 2000 ha of which 28.3 ha were found within the park. We report a density of 281.7 trees ha-1 with a basal area of 52.33 m2 ha-1 and a volume of 761.65 m3 ha-1. The form-factor for the species was of 0.76041. Six models were fitted to estimate the height and six for volume adjustments of 0.90 and 0.988, respectively.